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Biomedical subjects

D M Landis

Publications and source records attributed to D M Landis.

At least 55 records · Page 3Linked to original sources
PubMed1985

Ultrastructural study of cholecystokinin-immunoreactive cells and processes in area CA1 of the rat hippocampus.

We used light and electron microscopic immunocytochemical methods to examine the structure of neuronal perikarya and processes containing cholecystokinin-like immunoreactivity (CCK-IR) in area CA1 of the rat hippocampus. The morphology of stained perikarya, their positions within all laminae, and the orientation of their dendrites indicate that CCK-IR is located in interneurons. These cells were seen in the electron microscope to have deeply folded nuclei and to receive both symmetric and asymmetric synaptic junctions on their cell somata and dendritic shafts. Their dendrites are essentially spine-free, but form bulges at the site of some asymmetric synaptic junctions. Axonal varicosities containing CCK-IR make symmetric synaptic junctions with cell somata and dendritic shafts of both pyramidal and non-pyramidal neurons. In addition, CCK-IR varicosities form symmetric junctions with unstained non-pyramidal neurons and with CCK-IR cells, suggesting either recurrent innervation of one cell on itself or interaction between interneurons. The presence of CCK-IR varicosities and synaptic junctions on pyramidal cells is in agreement with physiological data which indicate that CCK has a direct postsynaptic action. The observation of CCK-IR varicosities forming synaptic junctions on non-pyramidal cells suggests that CCK might also modify the response of interneurons.

Animals↗
PubMed1985

Organization of the cerebellar cortex viewed by scanning electron microscopy.

An improved method of preparing central nervous system tissue for examination in a scanning electron microscope is described. In cerebellar cortex, the precise distribution of synaptic junctions on Purkinje cell bodies, as well as complex arrangements of neurites in the glomeruli of the granule cell layer, are directly visualized. The method also provides views of glial cell processes investing brain surfaces, blood vessels and neurons. The principal advantage of a scanning electron microscopic study is that relationships between cells in the brain can be seen directly instead of inferred from laborious serial reconstructions or other more complex and indirect anatomical methods.

Animals↗
PubMed1984

Communicating hydrocephalus and lysosomal inclusions in mannosidosis.

A 32-year-old man with mannosidosis had a gait disorder develop that was associated with communicating hydrocephalus. The gait disorder improved with ventriculoperitoneal shunting, but proximal muscle weakness remained. Biopsy specimens of muscle and nerve disclosed typical lysosomal inclusions in both tissues, as well as selective loss of unmyelinated axons.

Adult↗
PubMed1984

Implications of neuropeptides in neurological diseases.

Neuropeptides are sufficiently stable to allow valid radioimmunoassay of peptide concentrations in post-mortem human nervous tissue and in human cerebrospinal fluid. Studies have now documented abnormalities of peptide concentrations in degenerative diseases of the brain. Somatostatin concentration is reduced in the hippocampus and neocortex of patients dying with Alzheimer's type dementia. In Huntington's disease, there are reduced concentrations of substance P, met-enkephalin and cholecystokinin in the basal ganglia; in contrast the concentrations of somatostatin and TRH are increased. Immunocytochemical and experimental lesion studies are underway in an attempt to localize the peptide-containing cells affected by these disorders; and the potential role of alterations in neuropeptide function in the pathogenesis, clinical manifestations and therapy of these illnesses is of great interest. Although alterations of CSF peptide concentrations have been reported in a variety of human diseases, interpretation of these results requires knowledge of the origin and disposition of CSF peptides. Future research into the pathology of peptidergic systems will depend on the development of specific peptide antagonists to probe dynamic aspects of peptide function and on the application of the tools of molecular biology, such as specific mRNA assays, to human material.

Alzheimer Disease↗
PubMed1984

Cysteamine depletes prolactin (PRL) but does not alter the structure of PRL-containing granules in the anterior pituitary.

