Evolution of adrenal regeneration hypertension in rats with actively regenerating or fully regenerated glands.
Explore the source record for details and available documents.
Adrenal Glands↗
SEARCH · Search PubMed
Results for “Regeneration”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
[Traditional and molecular biology approaches in the study of regeneration (based on materials from 3 international conferences). The 15th Singer Symposium on Regeneration (London, 20-21 March 1996), the 5th International Conference on the Development and Regeneration of the Extremities (University of York, 24-27 March 1996), the Conference of the British Society for Cell Biology and for Developmental Biology (University of York, 27-30 March 1996)].
Explore the source record for details and available documents.
Animals↗
Insulin receptors in Xenopus laevis liver and forelimb regenerates and the effects of local insulin deprivation on regeneration.
As forelimb regeneration in Xenopus laevis is mainly a cell proliferative event which results in a spike-shaped appendage, we set out to examine the possibility that insulin is a growth-promoting factor in this process. The objectives were 1) to detect the presence of insulin receptors (IRs) in the liver (a specific target organ for insulin) and IRs in the forelimb regenerates of X. laevis, 2) to determine whether the receptor is similar to IRs identified in other organisms, and 3) to absorb insulin locally by implanting anti-insulin antibody-soaked hydrolyzed polyacrylamide beads into regenerating forelimb outgrowths in order to assess the effects of insulin deprivation on regeneration. The results show that IRs are present in Xenopus liver plasma membranes (XLPM) as well as in plasma membranes of 21 day forelimb regenerates. Insulin binding to this receptor is time-dependent and specific, as unlabeled bovine insulin competes with radioiodinated insulin for binding to XLPM more effectively than insulin-like growth factor-I, guinea pig insulin, or glucagon. Scatchard analysis of insulin binding to XLPM describes a two binding site receptor possessing a low affinity (0.16 nM-1), high capacity (3.2 +/- 0.9 pM/mg) binding site and a high affinity (2.7 nM-1), low capacity (0.5 +/- 0.3 pM/mg) binding site. The holoreceptor has a molecular mass of 380 kDa. The reduced receptor has subunits of 130 kDa and 95 kDa. The 95 kDa subunit undergoes autophosphorylation following insulin stimulation. Implantation of hydrolyzed polyacrylamide beads, saturated with anti-insulin antibody, into regenerating Xenopus forelimbs significantly impeded development of the regenerates and, therefore, demonstrates that insulin is required for growth of Xenopus forelimb regenerates.
Affinity Labels↗
Prognostic factors for alveolar regeneration: effect of a space-providing biomaterial on guided tissue regeneration.
OBJECTIVES: There is a limited understanding of the effect of bone biomaterials on the healing potential when used in conjunction with guided tissue regeneration (GTR). The objective of this study was to evaluate the effect of a space-providing coral-derived biomaterial on alveolar bone regeneration in conjunction with GTR. METHODS: Bilateral, critical-size, 6-mm, supra-alveolar, periodontal defects were created in four young adult Beagle dogs. In a split-mouth design, the animals received an ePTFE device to provide for GTR in contralateral defect sites with or without the coral biomaterial. The animals were euthanized at 4 weeks post surgery. A histometric analysis assessed vertical regeneration of alveolar bone relative to space-provision by the ePTFE device. Because of the correlation of within-dog measurements, a mixed model ANOVA was used to analyze the data. RESULTS: There was significantly greater mean bone regeneration in sites receiving calcium carbonate coral implant GTR (cGTR) compared to GTR (p < 0.0001). Sites providing larger wound areas exhibited greater bone regeneration compared to sites exhibiting smaller wound areas (p < 0.0001). However, grouping the sites by wound area thresholds showed that bone regeneration was not significantly different in sites receiving cGTR compared to sites receiving GTR alone, irrespective of the size of the wound area (p > 0.5). CONCLUSIONS: Space-provision has a significant effect on bone regeneration following GTR. The coral biomaterial effectively enhances space-provision, and this appears to be the principal mechanism by which this biomaterial supports bone regeneration rather than postulated osteoconductive properties.
