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Biomedical subjects

M Berry

Publications and source records attributed to M Berry.

At least 163 records · Page 9Linked to original sources

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↗

Optic glioma in children: surveillance, resection, or irradiation?

Eighty-seven consecutive children with newly diagnosed optic glioma were managed at University of Toronto hospitals 1958-1990. Overall the 10-year survival, relapse-free survival and freedom from second relapse rates were 84%, 68% and 85%. Twenty-seven patients relapsed or progressed, of whom 40% were free of a second relapse 10 years after the first relapse. Fourteen patients had a second relapse. Thirteen are dead. None survived 5 years after second relapse. Patients with anteriorly located tumors (N = 35), which involved the optic nerve, or chiasm and optic nerves, fared better than those with posteriorly located tumors (N = 52) with spread beyond the chiasm, 10-year survival 95% versus 76%, (p = .02), 10-year relapse-free survival 80% versus 59% (p = .02), respectively. For posterior tumors primary irradiation was more effective than primary subtotal resection for prevention of subsequent relapse, 10-year relapse-free survival 75% versus 41% (p = .02), but salvage therapy was, in part, successful and multivariate analysis of prognostic factors influencing survival for posterior tumors indicated that neither primary resection nor primary irradiation were significant factors. For first relapse, primary irradiation and the presence of neurofibromatosis were the significant favorable factors. Since 1977 and for posterior optic glioma subtotal resection or surveillance were used in 21/29 (72%) patients compared with 4/23 (17%) previously. Ten-year survival rates before and after 1977 were 78% and 67% and 10-year relapse-free survival 64% and 56%, respectively.

Adolescent↗

Transforming growth factor-beta 1 and basic fibroblast growth factor in the injured CNS.

After injuries that penetrate the mature brain or spinal cord, damaged axons initially show a growth response, but later their regeneration is aborted as a dense permanent scar is laid down within the core of the wound. Functional recovery from such injuries is poor and morbidity is severe, particularly for those patients with spinal cord damage. Clinically, no long term therapeutic treatments have been developed that might inhibit scarring and promote neuronal growth. Consequently, the prevalence of patients permanently disabled from head and spinal cord injury is high, estimated at more than 1:1000 of the population of North America (Office of Technology Assessment USA, 1990). Ann Logan and Martin Berry define the mechanisms that underlie the wound healing response in the CNS and discuss the rationale for the development of novel therapeutic strategies.

Animals↗

Computed tomography of vertebral tuberculosis: patterns of bone destruction.

A retrospective analysis was performed of CT scans of 30 consecutive patients with a clinical suspicion or diagnosis of spinal tuberculosis. Four patterns of bone destruction were noted, namely, fragmentary, osteolytic, subperiosteal and well-defined lytic with sclerotic margins. The fragmentary type was most common (47%). Intervertebral disc destruction was always associated with contiguous vertebral body destruction. Associated paravertebral soft-tissue masses were seen in all patients. Epidural extension of disease was seen in 66% and showed a very good correlation with neurological signs on clinical evaluation. Bone fragments were detected in the epidural soft-tissue mass in 65% of patients with epidural extension of disease. CT appearances of bone destruction are highly suggestive of tuberculous osteomyelitis in about half the patients.

Adult↗

No major differences in energy metabolism between matched and unmatched groups of 'large-eating' and 'small-eating' men.

Rates of energy expenditure (J/kg fat-free mass (FFM) per min) in normal weight, 'small-eating' men were compared with those obtained for normal weight (n 8) and underweight (n 5) 'large-eating' men. For the matched groups of 'large-' and 'small-eaters' there were no differences in resting metabolic rate (RMR) measurements but during controlled daily activities there was a small but significant increase (P < 0.05) in energy expenditure in the 'large-eaters'. These results contrast with those obtained for the unmatched groups where energy requirements were about 10% (P < 0.01) higher in the underweight 'large-eaters' at rest but were not different during the more energetic (walking) activities. However, after adjustment for differences in FFM between these two groups, the resting energy expenditures of the 'large-eaters' (82.54 (SE 1.51) J/kg FFM per min) were similar to those of the 'small-eaters' (81.87 (SE 1.51) J/kg FFM per min). Oral temperatures were significantly higher in the matched (0.35-0.65 degrees) and unmatched (0.7-0.9 degrees) 'large-eaters' both at rest and during the different activities, but the thermic effect of food (50 kJ/kg FFM) was one fifth lower (not significant) in both groups of 'large-eaters'. These results provide little evidence for any major metabolic differences between groups of 'large-eating' and 'small-eating' men.

