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G Alonso

Publications and source records attributed to G Alonso.

At least 73 records · Page 4Linked to original sources
PubMed1997

Clustering of KV4.2 potassium channels in postsynaptic membrane of rat supraoptic neurons: an ultrastructural study.

Ion channels play a key role in determining both neuronal membrane excitability and specificity. Neuronal specificity is achieved by several mechanisms, including the properties of the afferent network neurons are involved in, and the expression of specific sets of ion channels at the cellular level. In addition, subcellular distribution of channels might contribute to neuronal specificity, as suggested by the growing number of recent studies. Among ion channels, potassium (K+) channels have been shown to play an essential contribution in repolarization and interspike duration. Recently, K+ channel subtypes examined by light microscopy were reported to display a differential subcellular distribution in central neurons. But the precise localization of the channels on pre- or post-synaptic membrane was only assessed in a few brain areas. Here we used confocal and immunoelectron microscopic approaches to determine the hypothalamic localization of Kv4.2 K+ channels, which encode an A-type current. We found that intense immunostaining was localized to the supraoptic nucleus where it frequently formed rings outlining the somata of magnocellular neurons. Electron microscopy further revealed that this immunostaining was essentially associated with the plasma membrane limitating the somata or the dendrites of these neurons, and that it was particularly concentrated at the site of synaptic contacts. This is the first report showing clusters of voltage-gated channels on postsynaptic membranes in central mammalian neurons. The specific localization of the Kv4.2 channel indicates that this channel may play a role in signal integration at the synapse.

Animals↗
PubMed1997

Cloning of the PacB-Ter region from plasmid Mip233 (IncHI3) and their expression in E. coli ton, tol mutants.

A region of the plasmid Mip233 (incompatibility group HI3) encoding the phenotypes of resistance to the channel-forming colicins (character PacB) and potassium tellurite (Ter), was cloned and studied. Both properties are contained in an insert of 2.2 Kbp, being the smallest functional clone (pB22) isolated so far. E. coli DH5 alpha pB22 transformants exhibit resistance to the colicins as well as to high levels of tellurite (> 1000 micrograms ml-1). Results suggest that they are genetically linked forming an inducible operon. pB22 does not show significant homology with DNA from other H plasmids. Tests using E. coli ton and tol mutants harbouring recombinant pB22 indicate that the product of gene tolC, but not that of tonB, is required for the expression of the PacB and Ter phenotypes.

Biological Transport↗
PubMed1996

Purification and cDNA cloning of SAPKK3, the major activator of RK/p38 in stress- and cytokine-stimulated monocytes and epithelial cells.

Two chromatographically distinct stress-activated protein kinase kinases (SAPKKs) have been identified in several mammalian cells, termed SAPKK2 and SAPKK3, which activate the MAP kinase family member RK/p38 but not JNK/SAPK in vitro. Here we demonstrate that SAPKK2 is identical or very closely related to the MAP kinase kinase family member MKK3. However, under our assay conditions, SAPKK3 was the major activator of RK/p38 detected in extracts prepared from stress- or interleukin-1-stimulated epithelial (KB) cells, from bacterial lipopolysaccharide and tumour necrosis factor alpha-stimulated THP1 monocytes or from rabbit skeletal muscle. The activated form of SAPKK3 was purified from muscle to near homogeneity, and tryptic peptide sequences were used to clone human and murine cDNAs encoding this enzyme. Human SAPKK3 comprised 334 amino acids and was 78% identical to MKK3. The murine and human SAPKK3 were 97% identical in their amino acid sequences. We also cloned a different murine cDNA that appears to encode a SAPKK3 protein truncated at the N-terminus. SAPKK3 is identical to the recently cloned MKK6.

Amino Acid Sequence↗
PubMed1996

The Src SH3 domain is required for DNA synthesis induced by platelet-derived growth factor and epidermal growth factor.

