PubMed Health⌕ Search

Biomedical subjects

C Hulette

Publications and source records attributed to C Hulette.

At least 37 records · Page 2Linked to original sources
PubMed1997

Apolipoprotein E-epsilon 2 and Alzheimer's disease: genotype influences pathologic phenotype.

To determine whether apolipoprotein E epsilon 2 (APOE-epsilon 2) affects neuropathology in aging and Alzheimer's disease (AD), we compared beta-amyloid plaque (A beta P) and neurofibrillary tangle densities, neuropil thread formation, and amyloid angiopathy in five APOE-epsilon 2/3 AD patients, five APOE-epsilon 3/3 AD patients, five APOE-epsilon control patients, and five APOE-epsilon 3/3 control patients. We examined the (frontal and parietal) neocortex, hippocampus, entorhinal cortex, and cerebellum and found A beta P densities to be lower (t = 3.121, p = 0.011) in the cortex of APOE-epsilon 2/3 AD patients than in APOE-epsilon 3/3 AD patients. Amyloid angiopathy was also less in APOE-epsilon 2/3 patients than in APOE-3/3 patients (U = 4.500, p = 0.027). Control APOE-epsilon 2/3 brains had little AD-related pathology; even our 102-year-old control case showed few A beta Ps compared with the elderly APOE-epsilon 3/3 cases. The APOE-epsilon 2/3 genotype may influence pathologic phenotype in some aged normal and AD populations.

Aged↗
PubMed1997

Clinical-neuropathologic findings in multi-infarct dementia: a report of six autopsied cases.

To clarify the neuropathologic criteria for the diagnosis of vascular dementia principally caused by large-vessel cerebral infarction, we solicited autopsy cases of vascular dementia from 10 university neuropathology laboratories. We included only those cases with progressive dementia clinically diagnosed as Alzheimer's disease (AD) or multi-infarct dementia, in whom autopsy revealed only cerebral infarction, without significant neuropathologic features of AD or other neurodegenerative disorders. Only six cases, all men, met these criteria. Each of them had, for a year or longer, gradually increasing cognitive impairment sufficient to interfere with daily activities, without clear evidence of "stepwise" progression. The age of onset of dementia was 66 years or less in five of the six patients. The duration of dementia ranged from 2 to 14 years. Five of the six cases had a history of either cerebral ischemia or acute stroke with residual focal neurologic deficits. Only two were known to have hypertension. At autopsy severe atherosclerosis of the cerebral arteries was present in three cases; two of these had a thrombotic occlusion of one internal carotid artery and one had partial obstruction of other cerebral arteries. In five of six brains, gross infarctions were present involving the thalamus, caudate, putamen, or large portions of the frontal, parietal, and temporal lobes of one or both hemispheres. Vascular amyloid was absent in all but one of these five brains. In four cases, the dementia was clinically indistinguishable from AD except for a history of focal neurologic deficits. The difficulty encountered in finding large numbers of cases of VaD without coexisting neuropathologic evidence of AD suggests that "pure" vascular dementia is very uncommon.

Adult↗
PubMed1996

Morphological, biochemical, and genetic support for an apolipoprotein E effect on microtubular metabolism.

There are two distinct viewpoints on the association of the inheritance of apolipoprotein E (APOE) alleles and the age of onset distribution of Alzheimer's disease (AD): genetic and phenotypic expression. There have been multiple corroborations of the APOE-epsilon 4 association with Alzheimer's disease in populations around the world in clinic based studies as well as emerging epidemiological studies. The genetic data do not imply mechanism of pathogenesis. The phenotypic expression of AD has been based in theories based on amyloid plaques or neurofibrillary tangles. ApoE protein interacts with both beta-amyloid and tau in an isoform-specific manner. The interaction with tau had been thought to be an in vitro artifact, since apoE had not been previously localized to the neuronal cytoplasm. Immuno-EM studies have localized apoE in neuronal cytoplasm. ApoE3 interacts with both tau and MAP2c at the microtubule binding repeat domain under conditions in which apoE4 is less tightly bound. These data further support a hypothesis that apoE3 (and apoE2) protect the microtubule binding domain of tau from binding to itself to form paired helical filaments and neurofibrillary tangles, while protecting the site for microtubule stabilizing interactions with beta-tubulin. These data are supported by recent data from APOE knock-out mice demonstrating dendritic alterations leading to synaptic simplification similar to that observed in AD.

Age of Onset↗
PubMed1996

Ocular toxicity following high dose chemotherapy and autologous transplant.