Cysteamine causes a profound depletion of PRL in the anterior pituitary and in the systemic circulation, as measured by RIA and bioassay. However, electron microscopic study of PRL-containing cells in rat anterior pituitary does not reveal changes in secretory granule or cytoplasmic structure during the interval of depressed PRL content and of subsequent recovery to normal levels. In contrast to the results obtained by RIA, PRL-like immunoreactivity as detected by immunocyto-chemistry is present and similar to that of control preparations after cysteamine administration. We suggest that cysteamine alters PRL structure in secretory granules, probably by interacting with the disulfide bonds of PRL, thereby altering bioactivity and immunoreactivity. The presence of cysteamine-altered PRL in secretory granules does not seem to trigger degradation of granules by the lysosomal system.

Animals↗
PubMed1983

Immunocytochemical studies of substance P and leucine-enkephalin in Huntington's disease.

The distribution of substance P and leucine-enkephalin in selected regions of brain obtained postmortem from patients with Huntington's disease and from neurologically normal persons has been studied with immunocytochemical techniques. In the normal brain, substance P immunoreactivity was identified in medium-sized neurons in the neostriatum, in neurons of the external segment of the globus pallidus, and in fine fibers in teh neostriatum, inner segment of the globus pallidus, and in the pars reticulata of the substantia nigra. Huntington's disease brains all exhibited a marked decrease in substance P fiber density in the substantia nigra and globus pallidus. A few medium-sized neurons with substance P immunoreactivity remained in the neostriatal remnant. Leucine-enkephalin immunoreactive processes were present throughout the neostriatum of normal brain, and were densely packed in the external segment of the globus pallidus and in the substantia nigra. A uniform population of medium-sized neurons containing immunoreactive leucine-enkephalin was present in the caudate and putamen. By contrast, in the Huntington's disease brains there was a marked diminution of fiber staining in the globus pallidus and substantia nigra. A few medium-size neurons and sparse fibers with leucine-enkephalin immunoreactivity persisted in the atrophic neostriatum. These observations are consistent with previous reports of regional peptide concentrations in both normal and Huntington's disease brain. Cells containing substance P and leucine-enkephalin immunoreactivity persist in the basal ganglia in brains from patients with Huntington's disease, and we have no evidence that cellular content of one or the other peptide is associated with disproportionate cell death or survival.

Adolescent↗
PubMed1983

Membrane structure in cultured astrocytes.

Astrocytes cultured from the brains of neonatal rat pups acquire at least two specializations of intramembrane particle distribution: 'assemblies' and gap junctions. The number and appearance of assemblies in the cultured astrocytes is not markedly influenced by the presence or absence of a collagen substrate, and the range of concentrations of assemblies in astrocytic membranes is fairly stable from 7 through 28 days in culture. The assemblies are not concentrated in apposition to the substrate, even though the astrocytic membranes containing the highest concentration of assemblies in vivo are apposed to basal lamina. Quantitative analysis shows that assemblies are not uniformly distributed over the plasmalemma of a single cell, raising the possibility that the nature of cells around an astrocytic process may influence its membrane composition in vitro.

Animals↗
PubMed1983

Development of synaptic junctions in cerebellar glomeruli.

In the glomerular synapses of developing mouse cerebellar cortex, 2 components of the synaptic junctions assemble independently in the immature granule cell dendrites, and then combine. 'Initial' junctions between mossy fiber axons and immature granule cell dendrites have presynaptic and postsynaptic electron-dense fuzz and a widened synaptic cleft, but lack the aggregate of intramembrane particles associated with the extracellular half of the postsynaptic membrane which characterizes mature synaptic junctions. In the vicinity of 'initial junctions' there are particle aggregates which resemble those at mature synaptic junctions, but which are less densely packed and which are not associated with the other features of a junction. The constituent particles of these aggregates move to the sites of 'initial junctions' to combine with them and form 'immature synaptic junctions'. Many of these immature junctions are larger in area than mature synaptic junctions. The immature junctions accumulate a fairly uniform complement of intramembrane particles, which increase in packing density as the junctions decrease in area and attain smaller, adult size.

Animals↗
PubMed1983

Cytoplasmic organization in cerebellar dendritic spines.