Absorbable Implants↗
Spontaneous regeneration of the corticospinal tract after transection in young rats: collagen type IV deposition and astrocytic scar in the lesion site are not the cause but the effect of failure of regeneration.
In young rats the corticospinal tract regenerated after a single transection of the spinal cord with a sharp blade, but regeneration failed if the transection was repeated to make a more traumatic injury. To identify cells and associated molecules that promote or impede regeneration, we compared expression of collagen type IV, glial fibrillary acidic protein (GFAP), and vimentin immunoreactivity (IR) at the lesion sites in combination with anterograde axonal tracing between animals with two types of transection. Axonal regeneration occurred as early as 18 hours after transection; regenerating axons penetrated vessel-like structures with collagen type IV-IR at the lesion site, while reactive astrocytes coexpressing GFAP- and vimentin-IR appeared in the lesioned white matter. In contrast, when regeneration failed astrocytes were absent near the lesion. By 7 days sheet-like structures with collagen type IV-IR and astrocytic scar appeared in the lesioned white matter and persisted until the end of the observation period (31 days). On the basis of their spatiotemporal appearance, collagen type IV-IR sheet-like structures and the astrocytic scar follow, rather than cause, the failure of regeneration. The major sign, and perhaps cause, of failure of axonal regeneration is likely the prolonged disappearance of astrocytes around the lesion site in the early postinjury period.
Animals↗
Implantation of MNNG crystals into a Triturus intact limb affects mitotic and labeling indices, regeneration rate, and morphogenesis in the contralateral, regenerating limb.
Experimental administration of chemical carcinogens to various mammals is highly effective in inducing malignant tumors. In contrast, treatment of regeneration-competent animals even with much higher doses of the same drugs only exceptionally leads to tumor-like growth. Usually, carcinogenic materials implanted or injected into a regenerating limb of urodele amphibia interfere with the regenerative process and frequently lead a). to growth retardation or arrest of regeneration, b). to development of a great variety of abnormal regenerates, and c). to generation of accessory, limb-like structures. Autonomous or experimental incidence of carcinogenesis is extremely low in animals endowed with strong regenerative capabilities. Of exceptional biological significance is the fact that such induced tumors usually regress spontaneously. This unique property of the regeneration-competent animals to resist carcinogenesis provides opportunities to compare non-cancerous alterations in the differentiated state of adult cells to those occurring in neoplasia. The mode of action of the chemical carcinogens on limb regeneration has not yet been clarified with certainty at the cellular and the molecular level. Several scientists claim that the above-mentioned effects might be attributed to local toxic influences of the drugs; therefore the present study was designed to investigate whether the administration of the carcinogen MNNG can affect cell proliferation, histogenesis, and morphogenesis at a region distant from the site of its implantation, even after a relatively long time period. To this end, 40 animals of the species Triturus cristatus had their right hindlimb surgically removed at the distal zeugopod. Then, a small microcrystal (approximately 5 micro g) of MNNG was inserted under the ventral aspect of the skin of the left tarsus in 20 of these animals (groups T and A; see below). Two months later, nine of the MNNG-treated animals were injected intraperitoneally with tritiated thymidine. After 2 h, six of these animals had their right hindlimb amputated at the distal zeugopod, whereas the rest were left to regenerate. The results were evaluated by camera lucida drawings, clearing in methyl benzoate, classical histology, and autoradiography. It was revealed that administration of MNNG at a somatic region (left hindlimb) reduces DNA synthesis and mitosis at a distant place (right hindlimb) even 2 months after MNNG implantation. Despite this, the rate of limb elongation is not substantially reduced. Classical histology revealed normal tissue structure throughout. All regenerated limbs displayed several teratogenic abnormalities.
Amputation, Surgical↗
Regeneration in Salaria pavo (Blenniidae, Teleostei). Histogenesis of the regenerating pectoral fin suggests different mechanisms for morphogenesis and structural maintenance.
