Histology and histopathology Vol.13, nº 4 (1998)

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Open Access
The effect of thymic inoculation to induce tolerance of allogeneic thyroid grafts in the outbred rabbit
(Murcia : F. Hernández, 1998) Torchia, M.G.; Aitken, R.M.; Thliveris, A.
Many studies have demonstrated that allograft tolerance can be achieved in inbred rats and mice following intrathymic injection of donor cells or antigen and treatment with antilymphocyte serum (ALS). In outbred dogs, xenografts, and inbred rat strains with major MHC antigen difference, tolerance has not similarly been induced. The focus of this study was to determine whether allogeneic thyroid graft tolerance could be achieved in outbred rabbits. In the experimental group (n=5), recipients received an intrathymic injection of donor lymphocytes and a single treatment of ALS. Controls (n=5) received intrathymic cell culture medium and ALS treatment. Donor-recipient allogenicity was monitored with mixed lymphocyte culture (MLC) over 18 weeks. Donor thyroid tissue was placed into recipient gluteal muscle fibres one week following the last MLC measurement. A third group of rabbits (n=4) received thyroid autografts without any other treatment. There were no differences in MLC stimulation indices (SI) between the control and experimental group nor did MLC (SI) change within groups. All thyroid autografts survived the two week monitoring period and demonstrated normal appearing thyroid follicles on histologic examination. All thyroid allografts showed severe acute rejection reactions on biopsy within one week. Further studies using outbred animals to examine the role of thymic inoculation are required to determine whether similar techniques might be successful in the human.
Open Access
Localization of thrombospondin-l and its cysteine-serine-valine-threonine-cysteine-glycine receptor in colonic anastomotic healing tissue
(Murcia : F. Hernández, 1998) Roth, J.J.; Buckmire, M.A.; Rolandelli, R.H.; Granick, M.S.; Tuszynski, G.P.
Thrombospondin-l (TSP-1) is a matrix protein implicated in mechanisms of wound healing. TSP-1 contains the sequence cysteine-serine-valinethreonine- cysteine-glycine (CSVTCG) that has been shown to function primarily as a cell adhesion domain. Our laboratory has isolated a novel receptor specific for the CSVTCG adhesive domain of TSP-1. Immunohistochemical staining techniques and computerized image analysis were used to identify and quantitate TSP-1 and its CSVTCG receptor in surgically created colon anastomotic wounds. Histopathologic and quantitative examination demonstrated increased expression of TSP- 1 and its CSVTCG receptor in areas of wound healing. These findings suggest a role for TSP-1 and its CSVTCG receptor in wound healing. The control of expression and activity of these molecules may eventually be the basis for the development of wound healing agents that could significantly reduce the morbidity from surgical intervention.
Open Access
Paravertebral muscles in experimental scoliosis, a light and electron microscopic study
(Murcia : F. Hernández, 1998) Garrosa, M.; Fernández-Mariño, J.R.; Gayoso Rodriguez, Manuel J.; Tomey, M.J.; Al-Majdalawi, A.; Rodríguez, L.P.
Experimental! structural dextroconvex scoliosis was produced in rabbits by costotransversolisis with transversectomy and releasing of paravertebral muscles between TVII and TX on the right side. Two compensatory curves developed on the upper dorsal and lumbar levels. Biopsies of paravertebral muscles in experimental animals included, besides areas of normal tissue, a considerable derangement of the cell contractile apparatus with sarcoplasmic dilation and eventual cell disintegration and necrosis. Histological changes varied along levels, the convexit!~ being more affected. The severity of changes and retiuction in body weight and length were correlated with the degree of scoliosis. A selective atrophy of slow-twitch fibers was observed in experimental animals, especially at the level of the main curve, whereas fast-twitch fiber atrophy was more important caudally. Control animal biopsies always appeared normal. Our experimental model shows an overt participation of paravertebral muscles in the establishment of compens,atory processes following scoliosis, although the role that paravertebral muscles play in the etiopathogenesis of human idiopathic scoliosis requires further investigation.
