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Retinal ganglion cells (RGCs) in rats were retrogradely labeled with the fluorescent tracer Fluorogold (FG) and subjected to GAP-43 and c-JUN immunocytochemistry to identify those RGCs that are capable of regenerating an axon. After optic nerve section (ONS) and simultaneous application of FG to the nerve stump (group 1 experiments), GAP-43 immunoreactive RGCs (between 2 and 21 days after ONS) always represented a subfraction of both FG-labeled (i.e., surviving) RGCs and RGCs exhibiting c-JUN. GAP-43 immunoreactive RGCs represented 22% of RGCs normally present in rat retinae and 25% of surviving RGCs at 5 days after ONS but were reduced to 2% and 1%, which is 6% and 5% of survivors at 14 and 21 days, respectively. In animals that received a peripheral nerve (PN) graft after ONS (group 2 experiments), RGCs with regenerating axons were identified by FG application to the graft at 14 and 21 days. When examined at 21 and 28 days, all FG-labeled RGCs exhibited GAP-43 immunoreactivity, and FG/GAP-43-labeled RGCs were 3% and 2% of those present in normal rat retinae. In relation to surviving RGCs GAP-43 immunoreactive RGCs represented 10% at both time points. FG-/GAP-43-labeled RGCs also exhibited c-JUN, but c-JUN immunoreactive RGCs were at both time points at least twice as numerous as FG-/GAP-43-labeled RGCs. These data suggest that regenerating axons in PN grafts derive specifically from GAP-43 reexpressing RGCs. Appearance of GAP-43 immunoreactivity may therefore identify those RGCs that are capable of axonal regeneration or sprouting.

In the CNS of mammals, axonal regeneration is limited by inhibitory influences of the glial and extracellular environment. Myelin-associated inhibitors of neurite growth, as well as some properties of so-called 'reactive astrocytes' which make the environment non-permissive for axonal growth, contribute to the inhibitory nature of the mammalian CNS. Furthermore, mechanisms for effective removal or neutralization of inhibitory components of cell debris are lacking in the mature mammalian CNS. However, in a permissive environment, mammalian CNS axons are able to regrow, to recognize target areas and to re-establish functional synapses with target neurones. Moreover, recent observations suggest that guiding molecules, like those required for axon guidance in the developing CNS, become expressed after lesions. Regenerating CNS axons seem to be able to recognize such guidance cues. Thus, even regenerating CNS axons of mammals might ultimately succeed in re-establishing topographically ordered functional synapses in their target regions.

In adult rats, the distance between the site of axotomy and the cell body influences the ability of retinal ganglion cells (RGCs) to survive and regenerate an axon. Optic nerves of adult rats were transected 2 mm or 6 mm from the optic bulb and RGCs labeled with the fluorescent marker fluorogold. The time course of c-JUN expression was monitored immunocytochemically between 3 days and 4 weeks after axotomy. c-JUN expression began later and declined faster after distal axotomy than after proximal transection of the optic nerve. However, at the same time significantly more RGCs survived after distal than after proximal axotomy 3 and 4 weeks after axotomy. These findings suggest that survival and expression of c-JUN in rat RGCs are independently regulated by the length of the optic nerve stump after lesion.

Several types of lesions of the mature central nervous system (CNS), such as craniocerebral trauma or spinal cord trauma, may initiate secondary cascades, which may cause damage to primarily uninjured neurons. The exact mechanisms which cause neuronal cell death are still unknown. It has been suggested that retrogradely transported target-derived neurotrophic factors which are necessary for neuronal survival might be lacking after certain types of lesions. On the other hand, neurons might be damaged by calcium-overload resulting from excessive release of excitatory amino acids (EAAs) after trauma. The present review summarizes current concepts of post-traumatic neuronal cell damage with a focus on the putative neuroprotective role of calcium channel blockers and their interaction with glutamate mediated cytotoxicity, neurotrophic factors and free radicals.

