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Biomedical subjects

M Berry

Publications and source records attributed to M Berry.

At least 325 records · Page 18Linked to original sources

Regeneration of axons in the mouse retina after injury.

It is generally accepted that most axons in the mammalian CNS show only transient growth in response to injury, and numerous hypotheses have been advanced to account for this phenomenon. Detailed knowledge of the time-course and extent of this so-called 'abortive regeneration' is, however, surprisingly lacking. The retina of the adult albino mouse provides a convenient system in which to quantify the response of central axons to injury, since the retina can be prepared as a whole mount, allowing silver-impregnated axons to be followed along their entire course. Using this experimental model, sprouting of injured axons was observed as early as 14 h post lesion (hpl) with rapid growth (20 micrometers/day on average) continuing until 10 dpl. Thereafter, a decline in the overall growth rate was observed, presumably regenerated sprouts began to degenerate. However, not all axons showed this abortive response: numerous unfasciculated axons continued in random growth until at least 100 dpl. One possible interpretation of these results is that the concept of abortive regeneration of injured axons is untenable in regions of the CNS which are lacking in myelin.

Animals↗

Experimental studies on cerebellar foliation. I. A qualitative morphological analysis of cerebellar fissuration defects after neonatal treatment with 6-OHDA in the rat.

The present report describes the natural history of defective cerebellar fissuration in the rat after neonatal treatment with 6-hydroxydopamine (6-OHDA). Within 24 hours after an intracisternal (IC) injection of 100 micrograms 6-OHDA cerebellar pial fibroblasts degenerated almost completely and were phagocytosed b macrophages within 2-5 days postinjection (dpi) leaving the cerebellar surface denuded of pia. Bergmann glia end feet at first exhibited morphological signs of gliosis and later formed new sprouts that penetrated the basal lamina and grew into the subarachnoid space covering regenerating pial fibroblasts and also invading ectopic colonies of external granular layer (EGL) cells. Breaches in the basal lamina appeared after the pial fibroblast had been destroyed and were confined to areas where Bergmann glia end feet were absent and where EGL cells were opposed to the basal lamina. EGL cells escaped through these fractures into the subarachnoid space in the fissures, where they proliferated to form large colonies of granule and stellate cells. In those fissures in which EGL ectopia featured, opposing folia fused and fissures were lost. These findings suggest that pial fibroblasts and the basal lamina have an important role in maintaining lobular partition during development of the cerebellum, in establishing cerebellar fissures, and in consolidating Bergmann glia-EGL cell relationships as a prerequisite for orderly migration of EGL cells.

Animals↗

The effects of refeeding after varying periods of neonatal undernutrition on the morphology of Purkinje cells in the cerebellum of the rat.

Undernutrition of the rat for the first 30 days of postnatal life is known to permanently alter Purkinje cell (PC) dendritic morphology. The effects of earlier nutritional rehabilitation have not previously been determined. Neonatal rat pups were undernourished by limiting their access to the lactating dam. After 10, 15, or 20 days of food restriction, animals were either killed for histological comparison with normally fed controls, or provided with ad libitum food until 80 dpp, and then killed. Network analysis of Golgi Cox impregnated PCs from the undernourished animals revealed alterations in dendritic length, segment frequency, and branching pattern, which first became apparent at 15 dpp, accompanied by a reduction in the number of granule cells (GCs) per PC. If undernourished animals were refed from 10 or 15 days, however, the total lengths and segment frequencies of their PC trees were indistinguishable from those of controls at 80 dpp, although the 15-day group showed persistent topological alterations. The GC:PC ratios of these refed groups were also found to be similar to those of the controls. In animals refed after 20 days of undernutrition, network size remained reduced, as did the GC:PC ratio. The different degrees of recovery of PC dendritic field parameters recorded in the refed animals could be related either to enhanced GC replication afforded by refeeding, or to the existence of intrinsic mechanisms which limit the growth capacity of the PC dendrites.

Animals↗

The potentiation of adenine toxicity to Chinese hamster cells by coformycin: suppression in mutants with altered regulation of purine biosynthesis or increased adenylate-deaminase activity.