Open Access
Cell proliferation and cancer
(Murcia : F. Hernández, 1998) Lopez-Saez, J.F.; De la Torre, C.; Pincheira, J.; Gimenez-Martin, G.
The discovery that phosphorylation of selected proteins by cyclin-dependent kinases is the engine which makes the cycle run provides a new image of the control of proliferation and of its deregulation. The high conservation of this machinery in the different eukaryotic organisms emphasizes its early origin and its importance for life. It also makes the extrapolation of findings between different species feasible. The control of proliferation relies basically on accelerating and braking mechanisms which act on the engine driving the cycle. This review particularly stresses the importance of checkpoint or tumor suppressor pathways as transduction systems of negative signals which may induce a cycle braking operation. They prevent any important cycle transition, as the initiation of proliferation, that of replication, mitosis, etc., until the DNA and other cellular conditions make such a progression safe. These checkpoint pathways are able to recognize and transduce signals about the adequacy of initiating or continuing proliferation for a cell at a particular time, under a particular set of external and internal conditions. Crucial components of these pathways are proteins encoded by some of the checkpoint genes that evaluate the final balance of mitogenic and antimitogenic pathways reaching them and, if the balance is negative, they prevent temporarily cycle inititation or its progression by inhibiting the corresponding cyclin-dependent kinases. On the other hand, when the balance becomes positive, they allow the activation of the cyclin-dependent kinases. Uncontrolled cell proliferation associated with cancer always depends on the functional abrogation of at least one of the checkpoint pathways. The checkpoint or tumor suppressor protein p53 is one of the proteins in them, and mutations in the gene encoding it are present in more than half of all human tumours. The review touches new pharmacological strategies which have been opened by the discovery of portions of some of the Offprint requests to: Prof. Dr. Jorge F. Lopez-Saez, Departamento de Biologia, Universidad Autonoma de Madrid, Canto Blanco, E-28049 Madrid, Spain *This review is dedicated to Jesljs Vazquez, a great teacher, a great histopathologist and, overall, a great man who left us prematurely. signal transduction cascades involved in the transient brake of cell proliferation. Restoration of checkpoint pathways either prevents further proliferation of cells with damaged genome until repair is over or, alternatively, the dismantling of these checkpoints induce those cells to commit suicide (apoptosis). The fact that both restoration and dismantling of checkpoint pathways sensitive to DNA damage have not disturbing effects on any other proliferating cell with undamaged DNA makes these selective strategies promissing.
Open Access
Insulin receptors and signal transduction proteins in the hypothalamo-hypophyseal system, a review on morphological...
(Murcia : F. Hernández, 1998) Unger, J.W.; Betz, M.
Receptors for insulin are widely distributed in the brain and pituitary. The current hypothesis on receptor function in these regions points to a role of insulin as a mediator in the communication of the peripheral endocrine system with the brain via various steps of the neuroendocrine axis. Recent data demonstrate that receptor-positive neurons in the brain, i.e. in the hypothalamus, and secretory cells in the anterior pituitary gland possess specific proteins that are thought to be involved in key steps of post receptor signal transduction, in particular insulin receptor substrate-1 and phosphatidylinositol 3'-kinase (PI3k). PI3k is a critical enzyme of the intracellular signaling pathway that is activated by a number of receptor tyrosine kinases, including receptors for insulin and IGF- 1. This information further completes the framework indicating in vivo activity of insulin receptors in central neuroendocrine cells and their involvement in one branch of several physiological mechanisms that control body metabolism and nutritional behaviour.
Open Access
The nature and implication of intestinal endocrine cell changes in coeliac disease
(Murcia : F. Hernández, 1998) El-Salhy, M.
Coeliac disease is associated with intestinal lesion. This lesion causes architectural derangement of the mucosa in the form of villus atrophy, increased crypt length and increased volume of the lamina propria. Several changes in the intestinal endocrine cells have been reported over the years, e.g. the number of secretin cells and increased numbers of GIP, CCKIgastrin, motilin, and serotonin cells. There is no consensus about the nature of the changes in somatostatin-cells. It has been postulated that the changes in the endocrine cells are a selective process to meet the new demands exerted by the dramatic decrease in intestinal absorptive area. It has been speculated further that the changes in the endocrine cells would cause an incomplete digestion of the ingested food and its rapid elimination from the intestine. These changes may be responsible for the diarrhoea and steatorrhoea that occur in patients with coeliac disease.