To determine mechanisms of structural plasticity in adult CNS neurons, we investigated the expression of immediate early genes (IEGs) in the rat retina. Gene products of different IEG families (JUN and FOS proteins) and cAMP-responsive element binding protein (CREBP) were examined by immunohistochemistry under three different paradigms. Normal rats which were not axotomized were compared with axotomized animals, were retinal ganglion cells (RGCs) were axotomized by intraorbital optic nerve cut and retrogradely labeled with fluorogold (FG). Under these circumstances, RGCs show only transient sprouting, followed by continuous retrograde RGC degeneration. In the third group, after the optic nerve lesion, adult rats additionally received a sciatic nerve graft to the transected optic nerve stump. This allows some RGCs to regenerate an axon into the grafted nerve. In both groups, the time course of RGC survival and JUN, CREB, and FOS protein expression was monitored. In normal animals, JUN-Immunoreactivity (JUN-Ir) was not detectable in the retinal ganglion cell layer. JUN-Ir was induced in about 70% of all FG-positive RGCs 5 days after axotomy. The expression of JUN-Ir stated to decline 8 days after axotomy. Only a few JUN-Ir-positive RGCs were found after 2 weeks. In transplanted animals, however, the numbers of JUN-Ir-positive RGCs were significantly higher 2 and 3 weeks after transplantation compared to animals that exclusively received axotomy. Furthermore, in grafted rats, about 70% of the regenerating RGCs expressed JUN-Ir 2 weeks after grafting as compared to only 38% JUN-positive RGCs among the surviving but not regenerating RGCs. In normal animals CREBP-Ir was constitutively expressed in nearly all cells of the retinal ganglion cell layer. The decline in number of CREBP-Ir-positive cells paralleled the axotomy-induced RGC death. FOS-Ir-positive cells were not found in the ganglion cell layer at any time. These results demonstrate a selective and transient JUN expression of RGCs after axotomy which is sustained during axonal regeneration. This suggests that sciatic nerve grafts are able to regulate the expression of JUN proteins in axotomized RGCs of adult rats.

We have studied the glial response to optic nerve axotomy in vitro. Glial cells were obtained from normal and crush-axotomized optic nerves. In cultures from axotomized nerves, large numbers of astrocytes, oligodendrocyte progenitors and mature oligodendrocytes were found. Significantly fewer astrocytes and oligodendrocyte progenitors were present in cultures from normal nerves, mature oligodendrocytes did not occur. Proliferation and maturation of oligodendrocyte progenitor cells was only observed in cultures from axotomized nerves, suggesting the regulatory influence of blood-derived factors which are not present in normal nerves after in vitro axotomy. These data show that optic nerve injury enhances the ability of astrocytes, oligodendrocytes and their precursors to survive and/or proliferate in vitro.

During development of the vertebrate visual system, an orderly projection of ganglion cells from the retina onto the superior colliculus (SC) is established. Mechanisms that might govern this process include the coordinated action of guidance and corresponding receptor molecules that are specifically distributed on the axons and their targets. In birds and mammals, information for axonal guidance and targeting appears to be confined to the time when the retinocollicular projection is being formed. Here we show that putative guidance activities for temporal and nasal retinal axons, which are not detectable in the normal adult SC, appear after optic nerve transection in adult rats. Both embryonic and adult retinal axons are able to respond to these guiding cues, although the guidance activities detectable in the deafferented adult rat SC might be different from those found during development. These findings imply that it might be possible to reestablish an ordered projection after lesions in the adult mammalian visual system.

In order to determine the origin of brain phagocytes brain slices and optic nerve segments from adult Lewis rats were transplanted into the peritoneal cavity of syngenic recipients. The specimens were contained in Millipore diffusion chambers fitted with membranes of either 0.22 or 5.0 microns pore size. The either blocked or allowed the access of non-resident cells. Each recipient rat received both a 0.22 and 5.0 microns pore chamber. Later (3-16 days), the specimens were recovered and analyzed by monoclonal antibody techniques and electron-microscopy. Endothelia, GFAP+ astrocytes, ED1-/ED2+/RCA-1+/OX-6-perivascular cells and ED1-/ED2-/RCA-1+/lysozyme--microglia were found to have survived the procedure. Cells of the macrophage phenotype (ED1+/ED2+/RCA-1+/lysozyme+/vimentin+ with phagocytic vacuoles), however, were only found in large numbers in specimens kept within 5.0 microns pore size chambers, giving access to non-resident cells, and were exceedingly rare in specimens from 0.22-micron pore chambers. It has been concluded that the majority of brain phagocytes found after lesions do not originate from microglia or perivascular monocytic cells, but rather from invading cells.

