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Pattern of bromodeoxyuridine incorporation in the advanced stages of arm regeneration in the feather star Antedon mediterranea.

The overall process of arm regeneration in the crinoid Antedon mediterranea is a typical epimorphic process (blastemal regeneration). This can be subdivided into three main phases: a repair phase, an early regenerative phase, and an advanced regenerative phase. The crucial problem of the identification of cell lineages responsible for both repair and regenerative processes has been approached by monitoring cell proliferation during the advanced regenerative phase using light-microscopic and ultrastructural immunocytochemical methods to detect the incorporation of the thymidine analogue bromodeoxyuridine (BrdU) into regenerating tissues. Various treatment protocols and BrdU incubation times have been employed and provided information not only on the sources, sites of proliferation, and recruitment times of the new cells, but also on the cell lineage involved and subsequent fate (differentiation and/or migration) of the labelled cells. Our results are consistent with the following conclusions: (1) The arm regeneration process is due to a massive intervention of active proliferating cells identifiable as migratory, morphologically undifferentiated cells (amoebocytes and coelomocytes). (2) The preferential proliferation sites of these cells are the terminal blastema, the coelomic epithelium, and the brachial nerve of both the regenerating arm and the stump, even far from the amputation. (3) The two main cell components contributing to the regenerate have different origins: the blastemal cells and all the cell lineages derived from the amoebocytes; the coelomic cells from the migratory coelomocytes, in their turn derived from proliferation of the coelomic epithelium. (4) The blastemal regeneration of Antedon is due to a combined recruitment of pluripotent elements, implying the intervention of presumptive stem cells (amoebocytes) and the transdifferentiation/dedifferentiation of differentiated elements of the coelomic epithelium.

Animals↗

Present situation and future aspects of spinal cord regeneration.

The central nervous system (CNS) has a limited capacity for regeneration after injury. In spinal cord injury (SCI) patients, total loss of all motor and sensory function occurs below the level of injury. Advances in treatment are expected for orthopedic and spinal surgeons. Recently, evidence of axonal regeneration and functional recovery has been reported in animal spinal cord injury models. Our studies on the roles of inhibitory molecules with a comparison between neonatal and adult animals may help serve as therapeutic targets to enhance axonal regeneration for the injured spinal cord. Also, our cell replacement study indicates the possibility of transplanting neural stem cells to supply the cell source for immature oligodendrocytes, which are thought to be essential for both the myelination and trophic support of regenerating axons in the spinal cord. Administration of neurotrophic factors, prevention of inhibitory factors, and stem cell technology have clinical applications in SCI patients. However, spinal cord regeneration involves a multistep process, and several factors have to be controlled after injury. A combination of several treatments could overcome a nonpermissive environment for spinal cord regeneration. Further understanding of the mechanisms and finding optimal targets of spinal cord regeneration are necessary to obtain successful therapies for SCI patients.

Animals↗

[Evaluation of potential damage to the regenerate during callus molding after mandibular distraction osteogenesis. Experimental study using an animal model].

BACKGROUND: Molding the regenerate created by distraction osteogenesis has clinically been shown to be an efficient lifeboat, good enough that for complex three-dimensional deformities final adjustments by molding the regenerate may be part of the treatment plan. The study assessed the limits of molding a regenerate, taking into consideration compressive and tensile forces acting simultaneously on the fresh callus. MATERIAL AND METHODS: Distraction osteogenesis was performed in 15 beagle mandibles using custom-made devices which allowed for lengthening as well as for angulation. After linear distraction of 10 mm, a defined 20 degrees angulation was performed in one acute step. The position of the fulcrum of the device allowed the regenerate to be compressed and stretched simultaneously. The effects on bone healing were assessed after 6 or 13 weeks of consolidation and compared to a control group where only linear distraction was performed. RESULTS: Radiological and histological investigations demonstrated that no significant difference between the biological behavior of the compressed and the stretched zone of the regenerate could be found. However, there were signs, showing the more critical character of the stretched area. After 6 weeks of consolidation, some specimens revealed delayed ossification of the stretched zone. Under stable conditions, this delay was compensated after 13 weeks of consolidation and complete osseous healing occurred. CONCLUSIONS: Under stable conditions, a fresh regenerate can be molded to a considerable extent without endangering osseous healing permanently. Nevertheless, tensile forces acting on the regenerate should be minimized to prevent damage to the new bone. This can be achieved by overdistraction prior to callus molding or by gradually changing the vector of distraction during the lengthening process.

