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Biomedical subjects

M Berry

Publications and source records attributed to M Berry.

At least 145 records · Page 8Linked to original sources

Meningeal cells organize the superficial glia limitans of the cerebellum and produce components of both the interstitial matrix and the basement membrane.

We have investigated the factors controlling both the morphological transformation of glial processes into endfeet and the deposition of extracellular matrix molecules into the overlying basement membrane by destroying meningeal cells over the hamster cerebellum by 6-hydroxydopamine administration on the day of birth. We report that within 24 h of destruction of meningeal cells, the concentrations of fibrillary collagens types I, III and IV in the glia limitans externa and the associated basement membrane molecules laminin, collagen type IV, and fibronectin are greatly diminished, resulting in the development of focal gaps in the basement membrane. The immunohistochemical integrity of the basement membrane is restored within 3 days over those surfaces of the folial apices where meningeal cells reappear. Likewise, the fibrillary collagens of the associated interstitial matrix are re-established in the same amounts as in controls. However, meningeal cells remain permanently absent from fissures and all extracellular matrix molecules tested disappear from rostral cerebellar folia covered by the anterior medullary velum. Moreover, the glial endfeet make up the superficial glia limitans only on folial apices, while they disappear from the fissural surfaces. In primary cultures, meningeal cells produce the fibrillary collagens type I, III, and VI, and the matrix molecules fibronectin and laminin, collagen type IV, nidogen, and heparansulphate proteoglycan. These findings indicate that meningeal cells (i) produce molecular components of both the interstitial matrix and the basement membrane, and (ii) are involved in the morphological transformation of glial fibres into the endfeet which constitute the superficial glia limitans.

Animals↗

Three-dimensional morphology of astrocytes and oligodendrocytes in the intact mouse optic nerve.

The three-dimensional morphology of astrocytes and oligodendrocytes was analysed in the isolated intact mature mouse optic nerve, by correlating laser scanning confocal microscopy and camera lucida drawings of single cells, dye-filled with lysinated rhodamine dextran or horseradish peroxidase, respectively. These techniques enabled the entire process field of single dye-filled cells to be visualized in all planes and resolved the fine details of glial morphology. Morphometric analysis showed that the processes of all astrocytes had branches ending at the pial surface, on blood vessels, and freely in the nerve; branches ending in the nerve were described to end at nodes of Ranvier in the accompanying paper. Astrocytes were classified into a single morphological population in which each cell subserved multiple functions. The results of this study do not support the contention that astrocytes can be subdivided into two morphological and functional subtypes, namely type-1 and type-2, which have process ending either at the glia limitans or at nodes, respectively. Three-dimensional analysis of oligodendrocyte units, defined as the oligodendrocyte, its processes and the axons it ensheaths, showed the provision of single myelin segments for an average of 19 nearby axons (range 12-35) with a mean internodal length of 138 microns (range 50-350 microns). Mouse optic nerve oligodendrocytes were a homogeneous population and were markedly similar to those in the rat optic nerve. The results of our analysis of oligodendrocyte morphology are consistent with the view that the number and internodal length of myelin sheaths supported by a single oligodendrocyte are related to the diameter of the ensheathed axons.

Animals↗

Astrocyte associations with nodes of Ranvier: ultrastructural analysis of HRP-filled astrocytes in the mouse optic nerve.

Astrocytes are implicated in the function of nodes of Ranvier because their perinodal processes form contacts with the axonal membrane at nodes. We have filled astrocytes iontophoretically with horseradish peroxidase in the intact mouse optic nerve to resolve the precise relationship between perinodal processes and astrocyte three dimensional structure. We confirm that nodal contacts were formed either by single processes which almost completely enveloped nodes, or by delicate, finger-like projections from larger processes which made discrete nodal contacts. A single perinodal process can form multiple contacts with a node and nodes were contacted by processes from more than one astrocyte. Perinodal processes emanated from larger processes, which terminated as end-feet on blood vessels and at the pia, as well as collateral branches which subsequently ended at nodes; these latter may specifically subserve nodes. Perinodal contacts were also formed directly by the soma and cytoplasmic expansions of the cell body. Both primary processes and collateral branches formed multiple associations with nodes which often appeared in clusters. Thus, all astrocytes formed multiple contacts with nodes, blood vessels and the subpial glia limitans. We conclude that perinodal processes are not formed by a specialized astrocyte in the mouse optic nerve.

Animals↗

Congenital absence of both fibulae in four siblings.

Fibular agenesis/hypoplasia is the most common reduction malformation affecting the long bones. Agenesis of both the fibulae, however, is rare, and its occurrence in four consecutive pregnancies has not been reported so far. We report our experience with one such case.

Adult↗

Growth factors in CNS repair and regeneration.

