Biomedical subjects
Publications and source records attributed to C H Rhodes.
An interesting case of benign nasal polyposis with intracranial extension and subsequent abscess formation is described. Its diagnosis and treatment are presented and the pathology is demonstrated. The literature related to this rare disease process is discussed in detail.
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We raised an antiserum against the synthetic peptide FKETTRSFSNECLGTTR corresponding to the amino terminus of the enzyme peptidylglycine alpha-amidating monooxygenase (PAM). Control experiments were performed to determine the specificity of the antiserum and its suitability for the immunohistochemical identification of PAM-containing cells. An immunoaffinity column made with the antibody coupled to Sepharose permitted the isolation of the active enzyme. Peptide-agarose immunoadsorbant removed the antibodies responsible for the characteristic staining patterns in immunohistochemical experiments. As expected from the widespread distribution of amidated peptides in the nervous system, PAM immunoreactivity was detected in perikarya in a variety of locations, including the pituitary, the hypothalamic periventricular and supraoptic nuclei, neocortex, and sensory ganglia. Punctate immunostained fibers, especially around neuronal perikarya, were observed in regions known to receive amidated peptidergic afferents. In addition, PAM immunoreactivity was observed in some neurons not known to produce amidated peptides (e.g., pyramidal cells of the hippocampus). This result suggests that these neurons also produce an amidated peptide. PAM immunoreactivity was also detected in several unexpected cell types, including ependyma, choroid plexus, oligodendroglia, and Schwann cells. The presence of enzymatically active PAM in Schwann cells was confirmed by measurements of amidating activity in ligated and control sciatic nerve. These results suggest that these non-neuronal cells may produce amidated peptides.
Treatment with neuronal growth factor (NGF) results in the growth of neuronal processes by PC12 cells and a concomitant 70% increase in the area of the Golgi apparatus. To define the observed morphologic changes in biochemical terms, we investigated the effect of NGF treatment on some Golgi and lysosomal enzyme activities of PC12 cells. Enzyme activities characteristic of the Golgi apparatus, lysosomes, plasma membranes, mitochondria, and endoplasmic reticulum were measured in cell homogenates, in post-mitochrondrial supernatants, and in Golgi-enriched fractions from control and from NGF-stimulated PC12 cells. Treatment of PC12 cells with NGF did not change the level of the Golgi activity of UDPGal:GlcNAc galactosyltransferase while that of CMP-sialic acid:lactosylceramide sialyltransferase was increased three- to fivefold in all fractions studied. For lysosomal enzymes, NGF treatment resulted in a two- to threefold higher level of arylsulfatase activity compared to either acid phosphatase or acid alpha-mannosidase activities. These results indicate that there is a selective increase of at least one Golgi and one lysosomal activity as a result of NGF stimulation of PC12 cells. Both of these enzymes are involved in glycolipid metabolism. It is possible that the dramatic morphologic changes observed during NGF-induced differentiation of PC12 cells are associated not only with increased synthesis in the Golgi apparatus of plasma membrane components such as gangliosides, but also with increased degradation in lysosomes of other plasma membrane components such as sulfatide.
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A 56-year-old man with chronic lymphocytic leukemia, progressive multifocal leukoencephalopathy, and a dense left homonymous hemianopia had 18F-fluorodeoxyglucose positron emission tomography. Cortical glucose metabolism was decreased in the right cerebral hemisphere and the left cerebellar hemisphere. To our knowledge, this is the first demonstration of cerebral and cerebellar hypometabolism due solely to white matter disease.
Following intraocular injection in adult rats of 125I-labeled wheat germ agglutinin (I-WGA), the ultrastructural distribution of label in the superior colliculus and lateral geniculate was examined by electron microscope autoradiography. Three days after injection, 5.4% of the label in the lateral geniculate was associated with neuronal perikarya, and 3.6% was associated with glial perikarya. The corresponding figures for the superior colliculus were 5.1% and 0.8%. When the data were expressed as number of grains per micron 2 cytoplasm, there was no statistically significant difference between the grain density over neuronal or glial cytoplasm in either the lateral geniculate or the superior colliculus. A statistical analysis of the distance between the silver grains and the cell membranes showed that in both neurons and glia, the observed labeling was the product of internalized I-WGA and not the result of scatter from the neuropil or from label bound to the surface of the cells. These results indicate that much of the WGA released from axons and axon terminals is not confined to a specific "transsynaptic" pathway, but produces a generalized labeling of nearby cells, much like a microinjection of WGA into the region.