Open Access
Retinal and lenticular ultrastructure in the aestivating salamanderfish, Lepidogalaxias salamandroides (Galaxiidae, Teleostei) with special reference to a new type of photoreceptor mosaic
(Murcia : F. Hernández, 1998) Collin, S.P.; Collin, H.B.
The salamanderfish, Lepidogalaxias salamarzdroides (Galaxiidae, Teleostei) is endemic to southwestern Australia and inhabits shallow, freshwater pools which evaporate during the hot summer months. Burrowing into the substrate in response to falling water levels allows these fish to aestivate for extended periods of time while encapsulated in a mucous cocoon even when the pools contain no water. Only a few minutes after a major rainfall, these fish emerge into relatively clear water which subsequently becomes laden with tannin, turning the water black and reducing the pH to approximately 4.3. As part of a large study of the visual adaptations of this unique species, the retinal and lenticular morphology of the aestivating salamanderfish is examined at the level of the light and electron microscopes. The inner retina is highly vascularised by a complex system of vitreal blood vessels, while the outer retina receives a blood supply by diffusion from a choriocapillaris. This increased retinal blood supply may be an adaptation for reducing the oxygen tension during critical periods of aestivation. Large numbers of Miiller cells traverse the thickness of the retina from the inner to the outer limiting membranes. The ganglion cells are arranged in two ill-defined layers, separated from a thick inner nuclear layer containing two layers of horizontal cells by a soma-free inner plexiform layer. The photoreceptors can be divided into three types typical of many early actinopterygian representatives; equal double cones, small single cones and large rods (2:1:1). These photoreceptors are arranged into a unique regular square mosaic comprising a large rod bordered by four equal double cones with a small single cone located at the corner of each repeating unit. The double cones may optimise perception of mobile prey which it tracks by flexion of its head and "neck" and the large rods may Offprint requests to: Dr. Shaun P. Collin, Marine Neurobiology Laboratory. Department of Zoology, University of Western Australia, Nedlands 6907, Western Australia, Australia. Fax: (08) 9380 1029. ernail: scollin@cyllene.uwa.edu.au increase sensitivity in the dark tannin-rich waters in which it lives. Each single cone also possesses a dense collection of polysomes and glycogen (a paraboloid) beneath its ellipsoid, the first such finding in teleosts. The retinal pigment epithelium possesses melanosomes, phagocytes and a large number of mitochondria. The anatomy of the retina and the photoreceptor mosaic is discussed in relation to the primitive phylogeny of this species and its unique life history.
Open Access
Ultrastructure of the parathyroid gland of the young golden hamster after short-term treatment with ethanol
(Murcia : F. Hernández, 1998) chen, H.; Hayakawa, D.; Emura, S.; Tamada, A.; Jamali, M.; Yamahira, T.; Yoshida-Terasawa, K.; Isono, H.; Shoumura, S.
We studied the ultrastructure of the parathyroid gland of young golden hamsters after short-term treatment with ethanol (1.5 gkg bw or 6.0 gkg bw). We did not find any ultrastructural changes of the parathyroid gland after administration of 1.5 g/kg ethanol. In the hamsters, 3 hours after administration of 6.0 g!kg ethanol, the mean serum calcium concentration was significantly low as compared to that of the control animals. In the parathyroid gland 1 hour after administration of 6.0 glkg ethanol, the Golgi complexes associated with a few prosecretory granules and the volume density occupied by the Golgi complexes decreased compared with that of the control animals. In the parathyroid glands 3 hours after administration of 6.0 g/kg ethanol, the Golgi complexes decreased as compared with those of the control animals, while the large vacuolar bodies increased. These findings suggest that the cellular activity of the parathyroid gland is suppressed after short-term treatment with ethanol. Intracellular lumen was found in the parathyroid chief cells 3 hours after administration of 6.0 &kg ethanol, and the significance of this structure is discussed.
