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Biomedical subjects

D R Hinton

Publications and source records attributed to D R Hinton.

At least 163 records · Page 9Linked to original sources
PubMed1989

Tumor necrosis factor identified in multiple sclerosis brain.

Frozen brain specimens from patients with multiple sclerosis (MS) and other neurologic diseases were analyzed using immunocytochemical techniques for the presence of TNF. In brain lesions in MS, and subacute sclerosing panencephalitis, TNF+ cells were demonstrated. At the lesion site in MS, TNF+ staining is associated with both astrocytes and macrophages. These observations were not made in Alzheimer's disease or normal brain tissue. The presence of TNF in MS lesions suggests a significant role for cytokines and the immune response in disease progression.

Astrocytes↗
PubMed1989

Howard Hughes Medical Institute and its role in genomic activities.

Through its three operating programs, the Howard Hughes Medical Institute has supported a substantial amount of basic and clinical molecular research, has acted as a facilitator in initiating and funding a number of meetings, nationally and internationally, including work groups dealing with databases, and has supported several databases for gene mapping. Finally, HHMI is now playing a significant national role in the training and development of manpower through its support of fellowships, direct grants to colleges and universities, and support for major teaching resources such as Woods Hole Marine Biology and Cold Spring Harbor Laboratories.

Academies and Institutes↗
PubMed1989

Heterotopic neurons in spinal cord of patients with ALS.

Monoclonal antibody 44.1, an immunocytochemical marker for neurons, identified heterotopically located, multipolar neurons deep within the spinal cord white matter of patients with amyotrophic lateral sclerosis. Displaced neurons were most numerous in the ventral outflow and lateral corticospinal tract regions of all cord levels. These changes may be the result of aberrant neuronal migration during spinal cord development.

Adult↗
PubMed1988

Monoclonal antibodies react with neuronal subpopulations in the human nervous system.

Monoclonal antibody probes were used to identify antigenic cross reactivities among neuronal subpopulations and to dissect the human nervous system at several levels of organization. Six monoclonal antibodies, prepared with immunogens from Drosophila melanogaster or human nervous tissue, were used to localize antigens immunocytochemically in normal adult human neocortex, hippocampus, cerebellum, spinal cord, and retina. Four of the six antibodies were neural specific in their reactivity and each stained a unique combination of neurons. The antibodies reacted with at least three subpopulations of cerebral cortical neurons, including discrete populations of pyramidal and nonpyramidal cells. Components of a widely distributed functional system within the spinal cord and cerebellum were labelled by one antibody, which reacted with neurons in the nucleus dorsalis of Clarke, deep cerebellar nuclei, and Purkinje cells. At the single-cell level, three of the monoclonals differentially labelled the photoreceptor cell outer segment, inner segment, and perikaryon. Three of the six antibodies were reactive with specific protein bands on immunoblots of tissue homogenates. This monoclonal antibody panel provides a novel and potentially useful method of analysis of the organization of the normal and diseased human nervous system.

Adult↗
PubMed1987

The sevenless+ protein is expressed apically in cell membranes of developing Drosophila retina; it is not restricted to cell R7.

In the sevenless (sev) mutants of Drosophila, a single cell type, photoreceptor R7, does not develop. We made monoclonal antibody against a sev+-beta-galactosidase fusion protein, and used it to determine the ultrastructural localization of the sev+ protein in the larval eye disc. The protein is expressed on the apical surface of the developing retina. It is not restricted to cell R7; it is expressed in all the presumptive photoreceptor cells, cone cells, and possibly others. The protein localizes to the cell membranes of the apical tips and their microvilli, away from the bulk of the cell-cell contacts. Possible mechanisms for generating the specificity of the sev phenotype are discussed in light of these results.

Animals↗
PubMed1987

Assessment of visual impairment in patients with Alzheimer's disease.

We examined five patients with Alzheimer's disease who complained of poor vision. Two patients had mild Alzheimer's disease; they complained of problems with reading and of "bumping into things," yet both had normal visual acuities. One patient with moderate Alzheimer's disease had abnormal eye movements, visual-evoked potentials, and contrast sensitivity. The other two patients had severe Alzheimer's disease. Despite difficulties in performing the examination, we were able to see moderate impairments in visual acuity and visual fields, as well as marked dyschromatopsia, severe deficits in contrast sensitivity, and markedly abnormal eye movements and visual-evoked potentials.

Aged↗
PubMed1987

Monoclonal antibody identification of subpopulations of cerebral cortical neurons affected in Alzheimer disease.