The pectoral fin of blennies is differentiated into a dorsal field and a ventral hook field. A histogenetic analysis of the regenerating pectoral fin was related to two questions. First, are histological specializations of the hook field responsible for the impairment of the regenerative capacity of pectoral fins of blennies? Second, can analysis of the temporal sequence of histogenetic events be used to make testable predictions about the tissue interactions required to re-establish the adult pattern? Regeneration of pectoral fins was examined in Salaria pavo (Blenniidae, Teleostei). Approximately 80% of the length of the fin rays was amputated. Fin ray stumps were evaluated 7, 14, 24, 48 and 72 h after amputation, regenerates 4, 5, and 6 days after amputation and at length of about 30%, 50% and 60% regeneration of the original fin length. The regeneration process is subdivided into four stages: wound healing, blastema formation, fin ray formation and distal outgrowth and differentiation of hook characters. Analysis of the early events of regeneration, wound healing, blastema formation and distal outgrowth, yielded no profound differences from those of conventional fins in general. Impairment of regenerative capacity becomes manifested before histological differentiation of hook characters, and it is thus unlikely that their presence is the proximate cause of heteromorphic regeneration. The sequence in which the anatomical specializations characteristic of fin hooks (lepidotrichal cord, cuticle, fin web regression) appear was variable. Detailed analysis of older regenerates revealed a more regular pattern. In the first phase the characters appear to be largely independently organized, while they become locally correlated later. It is concluded that the anatomical differentiation passes through two stages, initiation of anatomical differentiation, and then mutual adjustment of character expression leading to spatially correlated expression of the lepidotrichal cord, the cuticle and the fin web regression.
Animals↗
Nerve regeneration across a 25-mm gap bridged by a polyglycolic acid-collagen tube: a histological and electrophysiological evaluation of regenerated nerves.
In the study reported here we have examined the nerve regeneration that occurs over a 25-mm gap using a novel biodegradable nerve guide tube. The tube was a composite of polyglycolic acid (PGA) mesh coated with collagen which was filled with neurotrophic factors. The left sciatic nerve of ten adult cats was dissected. The stumps were connected by the tube, and fixed gap. Histological examinations carried out 4-16 months after implantation of the tube revealed regeneration of well vascularized nerve tissue. Regeneration of both myelinated, unmyelinated axons and Schwann cells was confirmed by electron microscopy 5 months after surgery. Following injection of horseradish peroxidase (HRP) into a site peripheral to the regenerated segment of the sciatic nerves, motoneurons in the ventral horn of the spinal cord, afferent terminals in the medial portion of the dorsal column of the medulla oblongata, and sensory afferent nerve terminals in the dorsal horn of the spinal cord were labelled. Electrophysiological examinations revealed restoration of evoked electromyograms and sensory evoked potentials (SEPs) recorded from the cerebral cortex as well as the spinal cord. We also found that some of the regenerated motor axons exhibited branching in the regenerated segments. In two cases, a single motoneuronal axon from the regenerated side projected to both flexors and extensors, simultaneously. Our results indicate that the PGA-collagen composite tube is a promising tool for use as a nerve guide tube in peripheral nerve regeneration.
Animals↗
Molecular cloning of up-regulated cytoskeletal genes from regenerating skeletal muscle: potential role of myocyte enhancer factor 2 proteins in the activation of muscle-regeneration-associated genes.
A subtractive hybridization and cloning strategy was used to identify genes that are up-regulated in regenerating compared with normal skeletal muscle. The gastrocnemius muscle of CD1 mice was injected with a myotoxic agent (BaCl2). A cDNA library was constructed from the regenerating muscle, and was screened with subtracted probes enriched in genes up-regulated during regeneration. Cofilin and vimentin cDNA clones were isolated. Both cofilin and vimentin were demonstrated to be overexpressed in regenerating compared with non-regenerating muscle (17-fold and 19-fold induction respectively). Cofilin and vimentin mRNAs also exhibited an increased expression in C2C12 myoblasts and a decreased expression in differentiated myotubes. Analysis of the regeneration-induced vimentin enhancer/promoter region revealed a consensus binding site for the myocyte enhancer factor 2 (MEF2) transcription factors. Electrophoretic mobility-shift assays and in vivo reporter assays revealed that MEF2 DNA-binding activity and transcriptional activation are increased in regenerating skeletal muscle, indicating that they may play a role in the activation of muscle genes during regeneration. These data suggest that both cofilin (an actin-regulatory protein) and vimentin (an intermediate filament) may be key components of the cytoskeletal reorganization that mediates muscle cell development and adult skeletal-muscle repair.