Previous work has established that, following endocytosis, wheat germ agglutinin, like a number of other plasma membrane bound ligands, is transported to the Golgi apparatus-complex. Previous studies that provided qualitative information about the intracellular distribution of internalized wheat germ agglutinin used techniques that precluded any quantitative conclusions about the relative magnitude of the labeling of endosomes, lysosomes, and the Golgi apparatus-complex. Using quantitative ultrastructural autoradiography, this study compares the time course and relative magnitude of labeling of various intracellular compartments to the labeling in the Golgi area. Fifteen minutes after intraocular injection, wheat germ agglutinin is confined to the inner surface of the retina and the immediate subsurface neuropil with little labeling of the retinal ganglion cell perikarya. Thirty minutes after injection, the plasma membrane (6.97 +/- 1.17), endosomes (10.27 +/- 3.98), smooth vesicles and tubules (1.94 +/- 1.66), and lysosomes (2.42 +/- 1.21) of the retinal ganglion cells are labeled, while the Golgi apparatus-complex is not labeled (0.29 +/- 0.25). (Figures in parentheses are the calculated relative radioactive source density +/- the standard deviation.) The relative labeling density of the plasma membrane and endosomes decreases somewhat during the next 90 minutes (plasma membrane, 4.76 +/- 0.67; endosomes, 7.23 +/- 2.02), while the labeling density of smooth vesicles and tubules and of lysosomes rises (smooth vesicles and tubules, 5.56 +/- 0.94; lysosomes, 7.76 +/- 1.56). The Golgi apparatus-complex, which is unlabeled at 30 minutes, is weakly labeled at 2 hours (1.26 +/- 0.28). The fact that the lysosomes are already labeled at 30 minutes while the Golgi apparatus-complex is unlabeled at that time indicates that the transport of wheat germ agglutinin to the Golgi apparatus-complex is a relatively late phenomenon, and suggests that the bulk of the wheat germ agglutinin destined for lysosomes does not pass through the Golgi apparatus-complex.
Recent reports of the transsynaptic transfer of wheat germ agglutinin (WGA) in several systems are consistent with the hypothesis that WGA binds to endogenous glycoproteins(s) which undergo transsynaptic transfer. Such molecules might be involved in trophic interactions between neurons. Since these hypothetical glycoproteins must be soluble proteins (it is unlikely that integral membrane proteins are exchanged between neurons) this preliminary study of the soluble, axonally transported glycoconjugates of the visual system was undertaken. Soluble, tritium-labeled macromolecules which accumulated in the rat lateral geniculate nucleus (LGN) and visual cortex after intraocular injections of tritiated fucose were studied by lectin affinity chromatography and polyacrylamide gel electrophoresis (PAGE). After correction for hematogenously or cerebrospinal fluid transported label, 9.6% of the radioactivity in the LGN and 17.9% of the radioactivity in the visual cortex was found in the soluble fraction of a phosphate-buffered saline homogenate. In the LGN, 31.3% of the axonally transported soluble label was bound by concanavalin-A (Con-A) agarose. The corresponding figure in the visual cortex was 25.7%. Most (greater than 90%) of the label which did not bind Con-A was soluble in 10% trichloroacetic acid (TCA). Eighty-eight percent of the label which bound Con-A was precipitated by 10% TCA. On 7.5% polyacrylamide SDS reducing gels, the Con-A bound material from either the LGN or the visual cortex migrated as a single peak near the origin of the gel (apparent molecular weight greater than 300,000 Da).(ABSTRACT TRUNCATED AT 250 WORDS)
We used quantitative autoradiography to localize thyrotropin releasing hormone (TRH) receptors in human brain. Highest concentrations of TRH receptors were localized within the cortical, basal, and lateral nuclei of the amygdala and the molecular layer of the hippocampus. Low levels were found in the cortex, diencephalon, and basal ganglia. The radioligand bound with similar affinity and pharmacology to pituitary gland as to brain. These data suggest that authentic TRH receptors in the hippocampus and amygdala may mediate the putative effects of TRH on the human brain.
Little information is currently available on the localization of noradrenergic systems in the human CNS. We used quantitative autoradiography with [125I] iodopindolol to examine beta-adrenergic receptors in postmortem human brain. The concentration of beta-receptors was highest in all subfields of the hippocampus, followed by cerebellum, and then thalamic nuclei, basal ganglia, midbrain, and cerebral cortex. Low levels were found in white matter and hypothalamus. This distribution differed from the distribution of beta-receptors reported in membrane homogenates of human brain and also from the distribution of beta-receptors in rat brain determined by autoradiography. The similarities and differences between the distribution of beta-receptors in the human and rat brains may have implications regarding the role of norepinephrine in the CNS of these two species.