Neuronal degeneration is one of the hallmarks of Alzheimer disease (AD). Given the paucity of molecular markers available for the identification of neuronal subtypes, the specificity of neuronal loss within the cerebral cortex has been difficult to evaluate. With a panel of four monoclonal antibodies (mAbs) applied to central nervous system tissues from AD patients, we have immunocytochemically identified a population of vulnerable cortical neurons; a subpopulation of pyramidal neurons is recognized by mABs 3F12 and 44.1 in the hippocampus and neocortex, and clusters of multipolar neurons in the entorhinal cortex reactive with mAb 44.1 show selective degeneration. Closely adjacent stellate-like neurons in these regions, identified by mAB 6A2, show striking preservation in AD. The neurons recognized by mAbs 3F12 and 44.1, to the best of our knowledge, do not comprise a single known neurotransmitter system. mAb 3A4 identifies a phosphorylated antigen that is undetectable in normal brain but accumulates early in the course of AD in somas of vulnerable neurons. Antigen 3A4 is distinct from material reactive with thioflavin S or antibody generated against paired helical filaments. Initially, antigen 3A4 is localized to neurons in the entorhinal cortex and subiculum, later in the association neocortex, and, ultimately in cases of long duration, in primary sensory cortical regions. mAb 3F12 recognizes multiple bands on immunoblots of homogenates of normal and AD cortical tissues, whereas mAb 3A4 does not bind to immunoblots containing neurofilament proteins or brain homogenates from AD patients. Ultrastructurally, antigen 3A4 is localized to paired helical filaments. Using these mAbs, further molecular characterization of the affected cortical neurons is now possible.

Alzheimer Disease↗
PubMed1986

Optic-nerve degeneration in Alzheimer's disease.

Alzheimer's disease is a dementing disorder of unknown cause in which there is degeneration of neuronal subpopulations in the central nervous system. In postmortem studies, we found widespread axonal degeneration in the optic nerves of 8 of 10 patients with Alzheimer's disease. The retinas of four of the patients were also examined histologically, and three had a reduction in the number of ganglion cells and in the thickness of the nerve-fiber layer. There was no retinal neurofibrillary degeneration or amyloid angiopathy, which are typically seen in the brains of patients with Alzheimer's disease. The changes we observed in the patients with Alzheimer's disease were clearly distinguishable from the findings in 10 age-matched controls and represent a sensory-system degeneration that occurs in Alzheimer's disease. Study of the retina in patients with this disease may be helpful diagnostically, and isolation of the affected ganglion cells may facilitate molecular analysis of the disorder.

Aged↗
PubMed1984

Primary rhabdomyosarcoma of the cerebellum--a light, electron microscopic, and immunohistochemical study.

A primary cerebellar rhabdomyosarcoma (RMS) in a six and a half year old boy is reported. Microscopy of the surgical material revealed lobules of closely packed cells with a high mitotic rate, pleomorphic hyperchromatic nuclei and scant cytoplasm. At their periphery, the lobules merged with rounded cells with similar nuclei but more abundant cytoplasm. These areas were surrounded by interlacing fascicles of strap cells, which were occasionally multinucleated and showed cross striations. Electron microscopy (EM) revealed the primitive nature of the closely packed cells; however, occasional intermediate size filaments were present within their cytoplasm and focal basement membrane accumulation was observed. Cells with more abundant cytoplasm had large accumulations of thick and thin filaments while strap cells showed well-developed cross striations. Immunohistochemical studies (peroxidase-antiperoxidase technique) showed vimentin in the primitive cells and desmin, myoglobin and adenosine triphosphatase as the tumor cells appeared more differentiated. Immunoreaction with antibodies against glial fibrillary acidic protein, S-100 protein and neurofilament protein were negative. Electron microscopic and immunohistochemical studies in this case demonstrated that this was an exclusively mesenchymal tumor with rhabdomyoblastic differentiation and that the pattern of differentiation follows that seen in normal myogenesis.

Cerebellar Neoplasms↗
PubMed1984

Lambdoid synostosis. Part 1. The lambdoid suture: normal development and pathology of "synostosis".

The microscopic development of the normal lambdoid suture was studied in autopsy specimens from 19 normal subjects ranging in age from 20 weeks' gestation to 60 years. The cellular activity at the suture varied considerably with age; however, maximal activity was seen in specimens approximately 3 months of age. There were several unusual features, including a high incidence of cartilaginous differentiation and the presence of intrasutural Wormian bones. Forty-one specimens from 37 patients with isolated lambdoid synostosis were also studied pathologically. Only three cases showed bone union across the suture, which appears to be a result of closure rather than fusion as in other synostoses. The remainder of the cases showed varying degrees of increased cellular proliferation at the suture line, resulting in exaggerated and prolonged sutural activity. Morphologically, this produced increased interdigitation and fibrous adhesion between the suture margins.