After axotomy most central nervous neurons including retinal ganglion cells (RGCs) die in a few weeks, although their somata are not injured. This neuronal death could be due to lack of retrogradely transported target derived neurotrophic factors or due to a calcium overload after excessive release of excitatory amino acids from dying cells. Flunarizine, as a potent blocker of voltage dependent Ca2+ channels and in higher concentration being an inhibitor of the Ca2+/calmodulin-dependent protein kinase II, is able to mimic the neurotrophic effect of NGF on dorsal root ganglion (DRG) neurons. To examine its neuroprotective value in the central nervous system (CNS), flunarizine (5 mg/kg body weight) was given daily to rats after unilateral axotomy of the optic nerve. The density of retrogradely labelled retinal ganglion cells (RGCs) was determined 14 days after axotomy. It could be demonstrated that flunarizine significantly enhanced RGC survival after axotomy in adult rats (P < 0.001; 1065 +/- 142 vs. 922 +/- 237 RGCs/mm2).

Segments from adult fish and rat retinae were explanted on myelin-marker expressing oligodendrocytes derived from the regenerating goldfish optic nerve. Fish axons grew in high density and even rat retinal axons regenerated to considerable length on the surface of the fish oligodendrocytes, suggesting that this type of fish glia has axon-growth promoting surface components that exert their influence across species boundaries. One interesting surface component of the fish oligodendrocytes as demonstrated here is the E 587 antigen, which is related to the L1 family of cell adhesion molecules. In long term cocultures of oligodendrocytes and retinal axons, the fish glial cells were found to enwrap rat axons. This suggests that the oligodendrocytes of the regenerating goldfish optic nerve/tract may, despite striking differences, represent the equivalent to mammalian optic nerve oligodendrocytes.

The ability of adult rat retinal ganglion cell (RGC) axons to reinnervate normal target regions was examined in vitro. In co-culture experiments, adult rat retinal explants were placed adjacent to fetal rat midbrain sections that contained the superior colliculus (SC) which is the main target for RGC axons. Adult rat RGCs regrew axons over more than 500 microns on a polylysine-laminin substrate to reach the co-cultured explants. By using neurofilament immunohistochemistry and the fluorescent dye DiI for anterograde and retrograde tracing, it was shown that (1) adult rat RGCs with a stereotyped morphology survived in explant cultures for more than 4 weeks in the presence of fetal midbrain explants, (2) regenerating RGC axons preferentially terminated within midbrain target regions, and (3) RGCs formed functional synapses. In addition, the maturation of the SC region in midbrain explants was examined histologically and ultrastructurally to demonstrate appropriate target development.

Goldfish and rat optic nerves were cut and crushed, respectively, and the expression of the transcription factor proteins c-JUN, JUN B, JUN D, c-FOS, FOS B, KROX-24, and CREB was investigated in retinal ganglion cells (RGCs) by immunocytochemistry. Immunoreactivities (IRs) were followed up to 350 days in the goldfish and up to 22 days in the rat. In RGCs of untreated goldfish and rats, all JUN, FOS, and KROX proteins were absent whereas CREB was constitutively expressed. After optic nerve cut in goldfish, a JUN-like immunoreactivity (JUN-IR) appeared in a small number of RGCs of central retina after 24 h, reached a maximum within 5 days, declined after 30 days, and was on a half-maximal level after 50 days. Between 100 and 200 days, JUN-IR was only visible in a few RGCs and was completely absent after 350 days. Specific antibodies against c-JUN, JUN B, and JUN D gave no distinct immunoreactive signal. Thus, we could not determine which member of the JUN family contributed to the JUN-IR. The expression of CREB declined after 5 days. The number of CREB-labeled RGCs was reduced (not significant) and the intensity of labeling faded out. After 50 days, CREB-IR had returned to basal level. c-FOS, FOS B, and KROX-24 could not be detected in goldfish RGCs following optic nerve cut. After optic nerve crush in the rat, c-JUN, JUN D, and KROX-24 appeared in a substantial number of RGCs after 24 h, had a maximal expression after 5 days, and strongly declined after 8 days. c-JUN and KROX-24 were completely absent after 22 days whereas JUN D was still present in a few rat RGCs. The number of CREB-labeled RGCs decreased after 5 days and had declined by 50% after 22 days. Expression of JUN B, c-FOS, FOS B could not be detected in rat RGCs after optic nerve crush. Our data demonstrate that the decrease of CREB and the increase of JUN and KROX-24 transcription factors precedes and parallels both the alteration of de novo protein synthesis and the axonal sprouting, which are long lasting in goldfish and transient in rat.