Animals↗

Biological behavior of myoepithelial cells in the regeneration of rat atrophied sublingual glands following release from duct ligation.

The present study aimed to clarify how myoepithelial cells behave during regeneration of an atrophied sublingual gland by investigating cell proliferation and ultrastructure. Atrophy of rat sublingual glands was induced by unilateral ligation of the excretory duct near the hilum with metal clips, which were then removed after one week of ligation for regeneration. The sublingual glands 0-14 days after unligation were examined with single immunohistochemistry for actin as a marker of myoepithelial cells, double immunohistochemistry for actin and proliferating cell nuclear antigen (PCNA) as a marker of proliferating cells, and transmission electron microscopy (TEM). The single immunohistochemistry and TEM showed that myoepithelial cells surrounded residual ducts in the atrophied glands and immature and mature acini in the regenerating glands. Although PCNA-positive myoepithelial cells were identified during regeneration, PCNA labeling indices of myoepithelial cells were low at all time points except at day 7. Ultrastructurally, myoepithelial cells showing bizarre shaped structures in the atrophy changed with maturation of differentiating acinar cells and appeared normal in the regenerated glands. There was no differentiation of the remaining duct cells to myoepithelial cells. These observations suggest that proliferation of myoepithelial cells and differentiation to myoepithelial cells do not commonly participate in the regeneration of atrophied sublingual glands and that the bizarre shaped myoepithelial cells in the atrophied sublingual glands recover the original shapes with acinar cell regeneration.

Actins↗

Regeneration of normal terminal innervation patterns by central noradrenergic neurons after 5,7-dihydroxytryptamine-induced axotomy in the adult rat.

The regeneration of central adrenergic axons has been followed between 5 days and 18 months after 5,7-dihydroxytryptamine(5,7-DHT)-induced axotomy in the adult rat, using fluorescence histochemistry in combination with noradrenaline (NA) determinations and [3H]NA uptake measurements. The axonal and terminal degeneration caused by the 5,7-DHT treatment (150 micrograms intraventricularly) was, by 1--2 weeks after injection, accompanied by a 70% reduction of NA in the forebrain and 30% reduction in the brain stem, and by 43--85% reductions in the [3H]NA uptake capacity in various regions of the brain and spinal cord. Signs of sprouting of the drug-lesioned axons were evident along the terminal axon segments at 5 days after treatment. The sprouts increased rapidly in length and number during the subsequent weeks and by 2--6 months after injection new NA terminal systems of relatively normal density and distribution had been re-established in many initially denervated regions. In parallel there was a recovery of endogenous NA and [3H]NA uptake to the pre-injection levels in the brain, and to levels 50--75% of normal in the cervical and thoracic spinal cord. Four successive phases of the regeneration process are distinguished: (1) primary sprouting from the lesioned NA axon stumps, occurring within the first week after treatment; (2) seemingly random growth and proliferation of the newly formed sprouts during the second and third weeks; (3) directed, forward growth of some of the sprouts leading to a partial restoration of the original fibre paths, branching patterns and terminal networks within 3--6 months; (4) a concomitant removal of at least part of the abnormally directed sprouts. Although the original fibre architecture was quite accurately restored in many areas the regeneration was not always correct. Hyperinnervation patterns and abnormal terminal arrangements were often formed, and in the spinal cord the down-growth of the regenerating axons occurred predominantly along a route that is inconspicuous in the normal rat. It is concluded that at least certain types of central neurons regenerate very efficiently provided the conditions are favourable, and that under such conditions axonal regeneration in the mammalian CNS is subjected to regulatory mechanisms that can be very precise. The results provide evidence that the adult mammalian CNS possesses mechanisms for axonal guidance which allow the accurate regeneration of lesioned axonal tracts and branching patterns, as well as mechanisms of recognition making possible the re-establishment of the original terminal connections.

5,7-Dihydroxytryptamine↗

An anatomical and physiological study of regeneration of the eighth nerve in the leopard frog.