Traumatic central nervous system (CNS) injury is a significant clinical problem in the developed world. After injuries that penetrate into either the mature brain or spinal cord, damaged neurons initially begin to regrow, but this regeneration is aborted as a fibrotic scar is laid down within the wound. Reconnection of several neuronal pathways does not occur. Functional recovery from such injuries is therefore poor and morbidity severe, particularly for those patients with spinal cord damage. Although palliative measures are available to improve the quality of life, there is no accepted treatment to restore impaired sensory or motor function, so patients remain significantly and permanently debilitated. However, the rapid recent advances that have been made in our understanding of the underlying cellular and trophic pathology of such injuries offer the potential for development of novel therapies to control scarring, enhance neuron survival and stimulate axon regeneration, thereby promoting functional recovery.

Animals↗

Energy metabolism in free-living, 'large-eating' and 'small-eating' women: studies using 2H2(18)O.

The doubly-labelled water (2H2(18)O) technique was used to assess the long-term rates of energy expenditure and, after accounting for any changes in body composition, the derived rates of energy intake in weight-stable 'large-eating' (n 6) and 'small-eating' (n 6) women. The self-reported energy intakes (approximately 11.2 v. 5.6 MJ/d) and energy expenditures (approximately 8.5 v. 12.4 MJ/d) for the 'large-eating' and 'small-eating' groups respectively, should not be sustainable without significant body-weight changes. 2H2(18)O-assessed rates of energy expenditure for the 'large-eaters' (approximately 8.5 MJ/d) and 'small-eaters' (approximately 11.3 MJ/d) were in close agreement with the results obtained using 5 d, self-reported activity diaries but the derived rates of energy intake for the 'large-' (approximately 8.5 MJ/d) and 'small-eaters' (approximately 10.8 MJ/d) were markedly different from those obtained using self-reported, weighed food diaries. When two 'small-eaters' were supplied with their self-reported energy intakes (approximately 5 MJ/d) for up to 28 d both subjects lost about 0.75 kg body-weight/week. These results provide no support for the existence of 'metabolically efficient' women in the community.

Adult↗

Ironic catastrophes: one's food--another's poison.

Iron deficiency is an important nutritional problem in third world countries because it diminishes work performance. In meat-eating countries, iron excess may be more important than iron deficiency. Heme iron is more efficiently absorbed from the diet than inorganic iron, and iron excess can produce cellular oxidation in association with superoxide dismutase. Metal ion catalysis is linked to aging, coronary artery disease, stroke, carcinogenesis, neurodegenerative disorders, and inflammatory disorders. Prudence is advised in the excessive consumption of meat and iron supplementation of the diet until this process is more thoroughly investigated.

Diet↗

Cushing's disease: pituitary imaging.

Fourteen patients with adrenocorticotropic hormone (ACTH)-dependent hypercortisolism underwent pituitary scanning with computed axial tomography (CT) and magnetic resonance imaging (MRI). Computed tomography revealed pituitary macroadenomas in two patients, pituitary hyperplasia in one and a suspicion of pituitary microadenoma in one. Thirteen patients underwent MRI. One with a macroadenoma diagnosed on CT did not undergo MRI. The MRI revealed a pituitary macroadenoma in one, microadenoma in three and hyperplasia in two cases. Magnetic resonance imaging following gadolinium diethylene triamine penta acetic acid (gd-DTPA) enhancement revealed four more pituitary microadenomas. All patients who had pituitary adenomas (micro and macro) and hyperplasia underwent trans-sphenoidal pituitary surgery. One of the two patients, who had an enlarged pituitary on imaging but no demonstrable adenoma, was found to have a microadenoma at surgery. Patients with ACTH-dependent hypercortisolism should undergo MRI of the pituitary gland to identify/localize corticotroph pituitary adenomas. The study should include gd-DTPA enhancement in cases where the scan is normal.

Adenoma↗

Fibroblast growth factor in the hypothalamic-pituitary axis: differential expression of fibroblast growth factor-2 and a high affinity receptor.

In situ hybridization and immunohistochemistry were used to map gene expression and protein distribution of basic fibroblast growth factor (FGF-2) in the hypothalamic-pituitary system. Although the expression of FGF-2 mRNA in the pituitary is low, the protein is widely distributed in both its neural and anterior lobes. In the anterior lobe, immunoreactive (ir-) FGF-2 localizes to basement membranes and select endocrine cells. In the neural lobe, ir-FGF-2 is detected in basement membranes, pituicytes, and Herring bodies. Analyses of FGF high affinity receptor (FGFR) immunoreactivity in the anterior pituitary establishes a distribution of FGFR similar to that of FGF-2. In the neural lobe, ir-FGFR is associated with nerve fibers, pituicytes, and Herring bodies. Unlike FGF-2, the distribution of FGFR1 mRNA correlates well with the presence of the immunoreactive receptor. In the hypothalamus, magnocellular neurons of paraventricular and supraoptic nuclei contain ir-FGF-2 and ir-FGFR. In the median eminence, ir-FGF-2 and ir-FGFR is associated with fibers, glial, and endothelial cells. Ependymal and subependymal cells lining the third ventricle also show high levels of ir-FGF-2 and ir-FGFR and mRNAs. Overall, there is a specific and selective distribution of FGF-2 and its high affinity receptor(s) in the hypothalamo-pituitary axis. This localization lead us to postulate a role in neurohypophyseal functions, possibly water balance.