In contrast to the situation in mammals and birds, neurons in the central nervous system (CNS) of fish--such as the retinal ganglion cells--are capable of regenerating their axons and restoring vision. Special properties of the glial cells and the neurons of the fish visual pathway appear to contribute to the success of axonal regeneration. The fish oligodendrocytes lack the axon growth inhibiting molecules that interfere with axonal extension in mammals. Instead, fish optic nerve oligodendrocytes support--at least in vitro--axonal elongation of fish as well as that of rat retinal axons. Moreover, the fish retinal ganglion cells re-express upon injury a set of growth-associated cell surface molecules and equip the regenerating axons throughout their path and up into their target, the tectum opticum with these molecules. This may indicate that the injured fish ganglion cells reactivate the cellular machinery necessary for axonal regrowth and pathfinding. Furthermore, the target itself provides positional marker molecules even in adult fish. These marker molecules are required to guide the regenerating axons back to their retinotopic home territory within the tectum.

We have examined morphological changes of retinal ganglion cells (RGCs) during postnatal development in albino rats. Somatic diameter, dendritic field diameter, and branching frequencies of RGCs of normal rats were compared with those of animals that had received bilateral lesions of the tectum immediately after birth. Bilateral lesions of the tectum at P1 (first postnatal day) induced a dramatic increase in RGC death during the time of naturally occurring cell death in the first postnatal week. RGC densities in adult experimental animals were found to be reduced to about 55% of normal. RGCs of normal and operated animals were retrogradely stained with crystals of the fluorescent dye DiI, which was applied to the optic disc of flat mounted and fixed retinae. In normal rats, the somatic and the dendritic field diameters of the RGCs increased and the branching frequency of type I and III RGCs decreased from P1 to P14. By P14, neither the somatic diameter nor the dendritic field size had yet reached adult values and the branching frequencies were still higher than those of adult rat RGCs. In animals with bilateral lesions of the tectum, all cell types showed an increase in somatic sizes, and in type I and II RGCs an expansion of dendritic territories could be observed. The branching frequencies, however, were significantly lower than those of normal rats of the same age. The dendritic morphology in type III RGCs in operated animals was not significantly different from controls. These findings demonstrate a potential plasticity of type I and II RGCs, which respond to a loss of neighbouring cells by expansion of their dendritic field during postnatal development.

We have examined the influence of normal and precrushed ("conditioned") sciatic nerve grafts on the survival and axonal growth of retinal ganglion cells (RGCs) in adult rats. Normal sciatic nerves (group A) or sciatic nerves which had been crushed 1 week before transplantation (group B, conditioned grafts) were used as grafts. The nerves were removed and sutured to the proximal stump of intraorbitally axotomized optic nerves. Neuronal survival and axon growth were determined by counting the numbers of surviving, DiI-prelabled RGCs, cresyl violet-stained RGCs and the numbers of axons which had grown into the grafts 3 and 6 months after transplantation. Counting of axons was performed by combined use of light and electron microscopy. We observed that the use of conditioned grafts (group B) significantly enhanced RGC survival and axonal regrowth as compared to normal grafts 3 months after transplantation. Six months after grafting, RGC survival (as determined in DiI-stained retinae) and axonal growth were not significantly different in both groups. These results suggest that the functional status of a peripheral nerve used for grafting in the CNS influences neuronal viability and axonal reelongation especially during the first 3 months after grafting. Very long-term RGC survival, however, may be determined by functional reconnection of regenerating RGC axons rather than by the graft itself.