Three sets of filamentous structures were found to be associated with synaptic junctions in slices of cerebellar tissue prepared by rapid-freezing and freeze-etch techniques. The electron-dense fuzz subjacent to postsynaptic membranes corresponds to a web of 4-6-nm-diam filaments that were clearly visualized in rapid-frozen, freeze-etched preparations. Purkinje cell dendritic spines are filled with a meshwork of 5-7-nm filaments that were found to contact the spine membrane everywhere except at the synaptic junction, and extend through the neck of the spine into the parent dendrite. In addition, 8-10-nm microfilaments, possibly actin, were seen to be associated with the postsynaptic web and to extend into the body and neck of the spine. The arrangements and attachments of the filamentous elements in the Purkinje cell dendritic spine may account for its shape.

Animals↗
PubMed1982

Cysteamine: a potent and specific depletor of pituitary prolactin.

Cysteamine rapidly reduces the concentration of prolactin in pituitary tissue in vivo and in vitro. The effect is dose-dependent, reversible, and cannot be accounted for by prolactin release. Cysteamine does not appear to exert its effect through dopamine receptors and does not alter lactotrope morphology, as determined by electron microscopy.

Animals↗
PubMed1982

Somatostatin-like immunoreactive material in the rabbit retina.

Somatostatin-like immunoreactivity was detected by a specific radioimmunoassay in extracts of retinas of Dutch-belted rabbits at a mean concentration of 1.1 +/- 0.1 ng/retina, or 170 +/- 30 pg/mg protein. On both gel permeation chromatography and reversed phase high performance liquid chromatography, the majority of this material was indistinguishable from somatostatin-14; a smaller amount of immunoreactive material co-chromatographed with somatostatin-28. The somatostatin-like immunoreactivity was concentrated in a P2 (synaptosomal) fraction prepared by differential centrifugation. The concentration of somatostatin-like immunoreactivity was unaffected by the prior intravitreal injection of the selective neurotoxins 6-hydroxydopamine and 5, 7-dihydroxytryptamine. The rabbit retina, therefore, contains readily detectable amounts of material chemically similar to somatostatin-14 and somatostatin-28. This material is concentrated in neurosecretory elements of the retina, but is not contained in cells which accumulate dopamine or indoleamines. The rabbit retina is suitable for in vitro studies of the central nervous system function of the somatostatin family of peptides.

5,7-Dihydroxytryptamine↗
PubMed1982

Regional organization of astrocytic membranes in cerebellar cortex.

The internal organization of plasmalemmal membrane, as revealed by freeze-fracture techniques, varies dramatically and predictably over the surface of astrocytes in mouse cerebellar cortex. Assemblies of uniform, small intramembrane particles packed in orthogonal order into square or rectangular aggregates are specialized distribution of intramembrane particles which, in the cerebellar cortex, are found only in astrocytes. The concentration of assemblies is greatest in astrocytic membrane juxtaposed to vascular structures or facing the cerebrospinal fluid at the glial limitans. Many fewer are present in regions of astrocytic membrane apposed to neural structures and virtually none are present on the astrocyte cell body. Corresponding structures have not yet been found in thin-sectioned preparations. While the distribution of assemblies in membranes facing blood and cerebrospinal fluid compartments suggests that they may have a role in transport of some material into or out of those compartments, their function is unknown. A second, distinct specialization of intramembrane structure appears to represent a junction between apposed astrocytic processes. We have provisionally described this as a 'polygonal particle junction', since it appears as large, irregular particles densely packed without obvious order in co-extensive regions of two astrocytic membranes. This junction is regularly present just below the cerebellar surface in the processes of the glial limitans as well as between large, more proximal radial Bergmann fibers, and also occurs occasionally throughout the molecular layer. With tannic acid mordant after aldehyde-osmium fixation or rapid freezing and freeze-substitution, it is possible to demonstrate subtle electron-dense specializations of the astrocytic membranes and extracellular matrix in thin-sections which correspond to the sites of polygonal particle junctions. The function of this astrocytic specialization is also unknown. Cerebellar astrocytes manifest numerous gap junctions as well, whose structure in freeze-fractured and thin-sectioned preparations is quite distinct from that of assemblies or of polygonal particle junctions.