A 49-year-old woman received an autologous transplant for breast cancer. Six weeks later she noticed visual disturbance of the left eye which correlated with a visual field abnormality. There was a milder degree of visual disturbance in the right eye. Treatment with high-dose steroids partially stabilized the problem, which was felt to be an ischemic optic neuropathy. She ultimately died of respiratory failure. Pathology of the optic nerves revealed demyelination. Visual disturbances following high-dose chemotherapy are uncommon; the pathology to date has not been elucidated. Steroid therapy may be useful.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

alpha 2-Adrenergic receptors in human spinal cord: specific localized expression of mRNA encoding alpha 2-adrenergic receptor subtypes at four distinct levels.

alpha 2-Adrenergic receptor (AR) subtype mRNA (alpha 2a, alpha 2b, alpha 2c) neuronal localization in human spinal cord has not been described. We therefore performed in situ hybridization to identify cell bodies at four levels of human spinal cord (cervical, thoracic, lumbar, sacral) containing alpha 2AR subtype specific mRNA. alpha 2AR mRNA is present in gray matter only (ventral > dorsal; sacral > cervical > thoracic = lumbar). In addition to alpha 2AR mRNA in cell bodies in thoracic and lumbar intermediolateral (sympathetic) and sacral intermediate (parasympathetic) cell columns (lamina VII), all levels in dorsal horn laminae I, II, V, and ventral horn lamina IX, we demonstrate alpha 2AR mRNA in dorsal horn laminae III and IV, and dorsal nucleus of Clarke, where alpha 2ARs have not been described. Previously unreported heterogeneity in alpha 2AR subtype distribution (alpha 2a and alpha 2bAR mRNA present, alpha 2cAR mRNA virtually absent) is found at all sites of alpha 2AR mRNA expression in human spinal cord, including locations known to mediate effects of alpha 2AR agonist drugs on nociception, autonomic function and motor tone. Cervical spinal cord demonstrates a predominance of alpha 2a mRNA signal, while thoracic, lumbar, and sacral spinal cord demonstrate an increasing predominance of alpha 2bAR mRNA. If confirmed at a protein level, these findings have profound implications for therapeutic strategies in managing human pain.

Autoradiography↗
PubMed1995

Fast spin-echo, magnetic resonance imaging-measured hippocampal volume: correlation with neuronal density in anterior temporal lobectomy patients.

To assess the value of magnetic resonance imaging (MRI)-measured hippocampal volume in the detection of hippocampal sclerosis, we studied 28 patients undergoing anterior temporal lobectomy for medically intractable mesial temporal lobe epilepsy. Hippocampal volumetry and visual analysis of T2 signal change were performed using fast spin-echo T2-weighed MRI. Quantitative neuronal density measurements were performed in the resected hippocampal specimens. There was a significant correlation between MRI-measured absolute hippocampal volume (AHV) and neuronal density in CA1, CA2, and CA3 subfields (p < 0.0001, p < 0.01, and p < 0.05, respectively). Differential hippocampal volume (side-to-side volume difference) failed to detect bilateral atrophy in three patients, but the bilateral hippocampal atrophy was recognized by considering AHV in these patients. This study suggests that MRI-measured AHV can be of value in elevating patients with mesial temporal lobe epilepsy, especially when there is no side-to-side difference in hippocampal volumetry.

Adolescent↗
PubMed1995

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part IX. A prospective cliniconeuropathologic study of Parkinson's features in Alzheimer's disease.

Although extrapyramidal signs such as rigidity, bradykinesia, and postural impairment frequently occur in patients with Alzheimer's disease (AD), the correlation of these parkinsonian manifestations with the neuropathologic changes of Parkinson's disease (PD) has not been well established. Previous clinicopathologic studies addressing this issue have been largely retrospective or have consisted of relatively small numbers of cases. We examined the neuropathologic correlates of clinical parkinsonism in 78 cases with autopsy-confirmed AD prospectively enrolled in the Consortium to Establish a Registry for Alzheimer's Disease. Sixteen (20.5%) of the 78 AD cases showed concomitant PD pathology (AD/PD) as evidenced by the presence of nigral degeneration and Lewy bodies at any site. There were neocortical Lewy bodies in eight of these 16 cases. Two or more clinical manifestations of extrapyramidal dysfunction were present in eight (50.0%) of the 16 cases of AD/PD versus 11 (17.7%) of the 62 cases of AD alone (p < 0.01). Although semiquantitative ratings of the frequency of neuritic plaques showed no differences between the two groups, neurofibrillary tangles in the AD/PD group were less frequent in the midfrontal (p < 0.001) and superior temporal cortex (p < 0.05). These findings support previous reports that AD/PD cases are more likely to manifest extrapyramidal dysfunction and show plaque predominance at autopsy.