The Src family of protein tyrosine kinases has been implicated in the response of cells to platelet-derived growth factor (PDGF) or epidermal growth factor (EGF). We recently described a microinjection approach that we used to demonstrate that kinase activity of Src family members is required for PDGF- and EGF-induced S-phase entry of fibroblasts. We have now used this approach to ask whether a functional SH3 domain of Src is required to transduce the mitogenic signal upon PDGF or EGF stimulation. Microinjection of plasmids encoding Src mutants lacking the SH3 domain (SrcDeltaSH3) or point-mutated within the ligand binding surface of the SH3 domain, but with intact kinase domains, inhibited the mitogenic effect of PDGF and EGF in fibroblasts. SrcDeltaSH3 could still associate with the PDGF receptor, suggesting that the inhibitory effect of the Src SH3 mutants was brought about by a failure of the PDGF receptor.SrcDeltaSH3 complex to relay the mitogenic signal further downstream. Chimeric molecules in which the Src SH3 domain was replaced with that of spectrin or Lck also blocked PDGF-induced DNA synthesis, whereas a chimera containing the Fyn SH3 domain did not. These data suggest that the Src or Fyn SH3 domain is required either for correct substrate selection or to recruit other proteins to the PDGF receptor.

3T3 Cells↗
PubMed1996

Survival and regeneration of neurons of the supraoptic nucleus following surgical transection of neurohypophysial axons depend on the existence of collateral projections of these neurons to the dorsolateral hypothalamus.

The aim of the present study was to compare the postlesional responses of vasopressin-producing (VP) and oxytocin-producing (OT) neurons of the supraoptic nucleus (SON) to transection of neurohypophysial axons. At different times after sectioning the median eminence of adult rats, immunocytochemical staining of both types of neuronal cell bodies and axons indicated that: (1) the number of OT neurons detected within the SON was only slightly decreased as compared with controls (-20%), whereas the number of VP neurons was severely decreased (-60%); and (2) the large majority of axonal sprouts that regenerated into the external layer of the median eminence were OT neurohypophysial axons. The injection of a retrograde tracer into various areas surrounding the SON further showed that numerous SON neurons could be retrogradely labeled when the injection was centered in the lateral hypothalamus dorsal to the SON. The immunocytochemical identification of these retrogradely labeled neurons demonstrated that most of them were OT neurons. When animals were subjected to median eminence transection and to a unilateral surgical cut placed in the lateral hypothalamus above the SON, the survival of both OT and VP neurons was dramatically reduced in the SON ipsilateral to the hypothalamic lesion, as compared to the contralateral SON. Taken together, these data indicate that OT (and to a lesser extent VP) neurons of the SON display collateral projections towards the lateral hypothalamus that protect them from retrograde degeneration following the lesion of their neurohypophysial projections.

Animals↗
PubMed1996

Aged median eminence glial cell cultures promote survival and neurite outgrowth of cocultured neurons.

We have recently shown that tanycytes, a particular type of glial cell that has morphological and biochemical similarities with radial glial cells, constitute a preferential support for the regeneration of lesioned neurohypophysial axons. The present study was designed to explore the possible neurotrophic role of tanycytes in vitro. Glial cells derived from the median eminence or from the cerebral cortex of 10-day-old rats were cultured for 4-7 weeks. At these times the majority of the cells identified in the median eminence cultures exhibited immunostaining patterns of tanycytes, as detected in the mediobasal hypothalamus of 10-day-old and adult rats, i.e., they were immunoreactive to vimentin (VIM), to DARPP-32 (a dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein), and to a lesser extent to glial fibrillary acidic protein (GFAP) antibodies. On the other hand, the majority of cells in cortex cultures showed immunostaining patterns of astrocytes, i.e., they were intensely immunoreactive to GFAP and VIM antibodies but negative to DARPP-32. Cells obtained from the dissociation of 3-day-old rat mesencephalon, cortex, and hypothalamus were cocultured on these glial monolayers, and the number of surviving neurons and their neurite length were quantified after 8 days. Our data showed that, when compared with astrocytes, tanycytes greatly improved both survival (six-to ten-fold higher) and neurite outgrowth (two- to five-fold longer) of cocultured neurons whatever their origin. Experiments performed by coculturing neurons on millicell inserts placed above the glial monolayers showed that diffusible factors from median eminence glial cells slightly increased survival (1.7-fold higher) of cocultured neurons but had no significant effect on neurite outgrowth. These observations indicate: 1) that aged tanycytes have a capacity to support survival and neurite outgrowth for a variety of postnatal neurons; and 2) that this neurotrophic effect is exerted mainly by means of specific molecules bound to the tanycytic plasmalemma limiting membrane and/or to the extracellular matrix.