Adult↗

Hemangioma of spleen with spontaneous, extra-peritoneal rupture, with associated splenic tuberculosis--an unusual presentation.

We report a case of unusual presentation of a patient with hemangioma of the spleen. The patient had presented with recurrent gastric hemorrhage and significant weight loss, due to ruptured hemangioma of the spleen and associated splenic tuberculosis. The true nature of the lesions remained a diagnostic dilemma despite complete radiological workup and review of literature.

Adult↗

Postoperative bile duct strictures: ultrasound and endoscopic retrograde cholangiopancreatography/percutaneous transhepatic cholangiography evaluation.

This retrospective study was undertaken to assess the role of ultrasound (US) and to compare it with endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC) in the evaluation of post-operative common bile duct (CBD) strictures. Seventy-four patients with postoperative CBD strictures were evaluated by ERCP and/or PTC. Of these, US scans were available in 52 patients. Ultrasound findings of CBD strictures were: proximal dilatation of CBD with smooth tapering stenosis (41%); abrupt cut off of CBD (18%); and echogenic nodule, without acoustic shadowing, in 16%. Of the remainder, mild proximal dilatation of the CBD was seen in 6%, and 19% of the patients had normal US scans.

Adult↗

Neural networks for molecular sequence classification.

A neural network classification method has been developed as an alternative approach to the search/organization problem of large molecular databases. Two artificial neural systems have been implemented on a Cray supercomputer for rapid protein/nucleic acid sequence classifications. The neural networks used are three-layered, feed-forward networks that employ back-propagation learning algorithm. The molecular sequences are encoded into neural input vectors by applying an n-gram hashing method or a SVD (singular value decomposition) method. Once trained with known sequences in the molecular databases, the neural system becomes an associative memory capable of classifying unknown sequences based on the class information embedded in its neural interconnections. The protein system, which classifies proteins into PIR (Protein Identification Resource) superfamilies, showed a 82% to a close to 100% sensitivity at a speed that is about an order of magnitude faster than other search methods. The pilot nucleic acid system, which classifies ribosomal RNA sequences according to phylogenetic groups, has achieved a 100% classification accuracy. The system could be used to reduce the database search time and help organize the molecular sequence databases. The tool is generally applicable to any databases that are organized according to family relationships.

Base Sequence↗

A single point mutation is the cause of the Greek form of hereditary persistence of fetal haemoglobin.

In normal humans the fetal stage-specific gamma-globin genes are silenced after birth and not expressed in the adult. Exceptions are seen in cases of hereditary persistence of fetal haemoglobin (HPFH). These are clinically important because the elevated levels of gamma-globin can alleviate beta-thalassaemia and sickle cell anaemia. One class of mutations is associated with point mutations in the promoter of the gamma-globin genes (non-deletion HPFH), whereas others seem to be caused by large deletions 3' to the gamma-globin genes. To test whether the point mutation found in the Greek non-deletion HPFH (guanine to adenine at nucleotide position -117) is the cause of the raised gamma-globin levels in the adult stage and is not just a linked polymorphism, we engineered this mutation into a gamma-globin gene. When this gene was introduced into mice, the presence of the -117 mutation results in persistence of gamma-globin expression at a high level and a concomitant decrease in beta-globin expression in fetal and adult mice. We show that these changes correlate with the loss of binding of the transcription factor GATA1 to the gamma-globin promoter, suggesting that it may act as a negative regulator of the gamma-globin gene in adults.

