The Origin of a New Progenitor Stem Cell Group in Human Development.

The observation of two precursor groups of the early stem cells (Groups I and II) leads to the realization that a first amount of fetal stem cells (Group I) migrate from the AMG (Aortal-Mesonephric-Gonadal)-region into the aorta and its branching vessels. A second group (Group II) gains quite a new significance during human development. This group presents a specific developmental step which is found only in the human. This continuation of the early development along a different way indicates a general alteration of the stem cell biology. This changed process in the stem cell scene dominates the further development of the human stem cells. It remains unclear where this phylogenetic step first appears. By far not all advanced mammals show this second group of stem cells and their axonal migration. Essentially only primates seem to be involved in this special development.

[The immunomorphologic analysis of innervation of chromaffin paraganglian cells of the mammalian arteries and heart].

Innervation of chromaffin cells of paraganglia of the wall of mammalian large arterial vessels and heart (in rat, cat, and human) was studied by neuromorphological and immunohistochemical methods. There is established similarity in structure of specialized, "basket"-type nerve endings of the chromaffin cells (ChC) with pericellular nerve apparatuses of sympathetic and parasympathetic autonomic neurons. It is proposed to use immunohistochemical reaction for synaptophysin as method of selective detection of ChC of paraganglia and adrenal medulla. The conclusion is made that synaptophysin-positive terminals (SPPT) found on bodies of ChC and postganglionic neurons represent efferent, rather than afferent, synapses formed by myelinated axons of preganglionic fibers. It is suggested that ChC of paraganglia alongside with their characteristic endocrine function participate in complex mechanisms of chemoreceptor regulation of tissue homeostasis of mammalian blood vessels and heart.

[Nitric oxide formation by chromaffinocytes of respiratory system and its importance for catecholamine exocytosis]. / Obrazovanie okisi azota khromaffinotsitami organov dykhaniia i ee znachenie dlia ékzotsitoza katekholaminov.

Chromaffinocytes (both single and within paraganglia) located in larynx, trachea, extrapulmonary bronchi and lungs possess NADPH-diaphorase/NO-synthase activity. Chromaffinocytes and paraganglia are anatomically associated with the vagus, autonomous ganglia and the walls of small blood vessels. NO-synthase agonists, acethylcholine and Ca ionophore A23217, after intrapleural injection increase the enzyme activity, that is accompanied with the decrease of luminescence intensity and a reduction of monoamine content in cell cytoplasm. It is concluded that NO is involved in the mechanism of catecholamine release.

Steroid 5alpha-reductase type 1 immunolocalized in the rat peripheral nervous system and paraganglia.

Steroid 5alpha-reductase is an enzyme that converts a number of steroids with a C-4, 5 double bond and C-3 ketone to 5alpha-reduced metabolites. This enzyme has been suggested to play a role in brain development and myelination in the rat nervous system. In the present study, we examined the cellular and subcellular localization of the enzyme immunocytochemically in the rat peripheral nervous system and paraganglia using a polyclonal antibody against rat 5alpha-reductase type 1. Light and electron microscopical studies localized 5alpha-reductase in the Schwann cells of myelinated and unmyelinated nerve fibres, the satellite cells of the ganglia, the enteric glial cells and the supporting/sustentacular cells of the paraganglia. In the myelinated nerve fibres, immunoreactivity was observed in the outer loops, the nodes of Ranvier and the Schmidt-Lanterman incisures. Subcellularly, the immunoreactivity was localized in the cytoplasm of various glial cells. No immunoreactivity was observed in the myelin membrane, the axon or the neuronal perikaryon. These findings suggest that 5alpha-reductase is widely distributed in glial cells, and that, in addition to myelination, 5alpha-reduced steroids play a role in some glial functions in the peripheral nervous system.

Effects of 5-hydroxydopamine and 6-hydroxydopamine on the ultrastructure of type I cells in paraganglia of the rat recurrent laryngeal nerve.

The ultrastructure of the Type I cells in paraganglia of rat recurrent laryngeal nerve (RLN) was studied after the administration of 5-hydroxydopamine (5-OHDA) and 6-hydroxydopamine (6-OHDA). Normal Type I cells of RLN-paraganglia contained abundant organelles and their cytoplasm was characterized by the presence of numerous membrane-bounded dense-cored vesicles (DCVs). The DCVs were round in profile (diameter 107.67 +/- 0.06 nm, all values expressed as mean +/- s.e.m. in the present study) and possessed dense cores of moderate to low electron density. After 5-OHDA treatment (single injection, 100 mg/kg b.w., i.v.), the majority of DCVs were filled with a material of high electron density. No significant difference was observed between the profile diameter of the DCVs in 5-OHDA-treated rats (104.96 +/- 0.06 nm) and that in normal rats. After 6-OHDA treatment (three injections, 100 mg/kg b.w. each at 12 h intervals i.p.), no significant alteration in the electron density of the core was noted. However, most of the DCVs were enlarged and round, elliptical or irregular in profile (190.57 +/- 2.77 nm x 130.34 +/- 2.09 nm). The dense core of DCVs was centrally or eccentrically located in DCVs. The results of the present study indicate that: 1) there is only one type of granulated glomus cell (i.e., Type I cells) in the rat RLN-paraganglia under normal physiological condition; and 2) since the ultrastructural morphology of DCVs in Type I cells of rat RLN-paraganglia is altered after 5-OHDA or 6-OHDA treatment, these cells may possess mechanisms for the uptake of false adrenergic neurotransmitter and/or neurotoxin.