Animals↗
PubMed1996

Immunocytochemical characterization of a new marker of fibrous and reactive astrocytes.

A specific monoclonal antiserum (Mab 6.17) inducing a strong immunostaining of the neuromuscular junction has been used to detect the possible occurrence of the corresponding antigen throughout the intact or lesioned central nervous system of adult rats. In intact animals, 6.17-immunolabeling was essentially detected in astrocyte-like structures located in white matter fasciculi of the brain, such as the optic tract, corpus callosum, fornix, and in the white matter of the spinal cord. The astroglial nature of such 6.17-immunolabeled profiles was verified by performing double or triple immunofluorescent labeling with Mab 6.17 and with specific antisera against astrocytic markers, such as S100 protein, glial fibrillary acidic protein and vimentin. In the white matter, all the structures reactive to Mab 6.17 were also reactive to antibodies against S100 protein, glial fibrillary acidic protein and vimentin. On the other hand, astrocytes of the grey matter that were immunoreactive to S100 and glial fibrillary acidic protein but negative to vimentin, were devoid of 6.17-immunoreactivity. After lesions including stab wound through the diencephalon or transection of the spinal cord, a marked increase of 6.17-immunostaining was noted in the regions surrounding the lesions. In these regions, 6.17-immunolabeling was associated with S100-, GFAP- and vimentin-positive astrocytes constituting the glial scar. The ultrastructural localization of 6.17-immunoreactivity indicated that, similar to glial fibrillary acidic protein and vimentin, the recognized antigen was mainly associated with gliofilaments. These observations indicate that, in the central nervous system of adult rats, Mab 6.17 recognizes a molecule associated with gliofilaments, which is essentially associated to reactive astrocytes expressing high levels of vimentin.

Animals↗
PubMed1996

Biphasic response of spinal GABAergic neurons after a lumbar rhizotomy in the adult rat.

The expression of gamma-aminobutyric acid (GABA) and of the isoforms of the enzyme involved in its synthesis, glutamic acid decarboxylase (GAD), is modified in several rat brain structures in different injury models. The aim of the present work was to determine whether such plasticity of the GABAergic system also occurred in the deafferented adult rat spinal cord, a model where a major reorganization of neural circuits takes place. GABAergic expression following unilateral dorsal rhizotomy was studied by means of non-radioactive in situ hybridization to detect GAD67 mRNA and by immunohistochemistry to detect GAD67 protein and GABA. Three days following rhizotomy the number of GAD67 mRNA-expressing neurons was decreased in the superficial layers of the deafferented horn, while GABA immunostaining of axonal fibres located in this region was highly increased. Seven days after lesion, on the other hand, many GAD67 mRNA-expression neurons were bilaterally detected in deep dorsal and ventral layers, this expression being correlated with the increased detection of GAD67 immunostained somata and with the reduction of GABA immunostaining of axons. GABA immunostaining was frequently found to be associated with reactive astrocytes that exhibited intense immunostaining for glial fibrillary acidic protein (GFAP) but remained GAD67 negative. These results indicate that degeneration of afferent terminals induces a biphasic response of GABAergic spinal neurons located in the dorsal horn and show that many spinal neurons located in deeper regions re-express GAD67, suggesting a possible participation of the local GABAergic system in the reorganization of disturbed spinal networks.