Open Access
Immunolocalization of regulatory peptides and 5-HT in bovine male urogenital apparatus
(Murcia : F. Hernández, 1998) Arrighi, S.; Domeneghini, C.
Specimens of testis, excurrent duct including the accessory genital glands and urethra throughout its extension were investigated in adult bovines, in order to imm~~nohistochemicalllyo calize both the peptidergic innervation and the epithelial cell types belonging to [he diffuse endocrine system (DES). Immunoreactivities to GRP, met- and leu-enkephalins, CGRP, NPY, substance P, VIP, somatostatin, l3-endorphin and 5-HT antisera were tested by means of a labelled streptavidin-biotin (LSAB) method. Such regulatory substances were found in components of the peripheral nervous system (nerve fibers in the connective and muscular tissues, sub- and intraepithelial nerve terminals, nerve cell bodies and fibers in intramural ganglia), and in epithelia1 endocrine/ paracrine cells. Bovine urogenital apparatus is supplied by many peptide-containing nerves, which contain in many localizations GRP and enkephalins, and to a lesser extent substance P, CGRP, NPY and VIP. A thin network of peptidergic nerves distributes to the musculature of the canalicular organs and accessory glands. The prostatic complex was especially rich in peptidergic innervation, and also contained somatostatin- and 5-HTsecreting endocrine cells. In addition, 5-HT-immunoreactive endocrine cells were found in the bulbourethral gland and urethral epithelium. CGRP-ir nerves were present contacting striated muscle fibers of urethra (motor end plates). The testis was devoid of any immunoreactivity. These data are compared with those obtained in a companion study carried out the same organs in two species of Equidae (Equus caballus and Equt~sa sinus). Different patterns of immunoreactivities can be outlined in these domestic ungulates.
Open Access
Glutamate-like immunoreactivity in axon terminals from the olfactory bulb to the piriform cortex
(Murcia : F. Hernández, 1998) Hennequet, L.; Gondra, J.; Sendino, J.; Ortega, F.
A highly specific anti-glutamate monoclonal antibody, mAb2D7, was used together with light and electron microscopy to elucidate the role played by the amino acid glutamate in the projection from the olfactory bulb to the piriform cortex in the rat. By light microscopy, glutamate-like immunoreactivity was observed in neuronal cell bodies and in the neuropil of the piriform cortex. Double labelling experiments which involved injections of wheat germ agglutinin-horseradish peroxidase into the olfactory bulb and a postembedding immunogold method for electron microscopy revealed anterogradely labelled terminals making asymmetric synaptic contacts on dendrites in the piriform cortex which contained high levels of glutamate as assessed by quantification. These results further support a role for glutamate as a neurotransmitter in the efferent pathway of the rat olfactory bulb.
Open Access
Distribution of central catecholaminergic neurons, a comparison between ungulates, humans and other species
(Murcia : F. Hernández, 1998) Tillet, Y.; Kitahama, K.
In ungulates and primates, the distribution of central catecholaminergic neurons identified using antibodies raised against catecholamine synthesizing enzymes and catecholamines themselves, shows many differences if compared to rats. Catecholaminergic neurons are more loosely clustered in ungulates and primates than in rat. In the medulla oblongata, the density of noradrenergicladrenergic neurons is lower in ungulates than in other species and, particularly in sheep, the adrenergic group C1 is not observed. The noradrenergic neurons of the locus coeruleus are present in a larger area in ungulates than in rodents. In the hypothalamus, the density of dopamine neurons is lower in ungulates and primates than in rodents. In the rostra1 hypothalamus of ungulates, the dorsal part of the group A14 is missing, and these species present only the ventral part of the group A15. In primates the group A15 extends into the supraoptic and paraventricular nuclei which have large tyrosine hydroxylase-immunoreactive (TH-IR) neurons not observed in other species. In addition, in all studied species, not all cells expressing catecholamine synthesizing enzymes also express catecholamines, as found in some TH-IR neurons in the arcuate nucleus, thereby demonstrating the necessity of using different markers to ascertain the true catecholaminergic nature of labeled neurons. These anatomical differences between species show the difficulty in extrapolating the distribution of catecholamine neurons from one species to another and may be related to adaptative physiological differences between mammals.