We have established an in-vitro coculture-system of adult rat retina with fetal midbrain explants to examine whether regenerating central nervous system axons are still able to recognize appropriate target neurons. Our results show that the retinal ganglion cell axons regenerate their axons and reinnervate the retino-recipient areas of cocultured fetal midbrain slices after one to seven weeks in-vitro. Functional connections as defined by electrophysiological criteria are detected only within these areas.

Between 1983 and 1990, HELLP syndrome was diagnosed in 19 of 201 patients with preeclampsia. In addition to the characteristic changes in laboratory values, severe edema and proteinuria were found in almost all cases. Upper abdominal pain was the most common subjective symptom and, together with a reduced thrombocyte count, was often a first sign of HELLP syndrome. In some cases blood pressure was only slightly increased. Maternal and infant morbidity were significantly increased. Premature termination of labor was usually necessary, in most cases due to maternal pathology. The incidence of intrauterine dystrophy and premature delivery far exceeded the norm. Early detection of HELLP syndrome is crucial, and interdisciplinary cooperation is a key factor in achieving this goal.

Schwann cell cultures provide a highly favorable substrate for retinal ganglion cell (RGC) survival and axon growth in vitro (Bähr and Bunge, Exp Neurol 106:27, 1989; Hopkins and Bunge, Glia 4:46, 1991). In this report we have extended former studies to obtain axon regeneration, long-term survival, and myelination of adult rat RGC axons in co-cultures of retinal explants with purified Schwann cells. By using modified co-culture conditions, we observed myelination of regenerating adult RGC axons by Schwann cells after 3-4 weeks in vitro. Myelination was associated with a one-to-one Schwann cell-axon relationship, characteristic of the formation of peripheral myelin. Under culture conditions that supported myelination, long-term survival (more than 12 weeks) of a small population of RGCs was observed. These findings highlight the remarkable ability of Schwann cells to support long-term survival of adult rat RGCs in the absence of either central nervous system (CNS) target tissue or other peripheral nervous system (PNS) components. This tissue culture system may serve as a model for the systematic study of the molecular mechanisms which are involved in axon regeneration and myelination of adult CNS neurons.

The effect of a single dose of 200 mg dilevalol, beta-adrenoceptor blocker with additional vasodilating properties, and 200 mg oxprenolol on haemodynamic changes induced by emotional stress have been compared in 12 male young Caucasian patients with newly diagnosed labile hypertension. No difference was noted in the stress-induced increase of total peripheral resistance (TPR) following administration of the two substances (11% versus 6%). However, dilevalol revealed a vasodilating action by decreasing TPR at rest (from 1004 to 951 dyn.s.cm-5) and diastolic blood pressure (BP) (from 87 to 75 mm Hg) whereas TPR at rest remained unchanged after the intake of oxprenolol.

The effects of optic nerve crush on adult rat retinal glia activation were studied in vitro. In adult rats the optic nerves were crushed and the corresponding retinae were explained 5 to 7 days later and cultured in vitro. The glial response of retinae with precrushed optic nerves was compared to the glial response of retinae without prior optic nerve crush. As a consequence of crush-axotomy more glial cells migrated out from retinal explants and covered significantly larger areas of the substratum than glia from noncrushed retinae. Migration of immunohistochemically distinguishable Vimentin-positive Müller cells and glial fibrillary acidic protein-positive astrocytes could be observed in both types of cultures. Astrocytes as well as Müller cells incorporated bromodeoxyuridine after explantation. In noncrushed retinal explants Thy 1.1-immunopositive flat cells were much more frequent and the relative proportion of glial cells was much lower than in crush-activated cultures. In a second set of experiments the ability of adult rat retinal glia to support retinal ganglion cell regeneration was examined. Normal retinal explants (without optic nerve crush) which usually do not substantially regenerate axons were cultured on retinal glia from normal and crush-activated explants. Both glia preparations supported axon growth from retinal explants after 3 days in vitro. Neuritic growth was significantly better when retinal explants from normal adult rats were cultured on crush-activated retinal glia as compared to glia derived from noncrushed retinae. It is concluded that activated adult rat retinal glia, unlike adult glia found in other brain regions, support adult rat retinal ganglion cell regeneration in vitro.

