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W O Whetsell

Publications and source records attributed to W O Whetsell.

At least 19 recordsLinked to original sources
PubMed1992

Preferential loss of striato-external pallidal projection neurons in presymptomatic Huntington's disease.

We have reported previously that striatal projection neurons are differentially affected in the course of Huntington's disease, and in a prior patient report we noted that differential loss of striatal projection neurons occurs also in patients with presymptomatic Huntington's disease. Striatal neurons projecting to the external segment of the globus pallidus or the substantia nigra show evident loss, whereas those projecting to the internal segment of the globus pallidus appear relatively spared at presymptomatic and early stages of symptomatic Huntington's disease. We now report similar findings in a second apparently presymptomatic Huntington's disease allele carrier.

Adult↗
PubMed1992

Distribution of Alzheimer's disease-associated protein (ADAP) in 10 human brains.

ALZ50-based enzyme immunoassay was used to study distribution of Alzheimer's disease-associated protein (ADAP) in postmortem brain tissues of 5 Alzheimer's disease (AD) and 5 non-Alzheimer's disease (NAD) subjects. There are at least three AD-associated proteins, including A68. Levels are higher in brain regions with severe neuronal loss in AD: frontal, temporal, hippocampal cortex, and amygdala. No significant ADAP was found in the NAD samples (from 2 age-matched-1 clinically demented-and 3 younger subjects). ADAP levels in four regions of AD brains were not correlated to neuritic plaque count in corresponding regions of matching formaldehyde-fixed hemispheres.

Adult↗
PubMed1992

Cochleovestibular nerve compression syndrome. II. Vestibular nerve histopathology and theory of pathophysiology.

The present study was undertaken to systematically examine and characterize pathological changes in vestibular nerve specimens obtained at surgery in patients with symptomatic cochleovestibular nerve compression syndrome (CNCS). Vestibular nerves were obtained in six cases of CNCS and were intermingled with vestibular nerves obtained in cases of Meniere's disease. All of the nerve specimens were coded and reviewed microscopically in a blind-study fashion by the neuropathologist. The vestibular nerves obtained from CNCS cases showed significant endoneurial fibrosis, compared to controls (specimens from patients with Meniere's disease). Based on observations in this study, as well as the clinical symptoms and audiovestibular test findings in these patients, a theory of pathophysiology in CNCS of the cochleovestibular nerve is proposed. The implications of this theory are discussed with respect to the diagnosis of CNCS.

Axons↗
PubMed1991

Neurotrophic activity of S-100 beta in cultures of dorsal root ganglia from embryonic chick and fetal rat.

We report here that S-100 beta, a protein with neurotrophic activity on central nervous system neurons, stimulates neuritic outgrowth from cultures of dorsal root ganglia (DRG). S-100 beta elicited neurites from explant and dissociated cell cultures of embryonic chick DRG, and the extent of the response varied with the age of the embryo. Specificity was demonstrated by the observation that incubation of S-100 beta with antibodies directed against S-100 beta reduced the neurite outgrowth, whereas incubation of S-100 beta with normal rabbit serum had little effect. S-100 beta also stimulated the area of neuritic outgrowth from organotypic cultures of fetal rat DRG, showing that the activity of the protein is not restricted to a particular species or culture condition. A mutant S-100 beta lacking neurotrophic activity on cerebral cortex neurons was unable to effectively stimulate neurite outgrowth from DRG cultures. These studies suggest that S-100 beta may play a role in neuronal growth and/or maintenance in the peripheral nervous system.

Animals↗
PubMed1991

Immunohistochemical localization of quinolinic acid phosphoribosyltransferase in the human neostriatum.