Adrenal chromaffin cells as transplants in animal models of Parkinson's disease.

The field of neural transplantation has moved rapidly forward in the last decade. Initially, fetal cells were used as implants to investigate their potential to ameliorate deficits in animal models of Parkinson's disease. However, because of the moral and legal problems associated with the use of fetal tissues in humans, alternative sources of donor tissue were sought which possessed the structural and functional characteristics needed to improve motor function in Parkinsonian patients. To date, one of the most promising tissues being investigated is the adrenal medulla, whose chromaffin cells possess an inherent plasticity of form and function. Transplanted chromaffin cells currently are being studied by a variety of approaches, including electron microscopy, in mouse, rat, and primate models of Parkinson's disease. An overview of the role of the chromaffin cell in this exciting and clinically important arena is briefly reviewed, with an emphasis on the fine structure of implanted chromaffin cells.

Vagal paraganglia of the rat.

Paraganglia are associated with every branch of the rat vagus nerve except the pharyngeal branch. Some of the paraganglia closely resemble the glomus caroticum, whereas others appear like small, intensely fluorescent (SIF) cells of autonomic ganglia. The paraganglionic cells of SIF cell-like bodies (SLB) store catecholamines (the most abundant is probably noradrenaline) and in some cases neurotensin. The innervation pattern of SLB is variable and their physiological role remains unclear. Paraganglionic cells of glomus-like bodies (GLB) predominantly store dopamine and probably also to a lesser extent noradrenaline. These putative chemoreceptor organs receive sensory innervation from nodose ganglion neurons as revealed by degeneration experiments and by anterograde neuronal tracing. Substance P- and calcitonin gene-related peptide-immunoreactive fibres seen in the region of vascular entry into the GLB may account for some of these sensory fibres, but the peptide/classical transmitter stored in sensory terminals synapsing on paraganglionic cells is unknown. Ultrastructural immunocytochemistry revealed vasoactive intestinal polypeptide (VIP)-immunoreactive fibres lying in the interstitial space between paraganglionic cells and large capillaries. These fibres may originate from VIP-immunoreactive neurons, being frequently attached to GLB. The major difference between GLB and the glomus caroticum concerns their blood supply and related innervation: Arteries and arterioles do not penetrate into GLB and, accordingly, noradrenaline- and neuropeptide Y-containing nerve fibres are lacking within GLB. This peculiar arrangement of paraganglionic parenchyma and arterial blood supply may be one of the reasons for the different physiological properties of vagal and carotid arterial chemoreceptors.

Development and plasticity of adrenal chromaffin cells: cues based on in vitro studies.

Neural crest derived precursors of the sympathoadrenal cell lineage give rise to two major cell types that differ in a number of morphological, ultrastructural, and biochemical characteristics: principal sympathetic neurons and chromaffin cells of the adrenal medulla. The present article reviews experimental studies performed on cultured adrenal medullary cells and designed to unravel the nature of epigenetic signals governing the developmental choice between the endocrine chromaffin and the neuronal sympathetic phenotype. Emphasis is placed on the role of glucocorticoids in initiation, development, and maintenance of the endocrine chromaffin phenotype and apparently antagonistic influences exerted by nerve growth factor (NGF) in vitro, resulting in the acquisition of neuronal properties by differentiated chromaffin cells. Experimental data from in vitro studies are compatible with the following conclusions. Glucocorticoids represent the decisive signal for the initial induction of endocrine differentiation. Moreover, high steroid hormone concentrations, as present in the adrenal medulla, are a prerequisite for the maturation of chromaffin cells. Even in a differentiated state, the endocrine phenotype is unstable in the absence of glucocorticoids, and the cells seem to reenter the neuronal developmental pathway. Under these conditions, cellular survival and differentiation into sympathetic neurons become NGF-dependent, as in normal sympathetic development. Thus, the effects of NGF survival, neurite outgrowth, and transmitter synthesis of cultured chromaffin cells probably do not reflect the induction of a specific phenotype, but they may be interpreted as a general neurotrophic support observable with other responsive cell types.

The cytoplasmic matrix of the adrenal chromaffin cells of rats under normal and stressed conditions.