Aged↗
PubMed1995

Influence of the susceptibility genes apolipoprotein E-epsilon 4 and apolipoprotein E-epsilon 2 on the rate of disease expressivity of late-onset Alzheimer's disease.

Apolipoprotein E-epsilon 4 (APOE4, gene; apoE4, protein) is a susceptibility gene or risk factor for Alzheimer's disease. The genetic relevance of APOE4 has been widely confirmed. The APOE gene is not a disease locus, with specific mutations causing Alzheimer disease. Allelic variations at the APOE locus affect the rate of disease progression. The association of specific inherited APOE alleles with age of onset distributions describes biological effects based on genotype. The inheritance of polymorphic genes with single amino acid differences between apoE4 and apoE3 (and between apoE3 and apoE2) at the protein level is associated with differences in the mean age of disease onset spanning almost two decades. The isoform-specific metabolism of apoE resulting in a faster rate of disease expression can now be studied with the expectation that genetically relevant processes are being investigated. There is now an opportunity to develop theories directed at the genetically relevant apoE metabolism that can significantly delay disease expression.

Age of Onset↗
PubMed1994

Apolipoprotein E is present in hippocampal neurons without neurofibrillary tangles in Alzheimer's disease and in age-matched controls.

Apolipoprotein E (apoE, protein; APOE, gene) is a susceptibility gene for late-onset familial and sporadic Alzheimer's disease (AD). To examine the role of apoE in the pathogenesis of AD, we used immunocytochemistry to compare apoE localization in the hippocampus of histologically confirmed cases of AD, Parkinson's disease (PD), and normal controls. We confirmed apoE immunoreactivity in astrocytes, senile plaques, blood vessels, and some neurons containing neurofibrillary tangles (NFTs). In addition, we observed apoE immunoreactivity in hippocampal neurons without NFTs in AD and PD patients as well as in some nondemented aged controls. In AD cases, apoE-immunoreactive neurites were closely associated with beta-amyloid (A beta) containing senile plaques and intraneuronal apoE was sometimes associated with immunoreactive tau protein accumulation. Thus, apoE is localized where it may affect the biological expression of two characteristic AD pathological correlates: extracellular A beta deposition and intraneuronal tau metabolism and NFT formation.

Aged↗
PubMed1994

The Haw River syndrome: dentatorubropallidoluysian atrophy (DRPLA) in an African-American family.

Haw River Syndrome (HRS) is a dominant neurodegenerative disease that has affected five generations of an African-American family in rural North Carolina. The disorder represents a unique spectrum of multiple system degenerations resembling Huntington's disease, spinocerebellar atrophy and dentatorubropallidoluysian atrophy (DRPLA), a neurodegenerative disease that has been primarily reported in Japan. Recently, DRPLA has been shown to be due to an expanded trinucleotide repeat located on chromosome 12pter-p12. We have genotyped this family and found HRS to be tightly linked to the DRPLA region. Further examination demonstrates that, despite their distinct cultural origins and clinical and pathological differences, HRS is caused by the same expanded CTG-B37 repeat as DRPLA.

Atrophy↗
PubMed1993

Nicotinic neuronal acetylcholine receptor alpha-3 subunit transcription in normal and myasthenic thymus.

Thymic transcription of the alpha-3 subunit of the AChR was studied through sequencing and PCR analysis of thymic cDNA clones, Northern blotting, and ribonuclease protection assays. This analysis revealed at least three, 3' end sequence variants for the alpha-3 subunit as well as a variant that results from the alternative splicing of an antisense 122 bp Alu sequence between exons 5 and 6 of the normal transcript. The spliced Alu sequence not only shifts the exon 6 reading frame but also carries an in-frame stop codon. If translated, this variant transcript would produce a truncated peptide lacking the fourth transmembrane domain of the subunit and carrying a carboxy terminus dodecapeptide not found in any other known AChR subunit sequence. The putative variant subunit may lack biological activity and should differ antigenically from its normal counterpart. In comparing the normal, the MG hypertrophic, and the MG thymoma for transcription of the alpha-3 subunit and its 122 bp variant, it was found that there were no qualitative or quantitative changes in alpha-3 transcript expression in the MG hypertrophic thymi. Thymomas, however, showed an overall decrease in alpha-3 transcription and a comparative increase in beta-amyloid precursor transcription. The decrease in the levels of alpha-3 transcription in thymomas may be related to the proliferation of thymic epithelial cells.

Amyloid beta-Protein Precursor↗
PubMed1989

Ataxia, chorea, seizures, and dementia. Pathologic features of a newly defined familial disorder.