Two patients with chronic alcohol abuse and central pontine myelinolysis are described. One developed a Korsakoff syndrome 2 days before admission to our hospital and the other showed signs of a incipient delirium without Korsakoff syndrome. Diagnosis of incipient central pontine myelinolysis was based on acute brain-stem dysfunction, serum electrolyte disturbances, malnutrition with vitamin B1 (thiamine), B6 (pyridoxine) and B12 (cyanocobalamin) deficiency in combination with typical neuroradiological findings. Hypokalaemia but no disturbance in serum sodium levels was found in both patients. After correction of hypokalaemia and vitamin deficiency the patients showed complete recovery of neurological and neuropsychological function. The findings are interpreted as suggesting that disturbances in serum potassium levels as well as rapid correction of hyponatraemia may be associated with pontine swelling and dysfunction which, if undetected, leads to central pontine myelinolysis.

The ability of lesioned adult retina ganglion cells (RGC) to survive and regrow axons in vitro was investigated in retina organ cultures under chemically defined conditions. Factors which are known to either affect the RGC survival like the basic fibroblast growth factor (FGF) or influence neurite outgrowth like gangliosides were assayed by recording the course of prelabeled RGC degeneration in vitro and the number and length of regrowing RGC axons from explanted retinal pieces. Administration of basic FGF significantly slowed down the decrease in the number of RITC-prelabeled RGC in the cultured retinae. In addition, in the presence of gangliosides (GM1, GD1a, GD1b GT1b), the numbers of regrown RGC axons (Thy 1-immunostained) increased dramatically as compared to controls. The data indicate that adult neurons with an intrinsic ability to regenerate axons can respond to substances with neurotrophic or neurite-promoting activities in tissue cultures.

The monoclonal antibody JONES recognizes a small group of gangliosides. Within the visual system of the adult rat JONES gangliosides are found only in those regions where neuronal regeneration is known to occur, i.e. the unmyelinated retina and optic nerve head. A transient increase in JONES ganglioside expression could be observed in the retinae of adult rats after optic nerve axotomy or in the retinae of animals receiving autologous sciatic nerve grafts. The highest levels of gangliosides identified by JONES were observed five days after surgery--contemporaneous with the maximum regenerative response of the adult rat retina after crush lesions. By double-labelling experiments using antibodies against glial cell markers--glial fibrillary acidic protein, S-100 and vimentin in conjunction with JONES-JONES gangliosides were shown to be expressed on retinal glial cells in vivo and in vitro. Elimination of glial cells by intraocular injection of aminoadipic acid abolished JONES labelling in vivo.

In order to compare a group of patients with a polymyositis (PM) to a control group, 28 cases of primary myopathies were examined by morphometry with regard to differences between central and peripheral muscle fibers in muscle fascicles. A significant difference in favor of peripheral muscle fibers, i.e., a peripheral hypertrophy was found in 22 out 28 cases (significantly in 14 cases). Therefore, histometry is a valuable additional method for discrimination between PM and primary myopathies.

A peripheral nerve exudate, collected in situ from the proximal end of a severed rat sciatic nerve, can induce substantial axonal elongation from ganglion cells when tested on explanted adult rat retinae. The responsive cells are identified on the basis of their Thy 1.1 immunostaining properties. Similar outgrowth can be obtained from explants when the culture medium is supplemented with brain-derived neurotrophic factor (BDNF). In addition, both BDNF and the sciatic nerve exudate can prevent ganglion cell degeneration as shown by the retrograde transport of a fluorescent dye that had been applied to the superior colliculus prior to explantation. The results demonstrate that soluble components, released by lesioned peripheral nerves, can effect adult retinal ganglion cells in a way that is reminiscent of that which has been described in vivo using sciatic nerve grafts after sectioning of the optic nerve. The molecular nature of these components is discussed.