In embedment-free electron microscopy with polyethylene glycol embedding and subsequent deembedding, the conventional cytoplasm of the chromaffin cells was revealed to consist of a three-dimensional lattice of microtrabeculae and gives the impression that the chromaffin granules are held in place by the lattice. After the restraint stress, a substantial number of chromaffin cells were almost free of granules, and the microtrabecular lattice was much more compact than that in cytoplasmic regions occupied with remaining granules or increased mitochondria. In immunocytochemistry, actin immunofluorescence was confined to the subplasmalemmal regions, while tubulin and tropomyosin immunofluorescence appeared throughout the entire cytoplasm of normal chromaffin cells. After the stress, the immunofluorescence for actin and tubulin increased in intensity, while that for tropomyosin decreased. Immunogold labelings for actin and tubulin were found mainly on the thinner subplasmalemmal microtrabeculae and the thicker perikaryal ones, respectively, while some were deposited in the form of small aggregates on portions of microtrabeculae. No specific association between the gold labelings for actin or tubulin and the chromaffin granules was found, even in the subplasmalemmal regions. A hypothetical interpretation was proposed in which a more compact lattice of the microtrabeculae in spatial association with a looser lattice represents a gelated state of the cytoplasm. The significance of the gel-sol transition of the cytoplasmic matrix in relation to the secretory mechanism was discussed.

Histomorphometric and morphologic studies of the carotid body and aortic paragangliomas.

Morphometric and morphological parameters have been evaluated in tumours of carotid body paraganglia and of aorticopulmonary and aorticosympathetic paraganglia. Paragangliomas are characterized by a higher cell density and rounder nuclei (roundness factor) than non-neoplastic carotid body paraganglia. The nuclear area has similar mean values in tumours and normal paraganglia; however, the former group shows higher standard deviation values and coefficients of variation, reflecting the fact that paragangliomas have nuclei of variable size; the variation is more pronounced in aorticopulmonary and aortico-sympathetic paragangliomas. However, subgroups on the basis of morphological features (architectural patterns and degree of intensity of argyrophilia), site of origin, and clinical behaviour (metastases and recurrences) show no morphometric differences.

Intra and juxtavagal paraganglia: a topographical, histochemical, and ultrastructural study in the human.

The topographical, ultrastructural, and histochemical features of 23 human vagal paraganglia were analyzed. Nineteen of the 23 paraganglia were found in previously unreported sites; 18 of the 19 were in the cervical part of the nerve, between the carotid bifurcation and the superior thoraco-cervical inlet, and one paraganglion was located in the retrothyroidal part of the left inferior laryngeal nerve. The results of ultrastructural studies (2 cases), the histochemical and formaldehyde-induced-fluorescence studies (3 cases), and specific acetylcholinesterase activity (one case) demonstrate that these structures fulfill many of the modern criteria for paraganglionic tissue. In addition to paraganglia, single, isolated neurons or true micro-ganglia were always found along the trunk and branches of the vagus nerve when multiple sections were examined.

Paragânglios intraganglionares em coraçöes humanos adultos / Intraganglionic paraganglia in adult human hearts

Descrevem-se dois paragânglios intraganglionares observados em coraçöes de homens adultos, aparentemente sadios, que tiveram morte violenta. Os paragânglios assim localizados poderiam relacionar-se ao controle da funçäo ganglionar

Light- and electron-microscopic demonstration of enkephalin-like immunoreactivity in paraganglia of the human urinary bladder.

The distribution of enkephalin-like immunoreactivity in paraganglia of the urinary bladder of adult humans was studied by use of immuno-electron microscopy. All paraganglionic cells were positively stained. Enkephalin-like immunoreactivity was located in chromaffin granules. Chromaffin cells in the paraganglia showed only few degenerative features, suggesting undisturbed function of the cells.

The ultrastructure of hypertrophied paraganglia in aged rats.

The catecholamine-storing cells in the paraganglia of old rats showed structural characteristics common to adrenomedullary and paraganglionic cells of young animals. No sign of degeneration was found. Lipofuscin pigment was observed in most cells. The paraganglia were innervated and well supplied by fenestrated sinusoidal capillaries. Their fine structure suggests active endocrine function. An increase in the total bulk of the paraganglia in old rats suggests that they have a physiological role in senescence.

Ultrastructure and histochemistry of human SIF cells and paraganglia.

The FIF method and electron microscopy were used to study SIF cells in the human sympathetic ganglia. In serial sections SIF cells in one ganglion often numbered less than 30, although they were found in every ganglion examined. Microspectrofluorimetry demonstrated the high catecholamine content in SIF cells. Electron microscopically these cells appeared as small granule-containing cells that receive a rich cholinergic type innervation. The diameter of the storage granules was 300 to 400 nm. In addition the SIF cells had close connections with each other. The SIF cells, situated solitary or as small clusters, were surrounded by satellite cells. Frequently the SIF cells located close to blood vessels.

Ultrastructure and possible function of an atrial paraganglion not directly related to atrial ganglion in the albino mouse.

The ultrastructure of a paraganglion found in right atrium of albino mouse close to the superior cava vein is described. A capillary, which occupied the central part of the paraganglion, was surrounded by three chromaffin cells. Two other chromaffin cells were also present, but neither nerve fibers nor nerve endings were seen. The possible physiological role of paraganglia is discussed.

Paraganglia of the bladder.

Normal paraganglia containing high amounts of catecholamines are a constant feature of the wall of the bladder in elderly men. The paraganglia in this location might give rise to pheochromocytomas. The importance of the local endocrine effects in the regulation of the muscular tone in the bladder is discussed.