Actin Depolymerizing Factors↗
Disto-proximal regional determination and intercalary regeneration in planarians, revealed by retinoic acid induced disruption of regeneration.
The mechanisms that define the body pattern during development and regeneration are the object of major concern in developmental biology. To understand the process and sequence of antero-posterior pattern formation of planarian body regions during regeneration, regenerating organisms were treated with exogenous retinoic acid, which affects development and regeneration in other systems, and the sequence of regional determination has been monitored by a specific molecular marker for the central region, which includes the pharynx. The sequence of gross regional specification have never been analysed in planarians using molecular regional markers or by direct disruption of the regeneration process. Exogenous retinoic acid administration on regenerating planarians disrupts anterior, but not posterior regeneration. The period of maximum sensitivity to exogenous retinoic acid is one day after amputation, during which time the determination of the head has been reported to occur. The data obtained allow us to suggest that gross regional specification during planarian regeneration is disto-proximal, from the regenerative blastema to the old stump, and thus takes place by intercalation of the central region between the anterior and posterior ones.
Animals↗
Nerve regeneration in cornea after penetrating keratoplasty in rabbit, with special reference to relationship between regenerating nerves and basal laminae.
The pattern of nerve regeneration in the grafted rabbit cornea was investigated by electron microscopy. Grafted corneas were excised 2, 7, 14 and 28 days after grafting, and processed for observation by conventional electron microscopy. In the normal, unoperated cornea Schwann cell basal laminae are, unlike those of ordinary peripheral nerves, discontinuous and fragmentary on the fibers coursing through the corneal stroma. In the early stage of regeneration, while numbers of regenerating axons extended through the Schwann cell columns of regenerating axons extended through the Schwann cell columns in the grafts, many other regenerating axons elongated as single fibers through the corneal stroma outside the Schwann cell columns. These single naked axons were later enveloped by Schwann cell cytoplasm, contributing to the overall dense irregular pattern of regenerated nerves in the grafted cornea. It was thought that the regenerating axons can extend throughout the stroma without the guidance of basal lamina tubes, making the corneal stroma a favorable environment for nerve regeneration.
Animals↗
Effect of intracellular pH and two growth factors, epidermal growth factor and human hepatocyte growth factor, on DNA synthesis in non-regenerating and regenerating hepatocytes and hepatoma cells.
I examined the effects of intracellular pH (pHi) and the growth factors, epidermal growth factor (EGF) and human hepatocyte growth factor (HGF), on DNA synthesis in non-regenerating hepatocytes, regenerating hepatocytes and hepatoma cells. Non-regenerating and regenerating hepatocytes were isolated from the livers of intact adult rat and of the adult rat 24 hours after 70% hepatectomy, respectively. Hep G2 cells, a human hepatoma cell line, was employed as hepatoma cells. Regenerating hepatocytes and Hep G2 cells, but not non-regenerating hepatocytes displayed increased DNA synthesis with increasing pHi in the absence of EGF and HGF. However, non-regenerating hepatocytes displayed little increase, regenerating hepatocytes displayed substantial increase in DNA synthesis with increasing pHi in the presence of EGF or HGF. In contrast, Hep G2 cells displayed decreased DNA synthesis in the presence of HGF but not EGF. These findings indicate that pHi influences the fashion of proliferation in hepatocytes and cancer cells. EGF and HGF stimulate DNA synthesis in hepatocyte and inhibit that in cancer cell, suggesting that increasing pHi and administration of these growth factors may be one of the effective treatment for hepatoma.
