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C Bertolotto

Publications and source records attributed to C Bertolotto.

32 records · Page 2Linked to original sources

Inhibition of the phosphatidylinositol 3-kinase/p70(S6)-kinase pathway induces B16 melanoma cell differentiation.

alpha-Melanocyte-stimulating hormone and cAMP-elevating agents are known to induce B16 cell differentiation, characterized by increased melanin synthesis and dendrite outgrowth. In order to elucidate intracellular signaling pathways involved in this differentiation process, we focused our interest on the phosphatidylinositol 3-kinase/p70(S6)-kinase pathway. The specific inhibition of phosphatidylinositol 3-kinase by LY294002 markedly stimulated dendrite outgrowth, thus mimicking the action of cAMP-elevating agents on B16 cell morphology. In addition, LY294002 and rapamycin, a specific p70(S6)-kinase inhibitor, were found to independently stimulate tyrosinase expression, thus increasing melanin synthesis. In an attempt to better dissect the molecular mechanisms triggered by cAMP to induce melanoma cell differentiation, we examined the effects of a cAMP-elevating agent forskolin, on both phosphatidylinositol 3-kinase and p70(S6)-kinase activities. Specific kinase assays revealed that forskolin partially inhibited phosphatidylinositol 3-kinase activity and completely blocked p70(S6)-kinase activity and phosphorylation. In conclusion, our results clearly demonstrate that the inhibition of phosphatidylinositol 3-kinase and p70(S6)-kinase is involved in the regulation of B16 cell differentiation. Furthermore, we provide evidence which suggests that cAMP-induced melanogenesis and dendricity are, at least partially, mediated by the cAMP inhibition of the phosphatidylinositol 3-kinase/p70(S6)-kinase signaling pathway.

Animals↗

Age-related changes in soma size of neurons in the spinal cord motor column of the cat.

The present study was undertaken to examine the effect of the aging process on the soma size and number of motoneurons and interneurons in the motor column of the spinal cord of old cats. Neurons in the motor column were divided into small and large populations based on a bimodal distribution of their soma cross-sectional areas. A 17% decrease in the cross-sectional area of small neurons was observed, this decrease was statistically significant (P < 0.0001). The cross-sectional area of large neurons decreased by only 6%, which was statistically significant (P < 0.05). On the other hand, there was no significant difference in the number of large, small or of these combined population of ventral horn neurons in the aged cats compared with the control animals. This data suggest that neurons in the motor column are not uniformly affected by the aging process because morphological changes are proportionally greater in small neurons than in large neurons.

Aging↗

Regulation of tyrosinase gene expression by cAMP in B16 melanoma cells involves two CATGTG motifs surrounding the TATA box: implication of the microphthalmia gene product.

In melanocytes and in melanoma cells, upregulation of melanogenesis, by cAMP elevating agents, results from a stimulation of tyrosinase activity that has been ascribed to an increase in tyrosinase protein and messenger amount. However, the mechanism by which cAMP elevating agents increase tyrosinase mRNA remains to be elucidated. In this study, using a luciferase reporter plasmid containing the 2.2-kb fragment 5' of the transcriptional start site of the mouse tyrosinase gene, we showed that cAMP elevating agents lead to a strong stimulation (20-fold) of transcriptional activity of the tyrosinase promoter. Deletions and mutations in the mouse tyrosinase promoter showed that the M-box 70-bp upstream from the TATA-box and the E-box located downstream the TATA-box, near to the initiator site, are involved in the regulation of the tyrosinase promoter activity by cAMP. Additionally, we showed that microphthalmia, a b-HLH transcription factor associated with pigmentation disorders in mouse, binds to these regulatory elements and modulates the transcriptional activity of the tyrosinase promoter. Since cAMP stimulates the binding of microphthalmia to the M-box and to the E-box; it is tempting to propose that microphthalmia, through its interaction with cis-acting elements surrounding the TATA-box, plays a key role in the regulation of the mouse tyrosinase gene expression by cAMP.

3T3 Cells↗

Morphological gradients in sensory hair cells of the amphibian papilla of the frog, Rana pipiens pipiens.

The sensory hair cells of the amphibian papilla (AP) of the northern leopard frog were examined in a light-microscopic analysis. Hair cell length and cross-sectional area were found to vary systematically along the rostro-caudal axis of the endorgan. The AP was readily divided into three morphological regions. Rostrally-located hair cells are tall, cylindrically-shaped cells with large cross-sectional areas and long stereocilia; caudally-located hair cells are short, goblet-shaped cells with small cross-sectional areas and short stereocilia. In the middle region, hair cells exhibit features intermediate to those of hair cells located at the AP extremes. The detailed pattern of changes in hair cell morphology along the endorgan correlates well with its observed tonotopy and may have implications for the intrinsic tuning of the AP.