Ambulatory blood pressure recordings and stress blood pressures during exercise were compared among hypertensive patients effectively treated with oxprenolol, nitrendipine, enalapril or low-dose clonidine. After 6 months of therapy, the means of blood pressure at rest and casual diastolic pressure were nearly identical among the four therapeutic groups. Although all pressures fell to within the normotensive range, casual systolic pressures were lower in patients treated with sympatholytic agents than in those taking enalapril. In contrast, average ambulatory blood pressure was less controlled in patients given clonidine or enalapril than in those given oxprenolol or nitrendipine. During physical stress patients taking clonidine showed the highest stress blood pressures and those taking oxprenolol the lowest pressures. The study demonstrated that although blood pressure was reduced to within the normotensive range in all four therapeutic groups, analysis of values of ambulatory blood pressure and stress blood pressure during physical activity showed a disparate pattern of antihypertensive efficacy.

Thirty-four cases of inflammatory muscle disease (21% from a collective of 160 inflammatory myopathies) were suitable for morphometric measurements. A statistical analysis of our data yields a perifascicular fiber atrophy (PA) in 50% of these cases. Morphometry was able to detect also cases with significant PA which were evaluated subjectively as normal. In dermatomyositis, the finding of a PA was more frequent than in other subgroups of inflammatory myopathies. There was also an accumulation of PA in patients with a paraneoplastic polymyositis. It could not be confirmed that PA occurs more frequent in dermatomyositis of children.

The potential for regeneration of adult rat ganglion cell (RGC) axons was investigated in vitro. Explants from RITC (rhodamine-B-isothiocyanate) retrogradely labeled and in vivo axotomized retinae were placed on dishes coated with various substrates. The retinal pieces were cultivated in a serum-free medium and incubated under 50 to 80% O2-enriched and 5% CO2-containing atmosphere. Under these conditions, massive outgrowth of fibers was observed as early as 24 h after explantation and over a period of time extending up to 7 days in culture. By various criteria, two main types of processes could be characterized: (1) Short, thick processes emerged from either migrated flat cells or from cells inside the retinal explant, and (2) long and thin processes emerged from cells in the ganglion cell layer (GCL). By immunohistochemistry, the short processes and the cells from which they had emerged, appeared to be glial acidic fibrillary protein (GFAP)-positive Thy 1 and L 1-negative, suggesting their glial nature. The second type of long, thin processes appeared to be GFAP-negative, L1- and Thy 1-positive, indicating that they were neuronal, probably RGC processes. Proof that long fibers emerged from RGCs was provided by retrograde labeling of RGCs with RITC prior to explanation. Numerous RITC-filled RGCs survived in vitro. Regrowing axons retransported part of the accumulated fluorescent dye in the orthograde direction and thus unequivocally permitted their identification as RGC axons. The fact that adult RGC axons can reelongate in vitro might provide a useful bioassay for investigations on the factors that either support or inhibit regrowth of axons from CNS neurons.

The impact of 4 antihypertensive drug regimens on blood pressure (BP) during everyday life stress and on BP during experimental stress in the laboratory was examined in an open clinical study. Sixty middle-aged men with mild-to-moderate essential hypertension never previously treated were treated either with low-dose clonidine (n = 10), oxprenolol (n = 20), nitrendipine (n = 20) or enalapril (n = 10). Before therapy, all 4 groups did not differ in age, weight, degree of obesity, BP at work site and casual BP measured in the outpatient clinic. After 6 months of effective therapy (casual BP within the normotensive range), casual diastolic BP was identical among the 4 groups, whereas systolic BP was lower in patients treated with clonidine or oxprenolol than in those who received enalapril. A disparate pattern of antihypertensive efficacy among the 4 groups emerged when stress BP was compared, with average ambulatory BP higher in patients receiving clonidine or enalapril than in those who had oxprenolol or nitrendipine. During ambulatory BP monitoring, patients treated with oxprenolol had the lowest level at each level of physical activity and self-reported emotional arousal. During bicycle exercise, patients receiving clonidine had the highest increase in systolic BP and those administered oxprenolol the lowest, whereas the BP response during mental stress was similar among all 4 therapeutic groups. The analysis of the hemodynamic response pattern during mental stress unmasked further disparities. Oxprenolol provoked an abnormal hemodynamic response during mental stress tests (increase in total peripheral resistance), whereas nitrendipine and enalapril preserved the physiological hemodynamic profile (decrease of total peripheral resistance).(ABSTRACT TRUNCATED AT 250 WORDS)