A quantitative study of the orthograde axonal transport of iodinated wheat germ agglutinin (I-WGA) and I-WGA conjugated to horseradish peroxidase (I-WGA-HRP) demonstrated labeling of both the lateral geniculate nucleus and the visual cortex following intraocular injections. I-WGA was 13 times more efficient than I-WGA-HRP as a marker of the primary projection from the retina to the geniculate and 3 times more efficient than I-WGA-HRP as a marker of the second order projection to the cortex.
1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) causes parkinsonism in humans and other species. We found [3H] MPTP binding sites that were saturable, specific, and of high affinity. In autoradiographic studies, the highest binding densities of [3H] MPTP occurred in the hypothalamus, interpeduncular nucleus, and ependymal lining of the ventricles. High to moderate binding was seen in the dentate gyrus, caudate, putamen, substantia nigra, and cingulate cortex. The distribution of [3H] MPTP binding correlated with the distribution of [3H] pargyline binding to MAO. Human substantia nigra contains more MPTP binding sites than rat substantia nigra, and this may explain the sensitivity of humans to the neurotoxic effects of MPTP.
Thyrotropin-releasing hormone (TRH) exerts many effects upon spinal cord function in animals, and may also play a role in human spinal cord function. We have used the technique of quantitative autoradiography to anatomically localize specific receptors for TRH within human spinal cord. Highest concentrations of TRH receptors were localized within lamina II, the substantia gelatinosa. A moderate density of TRH receptors was found in lamina IX, the motor neurons of the anterior horn. Low levels of TRH receptors were noted throughout the remainder of the gray matter of the human spinal cord, and no TRH receptors were localized within white matter. This anatomic distribution of TRH receptors within the human spinal cord is consistent with the localization of endogenous TRH and the effects of exogenously applied TRH in animal studies. These results suggest that any effects of TRH on human spinal cord function may be mediated by TRH receptors.
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A cell-by-cell analysis of the magnocellular elements in hypothalami of fifty Long-Evans (normal) and Brattleboro (diabetes insipidus) rats was done using the unlabeled antibody enzyme technique (PAP) with primary antisera directed against oxytocin (OXY), vasopressin (ADH), and the neurophysins. The magnocellular neurons of the hypothalamus were found in the supraoptic (SON), paraventricular (PVN), and anterior commissural (ACN) nuclei, a number of accessory nuclei, and as individual cells in the anterior hypothalamic area. SON was divided by the optic tract into the principal part and retrochiasmatic SON. In retrochiasmatic SON a majority of the cells contained vasopressin. Within the principal part of SON oxytocin-producing cells tended to be found rostrally and dorsally, while the vasopressin cells were more common caudally and ventrally. PVN was divided into three subnuclei, the medial, lateral, and posterior subnuclei, on the basis of cellular morphology and peptide content. The magnocellular cells of the medial and lateral PVN were closely packed together and nearly round, while those of posterior PVN were more separated and fusiform in shape with their long axis running in a medio-lateral direction. Medial PVN consisted primarily of oxytocin-producing cells, while lateral PVN was formed by a core of vasopressin-producing cells with a rim of oxytocin cells. Posterior PVN contained largely oxytocin-producing cells. Both ADH and OXY cells were found in the accessory nuclei. In the Long-Evans rat the SON had, on the average, 1443 OXY and 3236 ADH cells; the PVN had 1174 OXY and 976 ADH cells; and the accessory magnocellular groups in the hypothalamus (including the ACN) had 1286 OXY and 552 ADH cells. The Brattleboro strain animal had similar numbers of cells in these nuclei. (The cells which contain ADH in normal animals were identified in the Brattleboro rat as large, neurophysin-negative cells.) Thus, a large fraction of the magnocellular oxytocin- and vasopressin-producing cells in the rat were located outside of the PVN and SON. One accessory cell group in particular, ACN, had 616 OXY cells, or about 50% as many as PVN. In each nucleus the sum of the numbers of OXY and ADH cells was approximately the number of neurophysin cells.
The effect of water deprivation or estrogen treatment on the oxytocin content of rat hypothalamic cells was examined using a quantitative immunohistological technique. Oxytocin-containing cells were visualized using the immunoperoxidase technique of Sternberg and a primary antiserum directed against oxytocin. The optical density of the darkest 3.2 micrometer diameter spot in the cytoplasm of a cell was used as a measure of the oxytocin content of that cell. Water deprivation produced a significant decrease in anti-oxytocin staining in the anterior commissural nucleus of males and females. There was a similar decrease in the paraventricular nucleus of males, but not in the paraventricular nucleus of females or the supraoptic nucleus of either males or females. Estrogen treatment of ovariectomized female rats produced a fall in anti-oxytocin staining in the anterior commissural, but not paraventricular or supraoptic nuclei.