Open Access
Colocalization of tumor necrosis factor-alpha and nitric oxide-synthase immunoreactivity in mast cell granules of nasal mucosa
(Murcia : F. Hernández, 1998) Bacci, S.; Rucci, L.; Riccardi-Arbi, R.; Borghi-Cirri, M.B.
We have demonstrated, with immunohistochemical techniques, the colocalization of tumour necrosis factor-a (TNFa) with a constitutive neuronal isoform of nitric oxide-synthase (NOS) in granules of the majority (52.77%) of the mast cells (MCs) of healthy human nasal mucosa. Very few cells were positive for NOS alone (2.54%). Some cells were positive for TNFa alone (16.73%) or negative for both antigens (18%). Since dim degranulation occurs in MCs of healthy nasal mucosa at any time, we propose that low concentrations of TNFa and NOS secreted by these cells are involved not only in the regulation of homeostasis of normal human nasal mucosa, but also in the survival and function of MCs themselves.
Open Access
Peanut lectin-binding sites and mucins in benign and malignant colorectal tissues associated with schistomatosis
(Murcia : F. Hernández, 1998) Lin, M.; Hanai, J.; Gui, L.
An immunohistochemical and histochemical comparative study was carried out in benign and malignant colorectal tissues with and without schistosomiasis. This included a quantitative determination of peanut lectin (PNA)-binding sites and proliferating cell nuclear antigen (PCNA) expression and histochemical detection of mucin changes. 133 cases were studied, including 70 cases of colorectal carcinoma associated with schistosomiasis (CCS) and 63 cases of colorectal carcinoma without schistosomiasis (CC). Significant differences were found in the type of mucin-containing carcinomas (MC) between CCS and CC. 65% of nontumorous mucosa adjacent to MC of the CCS group expressed PNA-binding sites, significantly higher than those of the MC in the CC group (31%). The nontumorous mucosa in cases of MC of the CCS group also showed a high percentage of sialomucin-predominant secretion (69%, vs 38% in MC of the CC group). Consistently, the presence of PNA-binding sites in MC tumors of the CCS group was increased, compared with that in the same subtype in the CC group (respectively 65% and 31% of strong positivity for PNA). However, no differences in expression of PNA and mucin changes were demonstrated in the surrounding mucosa and tumorous tissues of non-mucin-containing carcinomas (NMC) between CCS and CC. The expression of PCNA was not different between CCS and CC and their subtypes. Our findings suggest a close relationship between mucin-containing colorectal carcinomas and schistosomiasis japonica.
Open Access
Do adhesion molecules importantly regulate leukocyte kinetics within intraacinar microvessels of the lung.
(Murcia : F. Hernández, 1998) Yamaguchi, K.; Nishio, K.; Aoki, T.; Suzuki, Y.; Sato, N.; Takeshita, K.; Kudo, H.
Precise assessment of blood cell kinetics in the pulmonary microcirculation is extremely difficult because pulmonary microvascular architecture contains arterioles, venules and capillaries in an exceedingly intricate and densely convoluted fashion. Conventional epiluminescence microscopy may not be suitable for investigation of blood cell kinetics in the pulmonary microcirculation, in which arterioles, venules and capillary networks are not located in the same plane. To overcome these impediments, we recently developed a real-time confocal laser luminescence microscope with a high-speed analysis component having the capacity to yield confocal-images of rapidly moving cells at a rate of 1,000 frameslsec and at sufficiently high magnification. In the current review, we will first introduce the details of our newly developed observation system constructed with a view to estimation of blood cell dynamics in the intraacinar microcirculation of the lung. Applying this novel method to isolated perfused rat lungs, we will secondly address the issue of whether or not leukocyte-endothelium interactions in the pulmonary microcirculation qualitatively differ from those serving in the systemic microcirculation. We will particularly shed light on possible roles of endothelial ICAM-1, endothelial P-selectin and leukocyte L-selectin in distorting leukocyte kinetics in the intraacinar microvessels under a variety of diseased conditions, including prolonged exposure to a hyperoxic environment inducing a significant upregulation of ICAM-1 as well as P-selectin on the pulmonary microvascular endothelium, and stimulation of leukocytes by an IL-8 analog causing downregulation of leukocyte L-selectin but inverse upregulation of CD18-related integrins.