Animals↗
Early regeneration genes: Building a molecular profile for shared expression in cornea-lens transdifferentiation and hindlimb regeneration in Xenopus laevis.
Recent studies in Xenopus laevis have begun to compare gene expression during regeneration with that of the original development of specific structures (e.g., the hindlimb and lens), while other studies have sought differences in gene expression between regeneration-competent and regeneration-incompetent stages. To determine whether there are any similarities between the regeneration of different structures, we have used a differential screen to seek shared early gene expression between hindlimb regeneration and cornea-lens transdifferentiation in the Xenopus tadpole. We have isolated 13 clones representing genes whose expression is up-regulated within the first few days of both regenerating processes and which are not demonstrably up-regulated in the context of basic wound healing. Furthermore, all of these genes also show prominent late embryonic expression. The expression patterns and putative identities of all 13 genes are presented, and a model is considered that allows us to characterize and profile important changes in gene expression, which might be shared among various regenerating and developmental systems.
Animals↗
Activity-driven sharpening of the regenerating retinotectal projection: effects of blocking or synchronizing activity on the morphology of individual regenerating arbors.
Both blocking activity with intraocular tetrodotoxin (TTX) and synchronizing activity with a xenon strobe light (1 Hz) prevent retinotopic sharpening of regenerating optic projection in goldfish (Meyer, 1983; Schmidt, 1985; Cook and Rankin, 1986). In this study, we tested, in both normal and regenerating projections, the effects of these two treatments on individual optic arbors. Arbors were stained via anterograde transport of HRP, drawn in camera lucida from tectal whole mounts, and analyzed for spatial extent in the plane of the retinotopic map, order of branching, number of branch endings, depth of termination, and the caliber of the parent axon. In normal tectum, fine, medium, and coarse caliber axons gave rise to small, medium, and large arbors, which averaged 127 microns, 211 microns and 275 microns in horizontal extent, and terminated at characteristic depths. All three classes averaged roughly 21 branch endings. Optic arbors that regenerated with normal patterns of activity returned to a roughly normal appearance by 6-11 weeks postcrush: the same three calibers of axons gave rise to the same three sizes of arbors at the same depths, but they were much less stratified and well on average about 16% larger in horizontal extent. At this time point, arbors regenerated under TTX or strobe were on the average 71 and 119% larger, respectively, than the control-regenerated arbors (larger in all classes), although they had approximately the same number of branch endings and were equally poorly stratified. Synapses formed under strobe were also normal in appearance. Thus the only significant effect of both strobe and TTX treatment was to enlarge the spatial extent of arbor branches. Arbors that were not regenerating were very slightly (but significantly) enlarged by TTX block of activity or strobe illumination. As previous staining showed that regenerating axons initially make widespread branches and later retract many of those branches (Schmidt, Turcotte, Buzzard, and Tieman, 1988; Stuermer, 1988), the present findings support the idea that blocking activity or synchronizing activity prevents retinotopic sharpening by interfering with the elimination of some of the errant branches.
Animals↗
Regeneration of sciatic nerve in frogs maintained at 15 degrees C: failure to sustain regeneration after initiation.
Peripheral nerve regeneration proceeds through a series of phases which include axonal sprouting, elongation, and maturation. Each phase requires interaction between intrinsic properties of the injured neuron and nonneural elements in the environment into which the nerve grows. It has been difficult, however, to separate processes which depend on the induction of a cell body response from those which may depend on local factors at the site of injury. Recently, we found that frog peripheral nerves, in animals housed at 15 degrees C, were able to initiate regeneration in the absence of an apparent cell body response. Subsequently, we found that these nerves did not continue to regenerate normally. I investigated the ultrastructure of regenerating nerves from frogs kept at 15 degrees C for 92 days after a freeze-lesion. Injured sciatic nerves showed extensive axonal sprouting at the lesion site but little continued growth distal to the injury, indicating an impairment in elongation and maturation. Nonneural cells in the local environment showed extensive distributions of rough endoplasmic reticulum and free ribosomes near the regenerative sprouts but the type and quantity of protein actually being synthesized was not determined. The basis for the suppression of axonal growth remains unknown but in the absence of an apparent cell body response it appears probable that a necessary cell body contribution to regeneration was also absent. That contribution could provide direct support to axonal growth or could trigger periaxonal support of regeneration. This experimental preparation offers a means of investigating those alternatives and the opportunity to determine the origin of the various processes responsible for nerve regeneration.