Animals↗

Development of astroglial cells in the proliferative matrices, the granule cell layer, and the hippocampal fissure of the hamster dentate gyrus.

The histogenesis of the hamster dentate gyrus was studied with light and electron microscopy and antisera against the astrocyte-associated antigens vimentin and GFAP, in order to follow the differentiation of radial glial cells and astrocytes. The formation of the stratum granulosum is preceded by the establishment of successive dentate matrices, which are formed by cells that leave the ventricular neuroepithelium and occupy positions above the fimbria (suprafimbrial), below the pial surface (subpial), and within the dentate hilus (hilar dentate matrix). The subpial dentate matrix invades the marginal zone of that region of the cerebral wall, where the stratum granulosum will later develop. From the beginning of its existence on embryonal day 13 (E13) up to its disappearance about postnatal day 7 (P7), it is characterized by a high content of GFAP-positive cells and mitoses. This indicates early gliogenesis in the dentate anlage, long before the appearance of the stratum granulosum. Many of the bipolar GFAP-positive cells are oriented parallel to the pial surface and have focal contacts to the pial basement membrane. The establishment of the subpial dentate matrix splits the primordial radial glial scaffold of the hippocampal/dentate anlage into two bundles: 1) the suprafimbrial bundle that retains its original radial position between ventricle and pial surface; and 2) the dorsal glial bundle that traverses the ventral tip of the pyramidal cell layer of future CA3. The latter is pushed dorsolaterally, away from the pial surface, by the enlargement of the subpial dentate matrix and, later, by the suprapyramidal blade. The latter emerges around birth as small radial columns of granule cells located between the bent basal parts of the ventralmost fibers of the dorsal glial bundle and the subpial dentate matrix. From the beginning of its existence it is traversed by unipolar "secondary" radial glial fibers that appear to originate from the subpial dentate matrix. Both the supra- and the infrapyramidal blades seem to elongate by the addition of postmitotic granule cells and "secondary" radial glial cells from the subpial dentate matrix to the growing end of the primordial stratum granulosum. The hilar dentate matrix that is localized in the prospective hilar region, inside the growing stratum granulosum, also contains glial cells that seem to be incorporated into the stratum granulosum. The dentate gyrus is demarcated from the CA1 region of the hippocampus proper by GFAP-positive cells that populate the hippocampal fissure, and that also originate from the subpial dentate matrix.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Destruction of meningeal cells over the medial cerebral hemisphere of newborn hamsters prevents the formation of the infrapyramidal blade of the dentate gyrus.

Meningeal cells participate in the development of the cerebellum both by stabilizing the extracellular matrix of the pial surface and by organizing the radial glial scaffold and the lamination of the cerebellar cortex. In the present study we investigated possible influences of meningeal cells on the development of the dentate gyrus, whose ontogenesis has many similarities to that of the cerebellum. Meningeal cells were selectively destroyed by injecting newborn hamsters with 25 micrograms 6-hydroxydopamine (6-OHDA) into the interhemispheric fissure. Twenty-four hours postinjection (p.i.) the meningeal cells over the medial cerebral hemispheres were completely destroyed. Thirty days p.i. the infrapyramidal blade of the dentate gyrus was almost completely missing, while the suprapyramidal blade was hypertrophied, extending with its medial tip almost up to the medial surface of the cortex. In order to ascertain that this maldevelopment was caused by the destruction of meningeal cells, another group of hamsters was pretreated with normetanephrine (NMN) which inhibits the extraneuronal uptake of 6-OHDA into meningeal cells. In this group the meningeal cells were unaffected by the treatment, and the morphology of the dentate gyrus was normal 30 days p.i. of 6-OHDA plus NMN. When the meningeal cells were destroyed in later stages of development (postnatal days 1-5), alterations of the dentate gyrus could be induced only up to the fourth postnatal day; thereafter, 6-OHDA treatment left it unchanged. This indicates a critical period of meningeal cell influence that coincides with the period of existence of the subpial dentate matrix. Analysis of the time course of the defective development revealed that in the first 5 days p.i. 1) meningeal cells over the medial cerebral hemisphere were destroyed and removed, 2) the pial basement membrane over both the dentate anlage and the diencephalon thinned and ruptured, and the adjacent brain parts fused focally, 3) many cells of the subpial dentate matrix disappeared from their subsurface position, 4) the number of "immature" cells increased in the hilus and the subgranular zone of the suprapyramidal blade, 5) the suprapyramidal blade elongated and thickened considerably, while the infrapyramidal blade did not form. Beyond 5 days p.i. those parts of the pial surface of the dentate anlage that had not fused with the diencephalon were repopulated with meningeal cells. This reappearance of meningeal cells was accompanied by 1) the restitution of the normal morphology of the basement membrane, 2) the reappearance of neuronal and glial cells below the pial surface, and 3) the formation of fragments of the infrapyramidal blade which later developed a normal appearing lamination.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Cooperation of proto-signals for nuclear accumulation of estrogen and progesterone receptors.