The ability of auditory fibers in the anuran's VIIIth nerve to regenerate back into the central nervous system after their axons have been served was studied electrophysiologically and anatomically. Single unit recordings in the regenerated portion of the nerve indicate that: (1) fibers from both the amphibian and basilar papillae regenerate; (2) tuning curves of regenerated fibers, as in normal fibers, are 'V' shaped and retain their sharp frequency selectivity; (3) latency and threshold measurements of regenerated fibers are similar to values obtained in intact nerves. Filling the posterior branch of the regenerated VIIIth nerve with horseradish peroxidase indicates that fibers in this branch remain together within the nerve during regeneration and succeed in terminating in their correct target nuclei and no others.

Animals↗

Perikaryal routing of newly synthesized proteins in regenerating neurons: quantitative electron microscopic autoradiography.

Intracellular transport of newly synthesized proteins through organelles in the perikarya of regenerating goldfish retinal ganglion cells was studied using electron microscopic autoradiography. Retinas were removed 14 or 30 days after optic tract cut or sham operation, pulse-labeled in [3H]proline-containing medium for 5 min, and then chase-incubated in medium containing unlabeled proline for various times up to 55 min before fixation. Fourteen days after axotomy, during rapid growth of the regenerating axons, the time course of change of relative grain density (% grains/% area) in the rough endoplasmic reticulum in regenerating cells was almost identical to that in control cells. However, the grain distribution analysis revealed an increased delivery of newly synthesized proteins to the Golgi apparatus, perikaryal plasma membrane and nucleus in regenerating cells. Thirty days after axotomy, during synaptogenesis, Golgi apparatus labeling in the regenerating cells became significantly higher than control, but the increase was delayed compared to the increase seen 14 days after axotomy. Labeling of the plasma membrane and nucleus did not rise above control in 30-day regenerating cells chase-incubated for up to 55 min. Thus the pattern of intracellular transport of newly synthesized proteins varies with the stage stage of axonal regeneration.

Animals↗

Regenerating nerve fibres do not displace the collateral reinnervation of cat teeth.

Experiments in adult cats have shown that when the inferior alveolar nerve is sectioned and regeneration blocked, there is extensive collateral reinnervation from neighbouring nerves which reinnervate the denervated teeth. In the present experiments the fate of collateral nerve fibres supplying the teeth has been investigated following regeneration of the inferior alveolar nerve. In some experiments the inferior alveolar nerve was sectioned and regeneration temporarily blocked whilst in others the nerve was frozen but not sectioned, to allow a more complete restoration of normal properties after regeneration. The jaw opening reflex evoked by electrical stimulation of the left canine and incisor teeth was abolished by left inferior alveolar nerve section or freeze but returned within 3-9 weeks due to reinnervation by collateral nerve fibres. Regenerating inferior alveolar nerve fibres were allowed to reinnervate the teeth 12-15 weeks after the initial nerve injury. Twenty seven weeks after the initial nerve injury, pulpal nerve fibres supplying the teeth which had been denervated were present in the regenerated inferior alveolar nerve as well as the ipsilateral lingual and mylohyoid nerves and the contralateral inferior alveolar, lingual and mylohyoid nerves. Except for the ipsilateral inferior alveolar and lingual nerves, these nerves do not normally include pulpal fibres from these teeth. In these experiments, therefore, after inferior alveolar nerve section or freeze, the collateral reinnervation of tooth pulps was not withdrawn following the return of regenerating nerve fibres.

Animals↗

Neurite-promoting factors and extracellular matrix components accumulating in vivo within nerve regeneration chambers.

The outgrowth of neurites from cultured neurons can be induced by the extracellular matrix glycoproteins, fibronectin and laminin, and by polyornithine-binding neurite-promoting factors (NPFs) derived from culture media conditioned by Schwann, or other cultured cells. We have examined the occurrence of fibronectin, laminin and NPFs during peripheral nerve regeneration in vivo. A previously established model of peripheral nerve regeneration was used in which a transected rat sciatic nerve regenerates through a silicone chamber bridging a 10 mm interstump gap. The distribution of fibronectin and laminin during regeneration was assessed by indirect immunofluorescence. Seven days after nerve transection the regenerating structure within the chamber consisted primarily of a fibrous matrix which stained with anti-fibronectin but not anti-laminin. At 14 days, cellular outgrowths from the proximal and distal stumps (along which neurites grow) had entered the fibronectin-containing matrix, consistent with a role of fibronectin in promoting cell migration. Within these outgrowths non-vascular as well as vascular cells stained with anti-fibronectin and anti-laminin. Within the degenerated distal nerve segment, cell characteristic of Bungner bands (rows of Schwann cells along which regenerating neurites extend) stained with anti-fibronectin and laminin. The fluid surrounding the regenerating nerve was found to contain NPF activity for cultured ciliary ganglia neurons which markedly increased during the period of neurite growth into the chamber. In previous studies using this particular neurite-promoting assay, laminin but to a much lesser extent fibronectin also promoted neurite outgrowth.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Properties of cutaneous mechanosensitive afferents during the early stages of regeneration in man.