Animals↗
Regeneration of lesioned cholinergic septal neurons of the adult rat can be promoted by peripheral nerve grafts and a fibrin-fibronectin-containing matrix of peripheral regeneration chambers.
Axonal regeneration of septal cholinergic neurons was examined after lesion of the septohippocampal pathway of the adult rat and implantation of tubes containing peripheral cellular or acellular substrates. After empty tube implantation, no regenerated structures were observed in the conduit. However, after implanting tubes filled with sections of predegenerated sciatic nerves or a fibrin-fibronectin-containing matrix provided by peripheral regeneration chambers, numerous regenerated axons were detected 6 weeks after the operation. At the electron microscopic level, regenerated axons were observed in the grafted sciatic nerves in contact with Schwann cells but also in contact with astrocytes which were able to migrate and send processes into the graft. After fibrin-fibronectin-containing-matrix implantation, the regenerated structure between septum and hippocampus was composed mainly of fibroblasts, astrocytes, and regenerated axons associated to these central glial cells.
Acetylcholine↗
Spontaneous regeneration of the corticospinal tract after transection in young rats: a key role of reactive astrocytes in making favorable and unfavorable conditions for regeneration.
We demonstrated the occurrence of marked regeneration of the corticospinal tract (CST) after a single transection and failure of regeneration after a repeated transection in young rats. To provide convincing evidence for the complete transection and regeneration we used retrograde neuronal double labeling. Double-labeled neurons that took up the first tracer from the transection site and the second tracer from the injection site caudal to the transection site were observed in the sensorimotor cortex. The anterograde tracing method revealed various patterns of regeneration. In the most successful cases the vast majority of regenerated fibers descended in the normal tract and terminated normally whereas a trace amount of fibers coursed aberrantly. In the less successful cases fibers descended partly normally and partly aberrantly or totally aberrantly. To clarify the role of astrocytes in determining the success or failure of regeneration we compared expression of glial fibrillary acidic protein (GFAP), vimentin and neurofilament (NF) immunoreactivity (IR) in the lesion between single and repeated transections. In either transection, astrocytes disappeared from the CST near the lesion site as early as 3 h after lesioning. However, by 24 h after a single transection, immature astrocytes coexpressing GFAP- and vimentin-IR appeared in the former astrocyte-free area and NF-positive axons crossed the lesion. By contrast, after a repeated transection the astrocyte-free area spread and NF-positive axons never crossed the lesion. It appears likely that the major sign, and possibly cause of failure of regeneration is the prolonged disappearance of astrocytes in the lesioned tract area.
Animals↗
Putative gap junctional communication between axon and regenerating Schwann cells during mammalian peripheral nerve regeneration.
Gap junctions are intercellular channels which mediate the traffic of ions and a variety of molecular messengers between contiguous cells. Here, we report on the possibility that atypical gap junctions develop between heterologous tissues, such as regenerating nerve axons and Schwann cells, during peripheral nerve regeneration in adult rats. After a complete transection and subsequent regeneration in the rat sciatic nerve distal segment, a small scale gap junction-like structure was observed between the regenerating axons and adjoining Schwann cells. Immunoelectron microscopy showed that one of the gap junctional proteins, connexin32, was located at a small region of contact between the axon and Schwann cells. Biocytin, a small molecular weight dye, was transported from regenerating axons into adjoining Schwann cells. The present findings suggest that regenerating axons communicate directly with adjacent Schwann cells through small gap junctions, which may play a role in the mechanism of regeneration following nerve transection.
Animals↗