Animals↗
PubMed1995

Oxysterol (7 beta-hydroxycholesteryl-3-oleate) promotes serotonergic reinnervation in the lesioned rat spinal cord by reducing glial reaction.

In the present study, following previous experience with electrolytic lesion of the rat brain, and subsequent reduction of reactive gliosis with 7 beta-hydroxycholesterol derivatives (Bochelen et al.: Neuroscience 51:827-834, 1992), we have performed a hemisection of the spinal cord in adult rats and investigated the influence of 7 beta-hydroxycholesteryl-3-oleate (oxysterol) on the intensity of the astrocytic reaction and the axonal regeneration. We have shown here that local administration of liposomes containing this oxysterol reduced the intensity of the astroglial reaction on the sectioned side, as seen with immunocytochemical detection of glial fibrillary acidic protein (GFAP) and by in situ hybridization with a specific RNA probe. Moreover, radioautographic evaluation of astrocyte proliferation with tritiated thymidine evidenced a reduction of the astrocyte labelling index. In addition, double immunocytochemical detection of GFAP and polysialylated neural cell adhesion molecule (E-NCAM) revealed a decrease of the expression of this molecule in reactive astrocytes of the treated animals. Finally, immunocytochemical detection of serotonin (5HT) was determined in the raphespinal projections, which constitute a major descending system. In treated animals, serotonergic axons originating from the intact side reinnervated the dorsal horn of the sectioned side, below the hemisection. These results demonstrate that 7 beta-hydroxycholesteryl-3-oleate can reduce the astrocytic reaction following spinal cord injury, promoting the serotonergic reinnervation of a denervated territory.

Animals↗
PubMed1995

Transected axons of adult hypothalamo-neurohypophysial neurons regenerate along tanycytic processes.

In the intact hypothalamo-neurohypophysial system, oxytocinergic or vasopressinergic neurons project their axons throughout the internal layer of the median eminence towards the blood vessels of the hypophysial neural lobe. When transected at the level of the median eminence, these axons undergo massive sprouting towards the external layer of the organ and the underlying perivascular region containing hypophysial portal vessels. The present study was designed to explore the possible roles of median eminence glial cells in such a reorganization of transected neurohypophysial axons. The relationships between regenerating axons and glial cells were studied by laser scanning confocal microscopy and electron microscopy on vibratome sections immunostained with specific antibodies against neurohypophysial peptides and/or against glial markers. All along the intact median eminence, two main types of glial cells were identified: (1) tanycytes immunoreactive to vimentin and slightly immunoreactive to glial fibrillary acidic protein, and (2) classical astrocytes immunoreactive to glial fibrillary acidic protein but vimentin-negative. In the intact median eminence, neurohypophysial axons were associated with astrocytic processes located in the internal layer. After a lesion of the hypophysial stalk, peptidergic regenerating axonal sprouts were found to project massively towards the external layer and to penetrate the underlying perivascular region in close association with tanycytic-like processes immunoreactive to both vimentin and to glial fibrillary acidic protein. In contrast, regenerating sprouts were absent from those regions of the lesioned median eminence containing astrocytic processes immunoreactive to glial fibrillary acidic protein but vimentin-negative. When fixed lesioned median eminences were treated by placing crystals of the lipophilic dye DiI on their ventricular surface, regenerating axons were found to be closely associated with DiI-labelled tanycytic-like end feet terminating in the external layer, and with connected thin processes projecting through the external vascular region. These data indicate that in the median eminence of the adult rat, lesioned neurohypophysial axons regenerate in close association with tanycytic processes.

Animals↗
PubMed1995

Sequence requirements for binding of Src family tyrosine kinases to activated growth factor receptors.