The technique of percutaneous microneurography was used to record single unit activity from 75 regenerated primary afferents innervating the glabrous skin of the human hand. Thirteen patients were studied, who had suffered complete transection, with subsequent suture or graft, of the median or ulnar nerves. The recordings were obtained from 7 to 23 months postoperatively (early regeneration). Three types of mechanoreceptive afferents (RA, SAI, SAII) and many deep units of unknown origin were found. No regenerated PC units could be identified. The reinnervated receptors were predominantly located in the palm and proximal fingers, comparable to those found 3 years or more postoperatively (late regeneration). Response thresholds and in general, discharge and receptive field characteristics of the majority of afferents were largely comparable to late regeneration and normal. The properties of SAII units were like normal in all respects. However, several distinct abnormalities were encountered early during regeneration: multiple receptive fields innervated by a single afferent (2/9 RA and 2/9 SAI), unusually small or large receptive fields (RA and SAI), pronounced fatigue on repetitive stimulation (7/15 SAI, 4/6 deep). Responses of reinnervated skin to sustained and repeated indentations were found to be similar to those of normal skin, and therefore, could not account for the abnormal discharge behavior. It is suggested that the transitional properties of regenerating afferents reflect unstable axon-end organ connections and immature axonal properties. Both factors would contribute to the slow course of sensory recovery, making prognosis on tactile recovery unpredictable.

Adolescent↗

Myelin sheath remodelling in regenerated rat sciatic nerve.

Adult rat sciatic nerves were subjected to a crush lesion and allowed to survive during 2 weeks-11 months. Segments of regenerated nerve were removed from exsanguinated animals and subjected to physiological analysis and light microscopic examination of teased fibres. Application of the potassium channel blocking agent 4-aminopyridine (4-AP) to regenerated nerve segments had marked effects on action potential waveform and recovery properties. When applied to normal control nerves 4-AP had minimal effects. Examination of teased preparations from the same nerves revealed the presence of two classes of internodes along regenerated nerve fibres. A majority of conventional regenerated internodes exhibited lengths (L) of at least 150 microns. Maximal L reached about 350 microns after one month survival and 550 microns 10 months later. In the individual nerve the maximal L-values tended to increase with fibre size. Most convential regenerated internodes had L-values of 200-400 microns. In addition, scattered unusually short sheaths, with L-values of 10-150 microns, were found intercalated between conventional internodes. Some intercalated sheaths had a wrinkled irregular configuration and some lacked a light-microscopically distinct myelin layer. We suggest that the occurrence of unusually short and partly distorted sheaths along regenerated fibres reflects a nodal-internodal remodelling in response to longitudinal crowding. These sites might represent foci with aberrant functional properties, possibly accounting for the 4-AP sensitivity of regenerated nerve.

4-Aminopyridine↗

Basal laminae and Meissner corpuscle regeneration.

Murine Meissner corpuscles (mouse digital corpuscles), located in pad skin at the toe tip, consist of lamellar cells with long cellular processes (lamellae) surrounding axon terminals in an onion-skin fashion. Lamellar cell bodies and processes were provided with a basal lamina. The present study was made to examine whether these lamellar cell basal laminae have any specific role in the differentiation of regenerating axons and Schwann cells into specialized axon terminals and lamellar cells, respectively. Pad skin at the toe tip was treated 3-5 X by freezing and thawing. By this treatment, cellular constituents of the corpuscles die and disintegrate into cell debris, leaving in situ basal laminae of the lamellar cells in stacked hollow loops, reminiscent of the original configuration of lamellae. Schwann cells and axons of the ordinary nerve fibers in the pad skin were similarly damaged, and basal laminae of the Schwann cells remained as basal lamina tubes. Three days after treatment, regenerating axons were seen extending through the basal lamina tubes of Schwann cells deep in the toe pad skin. However, no regenerating axons were found in the vicinity of the old corpuscles. Five days after treatment, regenerating axons, some of which were accompanied by migrating Schwann cells and others which were still naked, were noted at the subepidermal region, and began to enter the hollow basal lamina loops of the old corpuscles. Eight-15 days after treatment, regenerating axons which entered the basal lamina loops successively gave rise to branches, and at the same time, accompanying Schwann cells emanated cellular processes through well-preserved basal lamina loops. Fifteen-25 days after treatment, regenerating axons seemed to be morphologically specialized as axon terminals, and accompanying Schwann cells differentiated into definite lamellar cells which surrounded the axon terminals in the same manner as in the normal murine Meissner corpuscles. Although the incidence of good regeneration of the corpuscle was relatively low, these findings suggested that basal laminae of lamellar cells might have some specific properties which could be responsible for the differentiation as well as maintenance of lamellar cells and axon terminals in the Meissner corpuscles.