Open Access
Expression of differentiation-related genes in colorectal cancer, possible implications for prognosis
(Murcia : F. Hernández, 1998) van Belzen, N.; Dinjens, W.N.M.; Eussen, B.H.J.
Although differentiation grade is an important prognostic factor for colorectal tumors, its usefulness is limited since its predictive value for tumor behavior is not very significant. This might be related to the subjective nature of histological assessment of differentiation grade, which allows the distinction of only three grades, and with limited reproducibility. Characterization of the differentiation process at the biochemical level may improve our understanding of normal and malignant differentiation, and is expected to provide molecular markers with higher discriminative potential than histomorphology. Several studies have compared gene expression in undifferentiated and differentiated colon carcinoma c e l l s , and many differentially expressed genes have been identified. Some of these, including HLA class I, nucleophosmin, adenylosuccinate lyase, a-tubulin, and a novel gene designated Drgl, were found to be expressed at different levels in neoplastic as compared to normal tissue. In this review the rationale, implementation, and results of this approach are discussed, as well as the characteristics of two novel differentially expressed genes, ICTl (previously named DS-1) and Drgl .
Open Access
Different putative neuromodulators are present in the nerves which distribute to the teleost skeletal muscle
(Murcia : F. Hernández, 1998) Radaelli, G.; Domeneghini, C.; Arrighi, S.; Mascarello, F.; Veggetti, A.
The presence of putative neuromodulators in the nerve fibres was investigated in white skeletal muscle of two teleost fish not taxonomically correlated and showing different patterns of innervation (multiple versus focal innervation). Cryostat sections of epaxial, hypaxial and adductor mandibulae (AM) muscles of Sparus aurata and Anguilla anguilla were stained histochemically for reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase. Other sections were used for indirect immunohistochemistry (streptavidin-biotin and rhodamine immunofluorescence methods), employing antibodies specific for putative excitatory or inhibitory peptides, including CGRP, substance P, met-enkephalin, bombesin, and VIP. In addition, ultrastructural observations were performed in order to describe the morphology of the motor endplates. A strong immunoreactivity for CGRP and substance P was found in many nerve terminals. Met-enkephalin, bombesin and VIP immunoreactivities were less frequently observed. No immunoreactivity was observed to CCK, NPY or 5-HT. NADPH-diaphorase was identified in nerve fibres of the AM complex only of A. anguilla. Electron microscopy observations evidenced more than one type of synaptic vesicle in motor endplates. Some differences in putative neuromodulator distributions were observed in the two species and muscle complexes, which may be related to the different taxonomical position as well as the different pattern of innervation of white muscle fibres.
Open Access
The synaptic process in Locusta migratoria spermatocytes by synaptonemal complex analysis
(Murcia : F. Hernández, 1998) Molina, J.; Martínez Flores, I.; Templado, C,; García, M.; Egozcue, J.
We describe the synaptic process during meiotic prophase in spermatocytes from Locusta migratoria, using synaptonemal complex (SC) spreads analyzed by light (LM) and electron (EM) microscopy. At leptotene, a stage of short duration, unpaired axial elements begin to be assembled. Synapsis starts at zygotene, beginning usually at the terminal regions of the bivalents, either at the proximal, centromeric end or at the distal, non-centromeric end; interstitial initiation of synapsis was only occasionally observed in the longer chromosomes. Pairing is asynchronous, and shorter chromosomes are the first to complete synapsis. At pachytene all bivalents are fully synapsed. Diplotene is characterized by the progressive fragmentation of SCs; fragmentation is asynchronous, and affects mainly the longer chromosomes, while the shorter ones maintain their morphology up to late diplotene.