Activation of growth factor receptor protein tyrosine kinases frequently results in the binding of numerous proteins to their tyrosine-phosphorylated cytoplasmic domains. These interactions involve the SH2 domains of the binding proteins and phosphorylated tyrosines on the receptor molecules, with the specificity of interaction dictated by the amino acid composition surrounding the phosphorylated tyrosine. In the case of the platelet-derived growth factor (PDGF) receptor, the major binding site for Src family tyrosine kinases is in the juxtamembrane domain and includes tyrosine 579 (Mori, S., Rönnstrand, L., Yokote, K., Engström, A., Courtneidge, S. A., Claesson-Welsh, L., and Heldin, C-H. (1993) EMBO J. 12, 2257-2264). To analyze in more detail which amino acids surrounding the phosphorylated tyrosine at position 579 were important for high affinity interaction with Src family kinases, we synthesized a series of phosphopeptides corresponding to this binding site in which single amino acids were individually changed and tested their ability to compete with the PDGF receptor for binding of Fyn. We found that not only the three residues carboxyl-terminal to the phosphorylated tyrosine were important but that also residues at positions -1 and +4 relative to the tyrosine were required. Phosphorylation of both tyrosines 579 and 581 significantly increased competition efficiency. The activated colony stimulating factor-1 (CSF-1) receptor, which is known to associate with Src family kinases, has a sequence in its juxtamembrane region similar to that surrounding Tyr-579 of the PDGF receptor, and a phosphopeptide modeled on this sequence competed the association of Fyn with the receptor in vitro. Furthermore, mutational analysis demonstrated that these sequences were required for the efficient association of Src family kinases with the activated CSF-1 receptor in vivo. Phosphopeptides corresponding to the Src family binding sites of both PDGF and CSF-1 receptors activated Src kinase activity in vitro. These observations support a model in which the enzymatic activity of Src family tyrosine kinases is controlled by intra- and intermolecular interactions of tyrosine-phosphorylated peptides with the SH2 domain of the kinases.

3T3 Cells↗
PubMed1995

Characterization and localization of the BM88 antigen in the developing and adult rat brain.

Monoclonal antibody BM88 identifies a neuron-specific antigen (BM88 antigen) present in the central and peripheral nervous system of the pig (Patsavoudi et al.: Neuroscience 30:463-478, 1989; J Neurochem 56:782-788, 1991). We have previously shown that the antigen is also expressed by cultured neurons derived from newborn rat brain. In the present study we have used the monoclonal antibody BM88 and a specific polyclonal antibody in order to identify the nature of the cross-reactive antigen in rat brain and to investigate its expression and cellular localization in the developing and adult rat nervous system. Western blot analysis and immunocytochemistry revealed that the rat BM88 antigen displays very similar biochemical properties with its porcine homologue. It is a neuron-specific integral membrane protein, apparently not glycosylated, consisting of two 23 kD polypeptide chains. Immunoperoxidase staining demonstrated that the BM88 antigen is widely distributed in the brain of 19-day-old rat embryos. At this stage, immunoreactivity was particularly prominent in differentiated cellular areas and developing fiber tracts of the embryonic rat brain, but was also present in the neuroepithelium. A similar wide distribution of the BM88 antigen was observed in the adult rat brain. Here, immunoreactivity was detected in the neuropil and neuronal perikarya. Immunocytochemical analysis of the expression of the BM88 antigen during postnatal development of the cerebellar cortex showed that this molecule is particularly concentrated in the Purkinje cells between postnatal days 10 to 15; their somata and developing dendrites were distinctly immunopositive during this period. An age-dependent increase in the expression of the BM88 antigen both in brain and in the cerebellum was noted. Electron microscopy confirmed the presence of the BM88 reaction product within the perikarya, axons and dendrites of labeled neurons in the adult brain. The BM88 reaction product was preferentially associated with the limiting membrane of mitochondria, endoplasmic reticulum and small electron-lucent vesicles, but was also present in the plasma membrane, especially at the level of synaptic densities. Our results show that the BM88 antigen participates in an activity common to all or most neurons, and demonstrate that the expression of this antigen is elevated upon neuronal differentiation and maturation.

Animals↗
PubMed1995

B-50 (GAP-43) immunoreactivity is rarely detected within intact catecholaminergic and serotonergic axons innervating the brain and spinal cord of the adult rat, but is associated with these axons following lesion.