Animals↗

The formation of a 'pseudo-nerve' in silicone chambers in the absence of regenerating axons.

The formation of a regenerate between sciatic nerve segments or stumps inserted into Y-tunnelled silicone chambers was studied under conditions where regenerating axons were prevented from entering the chamber. This was accomplished by using an isolated segment of the nerve as a proximal insert. After one week, a cellular regenerate spanned the proximal and distal inserts. The size of the regenerate increased if circulation was preserved in the distal inserts. At four weeks, a perineurium-like sheath surrounded the regenerate and longitudinally oriented Schwann cell columns could be observed throughout the regenerate. A similar 'pseudo-nerve' formed towards a piece of distally inserted tendon. Thus, the information required for the formation of a nerve-like structure is inherent to the non-neuronal cells entering the chamber. Schwann cells, in contrast to regenerating axons, do not exhibit preferential growth towards nervous tissue.

Animals↗

Cellular contribution to supernumerary limbs resulting from the interaction between developing and regenerating tissues in the axolotl.

The relationship between limb development and limb regeneration is considered with regard to the mechanisms by which pattern is established during limb outgrowth. In a previous paper (Muneoka, K. and Bryant, S. V. 1982 Nature (London) 298, 369-371) the interaction between cells from the developing limb bud and the regenerating limb blastema was found to result in the production of organized supernumerary limb structures. In this paper the relative cellular contribution from developing and regenerating cells to supernumerary limbs resulting from contralateral grafts between limb buds and blastemas has been analyzed using the triploid cell marker in the axolotl. Results show that there is substantial participation from both developing and regenerating limb cells to all supernumerary limbs analyzed. These data lend further support to the hypothesis that developing and regenerating limbs utilize the same patterning mechanisms during limb outgrowth. This conclusion is discussed in terms of patterning models for developing and regenerating limbs and it is proposed that the rules of the polar coordinate model can best explain the behavior of cells during limb development as well as limb regeneration.

Ambystoma↗

Cellular behavior in the anteroposterior axis of the regenerating forelimb of the axolotl, Ambystoma mexicanum.

Cellular behavior along the anteroposterior axis of the regenerating axolotl forelimb was studied by use of triploid (3N) tissue grafted into diploid (2N) hosts and three-dimensional computer reconstructions. Asymmetrical upper forelimbs were surgically constructed with one half (anterior or posterior) 3N and the other half 2N. Limbs were amputated immediately after grafting or were permitted to heal for 5 or 30 days prior to amputation. When regenerates had attained the stage of digital outgrowth, the limbs were harvested and sectioned in the transverse axis for histological analysis. When all limbs bearing anterior grafts were considered as a group, 77% of the 3N mesodermal cells were observed in the anterior side of the regenerates and 23% were located in the posterior side of the regenerates. When all limbs bearing posterior grafts were considered as a group, 76% of the 3N mesodermal cells were found in the posterior side of the regenerate and 24% had crossed into the anterior side. Healing times of 0, 5, or 30 days prior to amputation had no effect on the experimental outcome. Three-dimensional computer reconstructions revealed that most 3N cells of mesodermal origin underwent short-distance migration from anterior to posterior or from posterior to anterior and intermixed with diploid mesodermal cells near the midpoint of the regenerated anteroposterior axis. Some 3N cells were observed at greater distances from the graft-host interface. By contrast, labeled epidermal cells from both anterior and posterior grafts exhibited long-distance migration across all surfaces of regenerated limbs. Details of a computer-assisted reconstructive method for studying the three-dimensional distribution of labeled cells in tissues are presented.