Multiple proto-signals (p-NLSs) for nuclear targeting, none of which suffices on its own, cooperate in the estrogen (ER) and progesterone (PR) receptors. In the ER, an estrogen-inducible p-NLS was found in the hormone binding domain (HBD), in addition to three lysine/arginine-rich motifs resembling prototype constitutive nuclear localization signals (NLSs). The inducible and the constitutive ER p-NLSs cooperate in the presence of estrogen and hydroxy-tamoxifen, but not in the presence of ICI 164,384. In the PR, three p-NLSs, two of which are located within and directly adjacent to the second zinc finger, cooperate with each other and a weak hormone-inducible p-NLS in the PR HBD. No 'masking' of p-NLSs by the HBD was observed for ER and PR, while the ligand-free glucocorticoid receptor HBD inhibited the activity of both homologous and heterologous NLSs. Nuclear co-translocation experiments indicated that in vivo the stability of ER and PR dimers is hormonally controlled, but that, in the absence of the cognate ligand, ER dimers are more stable than PR dimers. This is likely to account for the differential hormone requirement of ER and PR DNA binding in vitro.

Amino Acid Sequence↗

Regrowth of PNS axons through grafts of the optic nerve of the Browman-Wyse (BW) mutant rat.

We have examined the behaviour in vivo of regenerating PNS axons in the presence of grafts of optic nerve taken from the Browman-Wyse mutant rat. Browman-Wyse optic nerves are unusual because a 2-4 mm length of the proximal (retinal) end of the nerve lacks oligodendrocytes and CNS myelin and therefore retinal ganglion cell axons lying within the proximal segment are unmyelinated and ensheathed by processes of astrocyte cytoplasm. Schwann cells may also be present within some proximal segments. Distally, Browman-Wyse optic nerves are morphologically and immunohistochemically indistinguishable from control optic nerves. When we grafted intact Browman-Wyse optic nerves or 'triplets' consisting of proximal, junctional and distal segments of Browman-Wyse optic nerve between the stumps of freshly transected sciatic nerves, we found that regenerating axons avoided all the grafts which did not contain Schwann cells, i.e., proximal segments which contained only astrocytes; regions of Schwann cell-bearing proximal segments which did not contain Schwann cells; junctional and distal segments (which contained astrocytes, oligodendrocytes and CNS myelin debris). However, axons did enter and grow through proximal segments which contained Schwann cells in addition to astrocytes. Schwann cells were seen within grafts even after mitomycin C pretreatment of sciatic proximal nerve stumps had delayed outgrowth of Schwann cells from the host nerves; we therefore conclude that the Schwann cells which became associated with regenerating axons within the grafts of Browman-Wyse optic nerve were derived from an endogenous population. Our findings indicate that astrocytes may be capable of supporting axonal regeneration in the presence of Schwann cells.

Animals↗