The persistence of high levels of B-50 (GAP-43) in fibers innervating various regions of the adult central nervous system is generally thought to characterize neuronal systems capable of undergoing morphological plasticity. In a recent series of in situ hybridization studies, it has been shown that most catecholaminergic and serotonergic neurons of the adult rat brain express high levels of B-50 mRNA. The present study addresses the question whether high expression of B-50 mRNA in the catecholaminergic and serotonergic perikarya corresponds with detectable high levels of the B-50 protein in the efferent axonal fibers that innervate various regions of the adult rat brain and spinal cord. For this purpose, vibratome sections were doubly immunostained for B-50 and for tyrosine hydroxylase or serotonin and were analyzed by laser scanning confocal microscope. Colocalizations were investigated either (1) in regions of intact rat brain and spinal cord in which particular concentrations of B-50 immunoreactive fibers appeared codistributed with catecholaminergic or serotonergic fibers or (2) in intrahypothalamic portions of the medial forebrain bundle in which a surgical lesion was made. In the intact brain, frequent colocalizations of B-50 and tyrosine hydroxylase were detected in fibers innervating both the mediobasal hypothalamus and the neurointermediate hypophysial lobe. In all the other regions examined, the analysis of thin optical sections demonstrated that immunoreactivity to B-50 was only rarely associated with axonal profiles immunoreactive to tyrosine hydroxylase or to serotonin. By contrast, in the lesioned medial forebrain bundle B-50 immunoreactivity was found to be associated with numerous catecholaminergic and serotonergic axonal sprouts that regenerate around the surgical lesion. These data indicate that the majority of intact catecholaminergic and serotonergic axons innervating the adult rat brain and spinal cord contains low levels of B-50. However, following axotomy, B-50 is immunocytochemically detectable in the regenerating sprouts produced by both types of axonal fibers. This suggests that under basal conditions the relatively high content of B-50 mRNA in monoaminergic perikarya does not lead to appreciable accumulation of B-50 within corresponding axonal fibers and terminals, whereas conditions of morphological reorganization induce increased production of B-50 that accumulates within monoaminergic axonal sprouts.

Animals↗
PubMed1995

The influence of flavored solution concentration on the poisoned-partner effect.

Two experiments are reported in which we attempted to replicate the poisoned-partner effect, varying the concentration of a novel-tasting solution. Unpoisoned rats exhibited an aversion to a saccharin solution that had been consumed previously in the presence of a poisoned rat when it had a concentration of 0.6% but did not when it was of 0.15%. These results seem to show that the poisoned-partner effect depends upon the intensity of the solution employed and to suggest that it may be facilitated by a low initial consumption.

Animals↗
PubMed1995

Immunolocalization of B-50 (GAP-43) in intact and lesioned neurohypophysis of adult rats.

The persistence of high levels of B-50 in the adult brain is generally assumed to characterize neuronal systems capable of undergoing some form of plasticity such as axonal sprouting and regeneration. Since adult hypothalamo-neurohypophysial neurons are known to rapidly regenerate after being transected, the present study was undertaken to determine if such a capacity for regeneration could be related to the expression of this protein. Adult rats were killed by intraaortic perfusion of fixative either without lesion or at different delays after a surgical transection of the hypophysial stalk. Electron microscopy and laser scanning confocal microscopy were used to examine the regenerating axons after single or double immunocytochemical labeling of vibratome sections for B-50 and for various neuronal markers characterizing different types of neurohypophysial axons. In intact neurohypophysis, B-50 immunostaining was frequently associated with fibers immunoreactive to GABA or to tyrosine hydroxylase, whereas it was not detected within peptidergic neurohypophysial axons. In the lesioned neurohypophysis, B-50 was again frequently localized within axonal fibers immunoreactive to tyrosine hydroxylase or GABA. On the other hand, B-50 immunostaining was never detected within the numerous vasopressinergic or oxytocinergic axonal sprouts that regenerate all along the median eminence proximal to the lesion. These data indicate that persistence of high levels of B-50 within the neurohypophysis of adult rats is a specific feature of catecholaminergic and/or GABA-ergic axons innervating this region and that, contrasting to other neuronal systems, B-50 is not involved in the remarkable capacity for regeneration exhibited by the vasopressinergic and oxytocinergic neurohypophysial axons.