Ambystoma mexicanum↗

Axonal transport and release of transferrin in nerves of regenerating amphibian limbs.

Transferrin, a plasma protein required for proliferation of normal and malignant cells, is abundant in peripheral nerves of birds and mammals and becomes more concentrated in this tissue during nerve regeneration. We are testing the hypothesis that this factor is involved in the growth-promoting effect of nerves during the early, avascular phase of amphibian limb regeneration. A sensitive enzyme-linked immunosorbent assay for axolotl transferrin was developed and used to determine whether this protein meets certain criteria expected of the trophic factor(s) from nerves. During limb regeneration adult sciatic nerves greatly increased their content of transferrin, which immunohistochemistry revealed was distributed in both axons and Schwann cells. Using the double ligature method with sciatic nerves in vivo, it was determined that transferrin is carried by fast anterograde axonal transport at all stages of limb regeneration. An approach based on multicompartment organ culture demonstrated that fast-transported transferrin was secreted in physiologically significant amounts at distal ends of regenerating axons. Finally, the concentration of transferrin in the distal region of larval axolotl limb stumps was found to decrease directly and rapidly in response to axotomy. Since transferrin is important for both axonal regeneration and cell cycling, the present data have significance for various aspects of nerve's trophic activity during limb regeneration.

Ambystoma↗

Regulation of adherens junction protein expression in growth-activated 3T3 cells and in regenerating liver.

The expression of the adherens junction proteins vinculin, alpha-actinin, and talin was compared in serum-stimulated 3T3 cells and in regenerating rat liver following partial hepatectomy. The levels of vinculin RNA and protein synthesis were rapidly and transiently elevated in growth-activated fibroblasts (peaking at 2-3 h) and in regenerating liver (at 4-8 h), preceding the replicative stage. alpha-Actinin expression was also induced, but more slowly (peaking at 6-8 h in 3T3 cells and at 28 h in regenerating liver), and remained elevated when DNA synthesis was proceeding in both systems. The expression of talin RNA was only slightly elevated in 3T3 cells following serum stimulation, and it remained largely unchanged in regenerating liver. The levels of RNA coding for fibronectin and for the beta 1-integrin subunit were transiently and extensively induced during liver regeneration (fibronectin with a peak at 8 h and beta 1-integrin at 12 h). The uvomorulin RNA level, and the expression of the liver-specific genes albumin and transthyretin, decreased in regenerating liver. The results suggest a physiologically significant regulation in the expression of structural components which link the extracellular matrix to the microfilament system in growth-activated fibroblasts and in regenerating liver.

3T3 Cells↗

Comparison of newt lens regeneration stimulating activity in preparations of mammalian thyrotropin and fibroblast growth factor purified by various methods.

Irises of the newt Notophthalmus viridescens will regenerate a new lens in organ culture in the presence of the bovine thyrotropin preparation NIH-TSH-B8. It is not certain, however, whether thyrotropin itself is responsible for this stimulatory effect. To elucidate this problem further we compared the lens regeneration stimulating activity of thyrotropin preparations from several species, prepared by various methods. The lowest effective concentrations were approximately 3.0 micrograms ml-1 for the bovine NIH-TSH-B8 and 1.4 micrograms ml-1 for the ovine NIAMDD-oTSH-9 preparations. At those lowest concentrations, lenses with elongating lens fiber cells (stage 6) and enlarged lens fiber core (stage 8) were obtained, respectively, and the lens-fiber-specific protein gamma-crystallin was present in both cases. The crude bovine thyrotropin fraction, Sigma-TS-10, stimulated lens regeneration only at the highest concentration, 1400 micrograms ml-1. Bovine Pierce-bTSH, the purest thyrotropin preparation, stimulated lens regeneration sporadically at the lower concentration of 0.04 micrograms ml-1 up to the advanced stage 9 with large lens fiber core and flattened lens epithelium in one of nineteen irises. The pituitary fibroblast growth factor is a known contaminant of thyrotropin preparations. The preparation CR-FGF-40002 at concentrations between 0.001 and 0.1 microgram ml-1 did not promote lens regeneration. Therefore, the lens regeneration stimulating activity in thyrotropin preparations is not attributable to the fibroblast growth factor, and may also be independent of thyrotropin because the lens regeneration stimulating activity is not proportional to the thyrotropic activity in the preparations examined.

Animals↗