The localization and distribution of quinolinic acid phosphoribosyltransferase, the degradative enzyme of the endogenous excitotoxin quinolinic acid, were studied in the post mortem human neostriatum by immunohistochemistry. In eight neurologically normal human brains, quinolinic acid phosphoribosyltransferase immunoreactivity was detected in both glial cells and neurons. Typically, glial cells containing quinolinic acid phosphoribosyltransferase immunoreactivity had numerous processes radiating from the cell bodies. In Nissl-counterstained sections, most quinolinic acid phosphoribosyltransferase-immunoreactive glial cells showed round, large and pale nuclei. These morphological features indicate that they are probably astrocytes. Neurons containing quinolinic acid phosphoribosyltransferase immunoreactivity had different sizes and shapes and were tentatively classified into three subpopulations. Most were medium-sized cells with ovoid or elongated perikarya. Small quinolinic acid phosphoribosyltransferase-immunoreactive neurons, often spheroid in shape, were particularly noted in a zone of the caudate nucleus adjacent to the lateral ventricle. A few large quinolinic acid phosphoribosyltransferase-positive neurons were also present in both the caudate and putamen. The somatic and dendritic morphology of quinolinic acid phosphoribosyltransferase-immunoreactive neurons closely resembles that of aspiny neurons seen in Golgi preparations. The localization of the specific quinolinic acid-catabolizing enzyme in distinct populations of neostriatal cells suggests specific functional correlates. It remains to be examined how the anatomical organization of quinolinic acid phosphoribosyltransferase immunoreactivity relates to the degradation of quinolinic acid in the striatum, and if the morphological characteristics and distribution of quinolinic acid phosphoribosyltransferase-immunoreactive cells are of relevance for the pathogenesis of neurodegenerative basal ganglia disorders.

Adult↗
PubMed1990

Distribution of quinolinic acid phosphoribosyltransferase in the human hippocampal formation and parahippocampal gyrus.

The morphological distribution of quinolinic acid phosphoribosyltransferase (QPRT), the degradative enzyme of the endogenous excitotoxin quinolinic acid, was studied in the human hippocampal formation and parahippocampal gyrus by immunohistochemical techniques. In seven neurologically normal human brains obtained at autopsy, QPRT-immunoreactivity (QPRT-i) was found in both glial cells and neurons. Glial cells exhibiting QPRT-immunoreactivity morphological features of astrocytes, were observed in all hippocampal subfields. The polymorphic layer of the dentate gyrus contained the highest density of QPRT-i glial cells. Numerous QPRT-i glial cells were also found along both sides of the fused hippocampal fissure and in the white matter including the alveus of Ammon's horn, whereas only a few were observed in the granule cell layer and the stratum pyramidale. Neurons containing QPRT-i were found mainly in the subiculum and in the strata oriens and pyramidale of CA1. They were mostly small and polymorphic or fusiform, thus indicating that they may belong to a subpopulation of interneurons. Moderate numbers of QPRT-i glial cells and neurons were also observed throughout layers II-VI of parahippocampal cortex. The localization of QPRT-i in selected glial cells and neurons suggests that in the regions examined these cellular elements might play specific roles in the regulation of quinolinic acid function.

Adult↗
PubMed1990

Fulminant monophasic multiple sclerosis, Marburg's type.

The clinical, neuroradiological and necropsy findings are described in a 49 year old woman with long-standing idiopathic pulmonary haemosiderosis and acute monophasic multiple sclerosis (Marburg's type). Progression of the demyelinating process produced blindness and paraplegia over three weeks. At five weeks, magnetic reasonance imaging (MRI) studies showed lesions in the pons and left occipital lobe. The patient died 10 weeks after onset of symptoms. Necropsy examination revealed acute plaques in the optic chiasm, and the white matter around the lateral and fourth ventricle and spinal cord. Similarities between this and previously described cases of Marburg's disease are discussed.

Axons↗
PubMed1989

Prolonged exposure to submicromolar concentrations of quinolinic acid causes excitotoxic damage in organotypic cultures of rat corticostriatal system.

Mature organotypic cultures of rat corticostriatal system (CXCA cultures) or caudate nucleus (CA cultures) were chronically exposed to 100 nM quinolinic acid (QUIN) for up to 7 weeks. Light and electron microscopic analysis showed no pathological changes in QUIN-exposed CA cultures or in control cultures incubated in regular feeding medium for this time period. In contrast, in CXCA cultures exposed to QUIN, there was focal degeneration characterized by the presence of vacuoles in neuropil, swollen dendrites, occasional swollen post-synaptic elements and degenerated neurons. Prolonged exposure to only slightly hyper-physiological concentrations of QUIN may cause neuronal death in slowly progressive neurodegenerative disorders such as Huntington's disease (HD).

Animals↗
PubMed1989

Alteration of kainic acid and quinolinic acid toxicity by neostriatal transplants in vitro.