Animals↗
PubMed1995

Non-dopaminergic catecholaminergic neurons of mesencephalic and medullary nuclei contain different levels of dopamine.

The present study addresses the question whether metabolic dopamine can be immunocytochemically detected within non-dopaminergic catecholaminergic axonal fibers. For this purpose, confocal microscopy was used to analyze sections treated for the double fluorescence immunostaining of dopamine and either noradrenaline or phenylethanolamine-N- methyltransferase (the enzyme in adrenergic neurons that converts noradrenaline into adrenaline). Our data demonstrate that throughout the brain and spinal cord, the majority of the axonal fibers that reacted with the anti-phenylethanolamine-N-methyltransferase antibodies also exhibited faint to intense dopamine immunoreactivity. Similarly noradrenaline and dopamine immunoreactivities were frequently colocalized within axonal fibers innervating brain and spinal cord regions that receive a dense innervation from medullary noradrenergic neurons. On the contrary, dopamine was rarely detected within noradrenaline-immunoreactive fibers in those regions where the noradrenergic innervation essentially arises from noradrenergic neurons of the locus coeruleus. A similar differential dopamine immunostaining was observed in the corresponding neuronal perikarya of the medulla oblongata and the locus coeruleus. These data indicate that two types of non-dopaminergic catecholaminergic neurons can be distinguished according to their content in dopamine: (i) the noradrenergic and adrenergic neurons located in the medulla oblongata, whose cell bodies and axons contain high concentrations of metabolic dopamine and (ii) the noradrenergic neurons located in the mesencephalon, which contain low levels of metabolic dopamine.

Adrenergic Fibers↗
PubMed1995

[Factors associated with high grade dysplasia and cancer in colorectal adenoma].

The aim of this study was to assess the risk factors associated with high grade dysplasia (HGD) and cancer (CA) in colorectal polyps. We studied prospectively all colorectal polyps endoscopically resected from 6/91 to 12/93. Analyzed variables were age, sex and initial symptoms of patients, and number, localization, size and histologic characteristics of polyps. Adenomas were classified, according to the proportion of villous component, into tubular, villous A (1%-25% of villous component), villous B (26%-75%), villous C (76%-99%) and villous D 100%). One hundred polyps were resected from 67 patients (polyp/patient ratio:1.49). Mean age of patients was 63.9 +/- 10.3 year and 47 (70%) were men. Hematochezia was the main symptom (46%) and all of these patients had rectosigmoid polyps. Ninety three (93%) polyps were adenomas: Tubular 40 (43%), villous A 17 (18%), villous B 16 (17%), villous C 12 (13%) and villous D 8 (9%); 5 (5%) hyperplastic, 1 (1%) hammartoma and 1 (1%) inflammatory. Ten (11%) adenomas had foci of adenocarcinoma, 28 (30%) mild dysplasia, 42 (45%) moderate dysplasia and 20 (14%) high grade dysplasia. The percentage of villous C and D adenomas with cancer was 20% vs 3.6% of villous A adenomas (p: < 0.05) and 0% of villous B adenomas (p: < 0.-01). The percentage of villous C and D adenomas with HGD was 40% vs 10.7% of villous A adenomas (p: < 0.01%) and 6% of villous B adenomas (p: < 0.02). Mean size was 1.78 +/- 0.6 cm in adenomas with HGD and 1.28 +/- 0.7 cm in adenomas without HGD (NS). We didn't observe complications of the polipectomy. We conclude that colorectal polyps prevail in men with a 2:1 relationship. Patients who referred hematochezia as presenting symptom, had rectosigmoid polyps. High grade dysplasia and cancer were associated with the proportion of villous component but not with polyp's size or patient's age or sex.

Adenoma↗