Five generations of a family exhibit a unique autosomal dominant neurologic disorder characterized by the development (usually between 15 and 30 years of age) of ataxia, seizures, choreiform movements, progressive dementia, and death after 15 to 25 years of illness. Neuropathologic findings in two deceased family members revealed remarkably similar findings, including marked neuronal loss of the dentate nucleus, microcalcification of the globus pallidus, neuroaxonal dystrophy of the nucleus gracilis, and demyelination of the centrum semiovale. The clinical and pathologic findings are closely correlated. Ataxia and chorea are related to severe neuronal loss in the dentate nucleus with calcification in the globus pallidus. Dementia occurs with progressive demyelination of the centrum semiovale, and loss of posterior column function occurs with neuroaxonal dystrophy of the nucleus gracilis and nucleus cuneatus.

Adolescent↗
PubMed1985

Electron-dense deposits in extraglomerular vascular structures in IgA nephropathy. A retrospective study.

24 renal biopsies from 23 patients with IgA nephropathy (Berger's disease) were examined. This retrospective ultrastructural study focused on extraglomerular vascular structures since information about these structures in IgA nephropathy is lacking. Electron-dense deposits were observed in arterioles in 8 out of 18 biopsies (44%), in which arterioles were available for electron microscopic examination. Deposits were absent in peritubular capillaries and in all arteries. The presence of deposits had no correlation with the patient's blood pressure. The electron-dense deposits represent additional evidence that IgA nephropathy is a monosymptomatic form of a systemic disease that is mediated by circulating immune complexes of heterogeneous origin.

Adolescent↗
PubMedDate not supplied

Cortical alterations of angiotensin converting enzyme, angiotensin II and AT1 receptor in Alzheimer's dementia.

We investigated the immunohistochemical alterations of angiotensin converting enzyme (ACE), angiotensin II and AT1 receptor in the parietal cortex in Alzheimer's dementia (AD) to reveal the contributive role of the brain renin-angiotensin system in the disease process. In controls, ACE, angiotensin II and AT1 immunoreactivities were localized to pyramidal neurons of the cortex. The staining intensity was distinctly increased in AD for all three antigens, involving predominantly cortical layer V, which may reflect the enhanced brain renin-angiotensin system activity in the disease process. In addition, a prominent perivascular ACE and angiotensin II immunoreactivity surrounding some cortical vessels in aged controls and AD patients points to an underlying microvascular pathology in the process of neurodegeneration.

Aged↗
PubMedDate not supplied

Structure of the human sensorimotor system. I: Morphology and cytoarchitecture of the central sulcus.

We have studied the morphology of the central sulcus and the cytoarchitecture of the primary sensorimotor cortex in 20 human brains obtained at autopsy. Although the surface appearance of the central sulcus varies greatly from brain to brain (and between hemispheres of individual brains), its deep structure is remarkably consistent. The fundus of the central sulcus is divided into medial and lateral limbs by a complex junction midway between the sagittal and Sylvian fissures. Based on functional imaging studies, this junction appears to be a structural hallmark of the sensorimotor representation of the distal upper extremity. We also identified and measured area 4 (primary motor cortex) and area 3 (primary somatic sensory cortex) in Nissl-stained sections cut orthogonal to the course of the central sulcus. Although the positions of the cytoarchitectonic boundaries in the paracentral lobule showed considerable interindividual variation, the locations of the borders of areas 4 and 3 along the course of the sulcus were similar among the 40 hemispheres examined. In addition to describing more thoroughly this portion of the human cerebral cortex, these observations provide a basis for evaluating lateral symmetry of the human primary sensorimotor cortex.

Cerebral Cortex↗
PubMedDate not supplied

Structure of the human sensorimotor system. II: Lateral symmetry.

We have evaluated the lateral symmetry of the human central sulcus, brainstem and spinal cord using quantitative histological and imaging techniques in specimens from 67 autopsy cases. Our purpose was to determine whether the preferred use of the right hand in the majority of humans is associated with grossly discernible asymmetries of the neural centers devoted to the upper extremities. In the accompanying report, we described a consistent set of morphological features in the depths of the central sulcus that localize the sensorimotor representation of the distal upper extremity. Measurements of the cortical surface in this region, and indeed throughout the entire central sulcus, showed no average lateral asymmetry. Cytoarchitectonic measurements of area 4 and area 3 confirmed this similarity between the left and right hemispheres. The medullary pyramids, which contain the corticospinal tracts, were also symmetrical, as were the cross-sectional areas of white and gray matter in the cervical and lumbar enlargements of the spinal cord. Finally, we found no lateral difference in the size and number of motor neurons in the ventral horns at these levels of the cord. Based on these several observations, we conclude that the preferred use of the right hand in humans occurs without a gross lateral asymmetry of the primary sensorimotor system.

Adult↗