Mature (greater than 21 days in vitro) organotypic corticostriatal cultures prepared from newborn rat brain were incubated in either kainic acid (KA) 10(-3) M or quinolinic acid (QUIN) 10(-3) M for up to 48 h. Other identical cultures were similarly incubated immediately after they had received one or two additional explants of neonatal striatal tissue placed beside each corticostriatal culture. The cultures incubated with either KA or QUIN in the presence of the neonatal striatal tissue showed better preservation than cultures incubated with KA or QUIN alone. Results suggest that the neonatal striatal explants or 'transplants' afford some protective effect against the toxicity or either KA or QUIN.

Animals↗
PubMed1989

Ultrastructural alterations induced by 1-methyl-4-phenylpyridinium (MPP+) in canine substantia nigra and rat mesencephalon in vitro.

Explants of canine substantia nigra (SN) and rat mesencephalon (MES), grown in organotypic culture, were incubated with 1-methyl-4-phenylpyridinium (MPP+) and examined for ultrastructural changes. Prolonged exposure (3 days) to doses ranging from 0.1 nM to 10 microM MPP+ resulted in total destruction of all constituents (neuronal and glial) of canine SN cultures. No association was noted between MPP+-induced toxicity and age of canine SN cultures. The first ultrastructural change observed in canine SN cultures incubated with 0.1 nM MPP+ was at 3 h. Grossly swollen mitochondria were noted in large nerve cells. Swollen mitochondria were present in all cells of canine SN cultures by 8 h of incubation with MPP+. Only those rat MES cultures with relatively high preincubation levels of homovanillac acid, determined as an index of viable dopaminergic neurons, incubated with MPP+ (10 microM) for up to 8 days exhibited ultrastructural changes, namely, a swelling of mitochondria within the cytoplasm of large nerve cells. These findings suggest that continual exposure to MPP+ in vitro results in a generalized, nonspecific toxicity in those species known to be susceptible to the parent compound 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in vivo. However, the initial ultrastructural change, i.e., a swelling of mitochondria, may be the same in all species regardless of sensitivity suggesting that the ultimate mechanism underlying MPP+-toxicity relates to mitochondrial function.

1-Methyl-4-phenylpyridinium↗
PubMed1989

Lipocortin-1 immunoreactivity in central and peripheral nervous system glial tumors.

We examined the cellular distribution of lipocortin-1 (L-1), a major physiologic substrate for the epidermal growth factor receptor/kinase, in 122 central nervous system (CNS) and peripheral nervous system (PNS) neoplasms using the peroxidase-antiperoxidase technique with a polyclonal antibody specific for L-1. Extensive L-1 immunoreactivity was demonstrated in many CNS tumors; in 11 of 21 glioblastoma multiformes, in five of 12 anaplastic astrocytomas, and in five of 14 astrocytomas. Significant numbers of immunoreactive ependymocytes or astrocytes were also seen in six of 13 ependymomas. In contrast, no immunostaining was detected in the oligodendrocytes in any of ten oligodendrogliomas. PNS tumors, found in two of five malignant nerve sheath tumors, 13 of 15 schwannomas, 13 of 17 neurofibromas, and 14 of 15 traumatic neuromas, also contained considerable L-1 immunoreactivity in Schwann cells or mast cells. These findings raise the possibility that L-1 may participate in the proliferation or subsequent differentiation of neoplastic astrocytes, ependymocytes, and Schwann cells.

Annexins↗
PubMed1989

Lipocortin-1 immunoreactivity in the normal human central nervous system and lesions with astrocytosis.

The authors have examined the cellular distribution of lipocortin-1 (L-1) in the normal and diseased central nervous system (CNS) using the peroxidase-antiperoxidase (PAP) technique with a polyclonal antibody specific for L-1. L-1 immunoreactivity was evaluated in the frontal cortex, parahippocampal gyrus/lateral ventricle, cerebellum, medulla, and spinal cord from 27 normal human fetuses, neonates, and adults without neurologic disease and in these same regions and representative lesions from 35 patients with diseases producing varying degrees of astrocytosis, including intraparenchymal hemorrhage; embolic, thrombotic, or traumatic infarctions; and Alzheimer's disease (AD). L-1 immunoreactivity was identified in ependymocytes, choroid plexus epithelia, and scattered subependymal astrocytes throughout the ventricular system from 15 weeks gestation through 82 years of age in both normal and diseased CNSs. L-1 immunoreactivity was also detected in reactive astrocytes and many macrophages surrounding each infarction regardless of site or pathogenesis and in scattered reactive astrocytes in people with AD or SDAT. The limited distribution of L-1 in CNS is consistent with the low amounts of L-1 found in brain and suggests that L-1 may participate in the normal function of ependymocytes and the pathophysiology of reactive astrocytosis.