Open Access
Methylene blue supravital staining, an evaluation of its applicability to the mammalian brain and pineal gland
(Murcia : F. Hernández, 1998) Müller, T.
Methylene blue supravital staining of mammalian brain reveals typical staining patterns in different brain regions. Within the cerebellum of the mouse, the dye showed a peculiar affinity for the somata and the axons of Purkinje cells. Additionally, large polymorphic neurons characterized by long descending axons were detected within the granular layer and the white matter. These cells might represent another type of projection neuron. In the stratum pyramidale and stratum oriens of the murine hippocampus, a subpopulation of non-pyramidal cells, i.e. intrinsic interneurons, were selectively stained. Additionally, a labelling of perineuronal nets of extracellular matrix covering single cells could be achieved; this phenomenon might be due to the occurrence of strong anionic residues which attract the cationic dye. Therefore, perineuronal nets might also trap other cations and play an important role in the control of cell excitability. The electron microscopic investigation revealed drop-like dye accumulations within the cytoplasm and a staining of material at the site of the plasma membrane. Throughout the pineal gland, a network of a subpopulation of polymorphic cells with manifold long processes could be visualized. Syncytial connections of cells seemed to occur. The oxygendependent selective staining is probably functionally connected with the generation of oxygen radicals and subsequent oxidative stress for the cells. This reaction indicates a certain vulnerability to hypoxia; therefore, the intracellular dye-uptake might be interpreted as an early sign of metabolic disturbance.
Open Access
Otoconia biogenesis, phylogeny, composition and functional attributes
(Murcia : F. Hernández, 1998) Fermin, C.D.; Lychakovs, D.; Campos, Antonio; Hara, H.; Sondag, E.; Jones, T.; Jones, S.; Taylor, M.; Meza Ruíz, G.; Martín, D.S.
This work consolidates data about these interesting organic crystals of vertebrate inner ears. It addresses 5 aspects of inner ear otoliths not completely understood to date: 1) embryological data that explains the formation of the crystals, 2) the significance of the organic and the inorganic phase of the otolith and the changing patterns of otoconia formation along the evolutionary tree, 3) otoliths contribution for detecting linear acceleration, 4) the effect that altered gravity and aminoglycosides have on the development and adult shape of the crystals, and the evolutionary significance of a changing shape of the crystals from primitive forms (lamprey) to high vertebrate birds and mammals is discussed, 5) functional attributes of the otolithic organs and morphological modifications of the otoliths by physical and chemical insults are presented with an extensive discussion of the most relevant literature published and available to us.
Open Access
Molecular changes in human melanoma metastasis
(Murcia : F. Hernández, 1998) Luca, M.R.; Bar-Eli, M.
The molecular changes associated with the transition of melanoma cells from radial growth phase to vertical growth phase (metastatic phenotype) are not well defined. Our recent studies have demonstrated that the two tumor suppressor genes, p53 and p16/CDKN2, do not play a major role in the acquisition of the metastatic phenotype in human melanoma. Mutations in p53 are infrequent and do not correlate with the metastatic potential of human melanoma cells while p161CDKN2 abnormalities are frequent, but are not prerequisite for the acquistion of the metastatic phenotype. On the other hand, the tyrosine-kinase receptor c-KIT and the cell adhesion molecule MCAMIMUC-18 play active roles in the progression of human melanoma. Metastatic melanoma cells overexpress MCAM and do not express the c-KIT receptor. Enforced c-KIT expression in metastatic cells significantly inhibited their growth and metastatic potential in nude mice. Furthermore, exposure of c-KIT-positive melanoma cells in vitro and in vivo to stem cell factor (SCF), the ligand for c-KIT, triggered apoptosis of these cells but not of normal melanocytes. Ectopic expression of MCAM into primary cutaneous melanoma cells enhanced their tumorigenicity and met$static ability in vivo. We found that both genes, c-KIT and MCAM, are regulated by the transcription factor AP-2 and that metastatic melanoma cells do not express AP-2. We therefore propose that loss of AP-2 might be a crucial event in the progression of human melanoma.