Animals↗
PubMed1982

Whipple disease of the nervous system.

A 58-year-old man with dizziness and unsteady gait had a 10-year history of behavioral change, impotence, and a progressive peripheral neuropathy. CT revealed low-density, contrast-enhancing lesions in the right pontine tegmentum and the right medial temporal lobe. Temporal lobe biopsy contained a collection of mature histiocytes, with PAS-positive rod-shaped inclusions. These inclusions, when studied by electronmicroscopy, were seen to be membrane-bound bacilliform bodies. Peroral jejunal biopsy contained no such inclusions. Despite treatment with antibiotics, the patient's neurologic illness progressed, and he succumbed to intercurrent sepsis. We believe this to be the first instance in which a lesion of Whipple disease has been identified within the CNS by CT scan, and the diagnosis made antemortem, in the absence of demonstrable systemic disease.

Biopsy↗
PubMed1981

Astrocyte membrane structure: changes after circulatory arrest.

Membranes of the astrocytic processes investing small blood vessels and the surface of the brain contain numerous arrays of orthogonally packed particles as revealed by the freeze-fracture technique. The structure of these particle arrays, which we have termed "assemblies," is the same whether tissue is prepared for freeze-fracture by conventional fixation or by quick excision and rapid freezing. However, assemblies are progressively replaced by amorphous clumps and then disappear as the interval between decapitation and rapid freezing increases. Nearly normal numbers of assemblies may be maintained in cerebellar slices in vitro, but there too they disappear at low PO2 or in the presence of dinitrophenol. No other neuronal or glial membrane specialization exhibits a comparable lability.

Animals↗
PubMed1981

Golgi and electronmicroscopic studies of spongiform encephalopathy.

Golgi impregnations of cerebral biopsies from two patients suffering from Creutzfeldt-Jakob disease (subacute spongiform encephalopathy) revealed striking loss of dendritic spines of pyramidal neurons and unusual focal spherical distensions of dendritic and axonal processes. Light and electronmicroscopic studies disclosed spongiform changes, which seemed to be caused by intracytoplasmic vacuoles and expansion of the plasmalemmal membranes of neurons and astrocytes. Although the diagnostic biopsies were performed at a markedly symptomatic stage of the disease, there was no evidence of neuronal cell loss. Neuronal changes in Golgi impregnations of cerebral cortex from hamsters infected with scrapie were essentially identical to those in the human biopsies. The loss of dendritic spines of pyramidal cells and spherical swellings of axons and dendrites thus seem to be characteristic of spongiform encephalopathies, and probably account in part for the clinical neurologic manifestations, which may be severe in the relative absence of neuronal death.

Adult↗
PubMed1981

Membrane structure in mammalian astrocytes: a review of freeze-fracture studies on adult, developing, reactive and cultured astrocytes.

The application of freeze-fracture techniques to studies of brain structure has led to the recognition of two unsuspected specializations of membrane structure, each distributed in a specific pattern across the surface of astrocytes. 'Assemblies' (aggregates of uniform, small particles packed in orthogonal array into rectangular or square aggregates) are found to characterize astrocytic plasma membranes apposed to blood vessels or to the cerebrospinal fluid at the surface of the brain. These particle aggregates are much less densely packed in astrocytic processes in brain parenchyma. Assemblies are not fixation artifacts, have been shown to extend to the true outer surface of the membrane, are remarkably labile in the setting of anoxia, and are at least in part protein. The function of assemblies is unknown, but their positioning suggests that they may have a role in the transport of some material into or out of the blood and cerebrospinal fluid compartments. A second specialization of intramembrane particle distribution, the polygonal particle junction, links astrocytic processes at the surface of the brain, and also links proximal, large caliber astrocytic processes in brain parenchyma. The function of this membrane specialization also is unknown, but it may subserve a mechanical role.

Aging↗