Adolescent↗
PubMed1984

Lambdoid synostosis. Part 2: Review of cases managed at The Hospital for Sick Children, 1972-1982.

Seventy-four patients with premature union of the lambdoid suture were treated at The Hospital for Sick Children during the years 1972 through 1982. Lambdoid synostosis is considered to be a rare form of craniosynostosis, but this is more likely due to lack of recognition rather than to infrequent occurrence. The skull deformity resulting from lambdoid synostosis is often mistakenly attributed to positional molding rather than to actual synostosis. When the lambdoid suture closes, the occiput on the involved side is flat, the forehead on the same side tends to bulge forward, and the ear on this side adopts a low and forward position. Skull x-ray films may demonstrate obliteration of the lambdoid suture, but more frequently one sees sclerosis along one edge of the closing suture. Radionuclide bone scanning will show increased activity during the active phase of union and decreased or absent activity once union has occurred. Craniectomy performed during the neonatal period will correct the deformity and provide for normal cranial growth. Delay in surgery beyond 6 months will frequently necessitate a more extensive cranial repair.

Cranial Sutures↗
PubMedDate not supplied

Retinal pathology in Alzheimer's disease. II. Regional neuron loss and glial changes in GCL.

Detailed analyses of neuronal and astrocyte cell numbers in the ganglion cell layer (GCL) of whole-mounted peripheral retinas from 16 Alzheimer's disease (AD) and 11 control eyes (11 and 9 cases, respectively) demonstrate extensive neuronal loss throughout the entire retina in AD as compared to control eyes. The observed neuronal loss is most pronounced in the superior and inferior quadrants, ranging between 40 and 49% throughout the midperipheral regions, and reaching 50-59% in the far peripheral inferior retina, while the overall neuronal loss throughout the entire retina amounts to 36.4% (p < 0.004). Although the 16% increase in astrocyte numbers is not significant, the ratio of astrocytes to neurons is significantly higher (82%; p < 0.0008) in AD as compared to normal retina (0.238 +/- 0.070 vs. 0.131 +/- 0.042). These results are strengthened by the close agreement (within +/- 15% of respective means) found between fellow eyes. Analysis of glial fibrillary acidic protein immunoreactivity (GFAP-ir) in sections of retinas from an additional 12 AD and 19 control cases show increased GFAP-ir with more extensive labeling of astrocytes in the GCL as well as increased labeling of Müller cell end-feet and radial processes in AD as compared to control retinas. The extensive loss of neurons documented in these retinas, accompanied by an increased astrocyte/neuron ratio, provides further support for the substantial involvement of the retina in AD.

Aged↗
PubMedDate not supplied

Retinal pathology in Alzheimer's disease. I. Ganglion cell loss in foveal/parafoveal retina.

Morphometric analysis of the numbers of neurons in the ganglion cell layer (GCL) of the central retina (fovea/foveola/parafoveal retina) in eyes from 9 Alzheimer's disease (AD) and 11 age-matched control cases revealed an overall decrease of 25% in total numbers of neurons in AD as compared with control eyes. Detailed analyses of GCL neurons at various eccentricities from the foveola showed that the greatest decrease in neuronal density (43% decrease) occurred in the central 0-0.5 mm (foveal region), while at 0.5-1 mm and at 1-1.5 mm eccentricities, neuronal loss amounted to 24 and 26%, respectively. The temporal region of the central retina appeared most severely affected, with up to 52% decrease in neuronal density near the foveola (central 0-0.5 mm eccentricity). There was close agreement between fellow eyes analyzed separately for three AD and three control cases. Analysis of neuronal sizes showed that all sizes of neurons were similarly affected in AD. In the GCL of control retinas, neurons decreased with age (coefficient of correlation = -0.67), while in AD retinas no such relationship was evident. Since in the central 0-2 mm region of the retina 97% of neurons in the GCL are ganglion cells (while the remaining 3% consist of displaced amacrine cells), these results demonstrate extensive ganglion cell loss in the central retina in AD.

Age Distribution↗
PubMedDate not supplied

Mitochondrial DNA deletions are rare in the free radical-rich retinal environment.