Adult↗
PubMed1989

Osteoblastic meningioma of the fourth ventricle.

Meningiomas of the fourth ventricle are rare neoplasms. Only meningothelial and fibroblastic subtypes, purportedly arising from the tela choroidea, have been described. In this report we describe clinical, neuroradiological and pathological findings in a 52-year-old man with mild hydrocephalus produced by a large, calcified, osteoblastic meningioma of the fourth ventricle.

Cerebral Ventricles↗
PubMed1989

Mast cell and lymphoreticular infiltrates in neurofibromas. Comparison with nerve sheath tumors.

Cellular heterogeneity produced by non-Schwannian elements may distinguish neurofibromas from other Schwann cell neoplasma and contribute to a different tumor biology. The present study compared cell counts of mast cells, T and B lymphocytes, and macrophages in 32 neurofibromas with those in 27 schwannomas, 9 malignant nerve sheath tumors, and 17 traumatic neuromas. Immunohistochemical and histochemical analyses were performed on formalin-fixed, paraffin-embedded tissues using two monoclonal antibodies against B-lymphocyte epitopes (LN-1 and LN-2), one monoclonal antibody against T-lymphocyte epitopes (UCHL-1), one polyclonal antibody recognizing alpha 1-antichymotrypsin (ACT), a macrophage/histiocytemarker, and toluidine blue O stains. Neurofibromas contained relatively high concentrations of mast cells significantly greater than the concentrations in other neoplastic or reactive nerve sheath tumors. Most neurofibromas also displayed moderate concentrations of LN-2 immunoreactive cells, similar to the concentrations in traumatic neuromas and not statistically different from cell counts in other tumor types. Limited, variable LN-1 and UCHL-1 immunoreactive infiltrates were detected in neurofibromas and some peripheral schwannomas. Rare or moderate ACT immunoreactivity was detected in the majority of neurofibromas, in contrast with the absence, or rare appearance, of ACT immunostaining in cranial and peripheral nerve schwannomas and moderate numbers of immunoreactive cells in many malignant nerve sheath tumors. Mast cells are an important cellular marker of neurofibromas and may participate in the pathogenesis of these neoplasms.

Antibodies, Monoclonal↗
PubMed1988

Identification and quantification of kynurenic acid in human brain tissue.

Serial ion-exchange and high-performance liquid chromatography separations were employed for the tissue extraction and purification of kynurenic acid (KYNA). Subsequently, the compound isolated from postmortem human brain tissue was unequivocally identified as KYNA by nuclear magnetic resonance and mass spectrometric analyses. Regional distribution analyses revealed the highest concentration of KYNA (1.58 +/- 0.43 pmol/mg tissue) in the caudate nucleus with lower levels in the thalamus, globus pallidus, hippocampus, parietal cortex and frontal cortex. Of the brain structures examined, the lowest concentration of KYNA (0.14 +/- 0.02 pmol/mg tissue) was found in the cerebellum.

Aged↗
PubMed1988

Striatal grafts provide sustained protection from kainic and quinolinic acid-induced damage.

Grafts of neonatal striatal tissue were placed into the striata of adult rats. When challenged immediately with intrastriatal injections of either kainic or quinolinic acid, excitotoxic damage was prevented. Thirty days later these same graft recipients received another injection of excitotoxin. The intrastriatal grafts continued to mitigate toxin-induced damage. It is hypothesized that the grafted cells not only survive, but that they may continue to elaborate some substance or substances that prevent excitotoxin-induced injury for at least 30 days. Previous investigations indicated that grafts of neonatal striatal tissue can protect the recipient striatum from kainic acid toxicity. In the following study it is demonstrated that such grafts also protect the striatum from quinolinic acid, an endogenous excitotoxin which induces kainate-like neuronal degeneration and has been implicated in the pathogenesis of Huntington's disease. It is postulated that the salutary effect of striatal grafting may be sufficiently long lasting to mitigate a chronic toxic insult. Such grafting may therefore represent a therapy for Huntington's disease and other neurodegenerative disorders in which an endogenous or exogenous toxin has been implicated as the pathogenetic agent.

Animals↗