Animals↗

Coordinated pattern of expression and localization of insulin-like growth factor-II (IGF-II) and IGF-binding protein-2 in the adult rat brain.

Insulin-like growth factors (IGFs) have numerous actions on neuronal and glial cell function in vitro, although their in vivo roles within the central nervous system (CNS) remain undefined. Levels of IGF-II are high in most rat tissues before the third postnatal week, but rapidly decrease thereafter, except in the brain and spinal cord, where elevated titers are present in the adult. This suggests a function of IGF-II within the CNS. IGF-binding proteins (IGFBPs) modify the type 1 IGF receptor-mediated activity of IGFs, thereby regulating the activities of IGF-II in the CNS. In this study, we use a ribonuclease protection assay, in situ hybridization, and immunohistochemistry to demonstrate that IGF-II and one of the major CNS binding proteins, IGFBP-2, show a striking congruency in their anatomical pattern of expression and localization throughout the adult rat brain. Both proteins are synthesized predominantly in the leptomeninges, choroid plexus, and parenchymal microvasculature, but become localized, remote from the site of synthesis, in the myelin sheaths of individual myelinated axons and in all of the myelinated nerve tracts in the brain, which presumably represents the site of IGF-II bioactivity. The spatial disparity between sites of synthesis and sites of bioactivity suggests a key role for IGFBP-2 in the regulation of IGF-II bioavailability within the brain.

Animals↗

Lymphocytic hypophysitis. Case report.

A case of lymphocytic hypophysitis is described in a patient presenting with panhypopituitarism 8 years after her last childbirth. The patient developed headache, vomiting, and diplopia (due to palsy of the right lateral rectus muscle) 7 months after delivery of her last baby. The diplopia disappeared after a few days with symptomatic treatment, and the headache and vomiting decreased in intensity with analgesic therapy. Eight years later the patient developed symptoms suggestive of hypoadrenalism, hypothyroidism, and amenorrhea. Investigations revealed panhypopituitarism with a pituitary mass lesion. Repeat evaluation 1 year later demonstrated no change in the size of the pituitary gland. The patient underwent transsphenoidal surgery with a provisional diagnosis of pituitary adenoma. Histological examination of the resected gland revealed evidence of lymphocytic hypophysitis. Symptoms suggestive of a pituitary mass lesion were noted during the peripartum period, but features of hypopituitarism developed much later. Such a long latent period has not been reported before. This report also highlights the fact that glandular enlargement may persist for many years after the onset of lymphocytic hypophysitis.

Adult↗

Embryonic optic nerve tissue fails to support neurite outgrowth by central and peripheral neurons in vitro.

The failure of axon regeneration in the injured mammalian central nervous system has been ascribed, in part, to the inhibitory effects of myelin proteins. To investigate the influence of myelination on neurite growth and regeneration by both central nervous system and peripheral nervous system neurons, isolated rat neonatal retinal ganglion cells and adult and neonatal dorsal root ganglion neurons were cultured on cryostat sections of both immature unmyelinated and mature fully myelinated adult rat optic nerve. In agreement with earlier studies using neonatal peripheral neurons, the adult optic nerve failed to support neurite outgrowth from any of the neurons tested. A new finding was that tissue sections from unmyelinated optic nerve (aged embryonic days 18 and 20, and postnatal days 1-3), also failed to support the growth of neurites from neonatal retinal ganglion cells and both neonatal and adult dorsal root ganglion neurons. Neonatal retinal ganglion cells also failed to extend neurites on sections of pre-degenerated sciatic nerve, a tissue shown in our previous work to be a good substratum for supporting neurite growth for both neonatal and adult DRG neurons. These results suggest that cells in the immature optic nerve either express widely acting axon growth inhibitory molecules unrelated to previously described myelin proteins, or do not synthesize appropriate axon growth promoting molecules. They also reveal that, for axon regeneration, central nervous system and peripheral sensory neurons require distinct substratum interactions.

Aging↗

The regulation of human globin gene switching.

This paper describes the mechanism of regulation of the human beta-globin on the basis of a number of natural mutations and experiments in transgenic mice. From these data we conclude that this multigene locus is regulated at a number of different levels involving specific interactions between the Locus Control Region (LCR) and the individual genes. Most important is the action of stage specific transcription factors acting on sequences immediately flanking the genes. In addition, specificity is obtained through specific interaction of the genes with the LCR and through competition of the genes for interaction with the LCR.

Animals↗