We measured the levels of a somatic, 4977 bp deletion of mitochondrial DNA (mtDNA4977) in paired neural retinal and optic nerve tissues from 14 adults and 1 infant using a quantitative PCR assay. MtDNA is prone to free radical damage, and areas in the brain that are exposed to high levels of free radicals are observed to accumulate higher levels of the mtDNA4977 deletion. The levels of mtDNA deletions also increase with age in many tissues. Despite the presence of a free radical rich environment, mtDNA from the neural retina possessed extremely low mtDNA4977 levels (0.0001-0.001%). Deletion levels were always lower than those in the optic nerve from the same eye and do not appear to increase with age. Our results suggest that antioxidant defenses in the neural retina are effective in protecting mtDNA against oxidative damage.

Adolescent↗
PubMedDate not supplied

Interferon beta affects retinal pigment epithelial cell proliferation via protein kinase C pathways.

BACKGROUND: The aim of this study is to see the effect of interferon beta (IFN-beta) on cell proliferation and the protein kinase C (PKC) signaling pathway. METHODS: Proliferation of cultured human retinal pigment epithelium (RPE) cells, with various concentrations of IFN-beta, and with or without 3% fetal calf serum (FCS), was assessed by cell counting. Effects of short (3 h) or prolonged (48 h) exposure of RPE cells to natural human IFN-beta were assessed by (3)H-thymidine uptake. Cytosolic and membranous PKC activity over time in cells treated with IFN-beta and calphostin C was also measured. RESULTS: IFN-beta inhibited the increased proliferation by FCS in the prolonged-exposure assay. The PKC inhibitor calphostin C also showed an inhibitory effect on RPE cell growth and (3)H-thymidine uptake in the chronic exposure with FCS. Short treatment with IFN-beta had no inhibitory or stimulatory effect on (3)H-thymidine uptake. Cytosolic and membranous PKC activity was strongly upregulated after short IFN-beta exposure but returned to original levels after 1 h. PKC activity was downregulated both in the cytosol and membrane after 24 or 48 h. CONCLUSION: IFN-beta inhibited RPE proliferation in vitro and the effect is mediated by upregulation of the PKC pathway.

Cell Division↗
PubMedDate not supplied

Cytologic features of secretory meningioma.

OBJECTIVE: To describe the cytologic features of secretory meningioma on crush preparations. STUDY DESIGN: In five cases, the diagnosis of secretory meningioma was made and crush preparations were available. In each case, crush preparations were made at the time of intraoperative consultation from an open biopsy specimen or stereotactic biopsy. RESULTS: Hematoxylin and eosin-stained crushes showed the presence of clusters of cohesive cells containing variable numbers of inclusions among less cohesive typical meningothelial cells. In two cases, the inclusions were especially prominent. Inclusions varied in size from 3 to 40 microns, had a well-defined rim and contained finely granular or hyaline material and a central core. CONCLUSION: Secretory meningiomas demonstrate distinct cytologic features on crush preparations. Recognition of these inclusions is important since their prominence in some stereotactic smear preparations may lead to diagnostic problems.

Aged↗
PubMedDate not supplied

Cytologic features of hemangioblastoma: comparison with meningioma, anaplastic astrocytoma and renal cell carcinoma.

OBJECTIVE: To compare the features of intraoperative smears of hemangioblastomas with those of tumors with which it is most likely to be confused: meningiomas, anaplastic astrocytomas and renal cell carcinomas. STUDY DESIGN: Examples of hemangioblastomas with high-quality intraoperative smears were retrieved from the files of University Hospital, University of Southern California and Los Angeles County-University of Southern California. The characteristics of these smears were compared to those of meningiomas, anaplastic astrocytomas and renal cell carcinomas by two observes. RESULTS: Smears of hemangioblastomas were cellular but remarkably cohesive. Cytoplasmic borders were indistinct. The nuclei were hyperchromatic and mildly pleomorphic and had a relatively evenly dispersed chromatin pattern. Hemosiderin was invariably present. Smears of meningiomas, anaplastic astrocytomas and renal cell carcinomas were more discohesive than those of hemangioblastomas. Smears of hemangioblastomas lacked the cytoplasmic fibrillarity of those of astrocytic neoplasms and distinct cytoplasmic borders seen in smears of renal cell carcinoma. The nuclear features of the four neoplasms studied also differed. CONCLUSION: Smears of hemangioblastomas have characteristic features that differ reliably from those of meningiomas, anaplastic astrocytoma and renal cell carcinoma, neoplasms that commonly enter the differential with hemangioblastoma. Thus, a cytologic smear preparation made at the time of frozen section may be an invaluable aid in the intraoperative diagnosis of hemangioblastoma.

Adult↗