When added to medium containing coformycin (2 microM or above), adenine is lethal to Chinese hamster fibroblasts at the concentration inhibiting de novo purine biosynthesis (Debatisse and Buttin, '77b). Rescue by hypoxanthine suggested that cells die of IMP starvation when the analog can turn off deamination of both adenosine and adenylate. As predicted from this hypothesis, two classes of variants resistant to the mixture of coformycin + adenine have been isolated: Class 1 variants have altered control of de novo IMP biosynthesis; they fall into two subclasses on the basis of their resistance to adenosine. Class 2 variants have a 6-10-fold increased level of AMP-deaminase (E.C.: 3.5.4.6); their growth in the selective medium is temperature-dependent, a property accounted for by the observation that cell growth in the presence of coformycin imposes a gradual thermodependent decay of specific AMP-deaminase activity in both wild-type and variant lines. This control by coformycin of AMP-deaminase activity is unaltered in mutants deficient in the four activities of adenosine-kinase. APRT, HGPRT and deoxycytidine-kinase. Most of the resistant variants are unstable and exhibit either increased or reduced resistance, depending on prolonged growth in selective or normal medium.

AMP Deaminase↗

Cells involved in the immune response. XXX. An evaluation of the different assays to demonstrate rabbit spleen plaque-forming cells. Enhancement of the assay by anti-target cell antibodies.

Four different procedures for the detection of rabbit spleen plaque-forming cells (PFC) directed toward the sheep erythrocyte (SRBC) antigen were evaluated in terms of their sensitivity. These included the conventional localized hemolysis in gel (LHG) assay, the thin-layer LHG assay, the LH assay using a monolayer of the target SRBC erythrocytes and the localized hemolysis in liquid phase (Cunningham) assay. The latter assay consistently proved to be the most sensitive assay. The sensitivity of this latter assay was further improved by incorporating preformed IgG or IgM antibodies directed toward the target erythrocytes, in subhemolytic concentrations, into the assay. This antibody-enhanced plaque assay in liquid medium is 20-50 times more sensitive than the conventional LHG assay.

Animals↗

Alveolar-capillary membrane permeability. Correlation with functional, radiographic, and postmortem changes after fluid aspiration.

An index of permeability of the alveolar-capillary membrane was derived from the relative extraction from the lung into arterial blood of 2 tracers, 125I-antipyrine and 51Cr-ethylenediaminetetraacetate. The effect on this index of aspirating 2 ml of isotonic saline, distilled water, or 10(-1) M hydrochloric acid per kg of body weight was studied in 3 groups of rabbits. The severity and time course of changes in the permeability index were correlated with changes in lung mechanics, gas exchange, serial chest roentgenograms, ratio of extravascular lung water to dry weight, and histologic findings. Aspiration of saline produced no change in the permeability index; aspiration of water produced a large mean +/- SEM increase in the index, from a baseline of 0.025 +/- 0.002 to 1,050 +/- 0.054 (P less than 0.001), but this value returned to baseline 15 min later. After hydrochloric acid, the permeability index increased from a baseline of 0.027 +/- 0.003 to 1.068 +/- 0.098 (P less than 0.005), with no evidence of resolution after 60 min. Changes in lung mechanics, gas exchange, and roentgenograms were smallest after aspiration of distilled water and greatest after aspiration of hydrochloric acid. The functional changes after aspiration of water and saline recovered at a rate proportional to the known clearance rates of these liquids from the lung. The changes after hydrochloric acid either showed no tendency toward recovery or, in the case of the roentgenograms, worsened with time. There were no detectable histologic abnormalities or an increase in the ratio of extravascular lung water to dry weight after aspiration of water or saline, but there were extensive histologic abnormalities and a 70 per cent increase in lung water after acid. The increase in the permeability index after aspiration of water was too transient to exert a deleterious effect. In contrast, the persistence of the increase in the permeability index after hydrochloric acid was associated with persistent functional changes attributable to the considerable increase in lung water.

Animals↗

A reappraisal of the effects of ACTH on the response of the central nervous system to injury.

ACTH possesses powerful immuno-suppressive properties and also retards healing by inhibiting fibroblast proliferation and the deposition of collagen. In the present work this hormone was used to test both the 'barrier' and 'immune' hypotheses relating to the failure of CNS regeneration after injury, dosages being administered which had been found to stimulate maximal adrenal production of glucocorticoids in control animals. Although the scarring in the CNS and the systemic humoral and cellular immune responses were significantly depressed, no increase in CNS axon growth was noted, even when large doses of thyroxine were added. We conclude that both 'immune' and 'barrier' hypotheses should be rejected, and that the beneficial effects of thyroxine treatment reported by some workers are not substantiated.

Adrenocorticotropic Hormone↗