Animals↗

Innervation of the amphibian and basilar papillae in the leopard frog: reconstructions of single labeled fibers.

Amphibians have two auditory organs specialized for reception of airborne sounds: the amphibian papilla and the basilar papilla. In this report we examine the morphology of the ganglion cells and the afferent innervation of the sensory epithelium in both auditory organs of the leopard frog, Rana pipiens pipiens. Extracellular injections of either biocytin or horseradish peroxidase (HRP) were made into the VIII nerve; they labeled ganglion cells, their axons, and their terminal fibers within the papillae. Ganglion cells that projected to either the amphibian papilla or basilar papilla had cell bodies that were morphologically distinct from other labeled cells. In the amphibian papilla thick fibers terminated in the rostral portion and thin fibers terminated in the caudal portion. Labeled fibers in the rostral portion traveled short distances before making contacts with up to nine hair cells whereas labeled fibers in the caudal portion traveled longer distances and contacted no more than five hair cells. In the basilar papilla labeled fibers were thick (around 4 microns) and terminated on as many as nine hair cells. Consistent with studies from the bullfrog, Rana catesbeiana, our results suggest that the amphibian papilla of R. pipiens pipiens has a convergent innervation (i.e., multiple hair cells provide input to a single ganglion cell) and is topographically organized. However, in contrast to reports in other ranid species, a highly convergent innervation like that found in the amphibian papilla is also found in the basilar papilla.

Animals↗

[The first isolation of Torulopsis glabrata (Anderson) Lodder from dental granulomas].

Three Torulopsis have been isolated from two hundred or so dental granulomas. Torulopsis glabrata has been observed in cases of ophthalmopathy, infections of the oral cavity, lung infections, endocarditis and septicaemia. Apical lesions due to Torulopsis glabrata are not typical of mycosis but are generic of dental granulomas. The histological granulomatous character prevails. Experimental infections have been obtained from this fungus. Human infections by Torulopsis glabrata have been described. These infections are induced particularly in subjects with their immunity systems depressed by prolonged cortisone therapy. Their systematic position and morphology in optical microscopy have been examined in accordance with current views.

Adult↗

[The first isolation of Cladosporium cladosporioides (Fres.) de Vries from dental granulomas].

Thirteen Cladosporium have been isolated from 221 dental granulomas. Cases have been observed of cerebral lesions both in man and cats. Also various types of lesions, encapsulated abscesses, etc. to be classified under the group of pheoifomycoses. Cutaneous allergies and cases of keratitis and chromoblastomycosis have been observed, too Cladosporium cladosporioides is very resistant to mercuric and phenolic compounds and radiations. The systematic position and morphology of Cladosporium have been fully examined in accordance to the latest scientific views.

Adolescent↗

A search for a mesencephalic periaqueductal gray-cochlear nucleus connection.

Horseradish peroxidase placed into the ventral mesencephalic periaqueductal gray (PAG) and in the lateral superior olivary complex region demonstrated indirect paths towards the cochlear nucleus (CN). Because no direct connections could be observed, a pathway throughout the auditory efferent system was proposed. The results suggest three possibilities: 1) The PAG is connected to the lateral superior peri-olivary complex synapsing with known efferent fibers that reach the CN; 2) Neurons located at the dorsal PAG were demonstrated to be connected to the inferior colliculus (IC). The possibility of synapses with known neurons that run from IC to the CN is postulated; 3) Neurons in the trapezoid body, which are partially associated with a system that communicates with the CN, are also connected to and from the PAG. The present results anatomically support an extracellular study (1) describing PAG actions on CN units.

Animals↗

Some aspects of the structural organization of the spinal cord of Gymnotus carapo (Teleostei, Gymnotiformes). I. The electromotor neurons.

The spinal electromotor neurons (EMNs) of Gymnotus carapo from a distinct column dorsal to the central canal. When massively retrograde-labeled with horseradish peroxidase, these neurons show a well-developed dendritic arborization. Dendrites run along the longitudinal axis of the cord and also project toward the dorsal gray and dorsolateral funiculi. Input to the EMNs is mediated by scarce synaptic contacts which show the fine structural characteristics of the so-called "morphologically mixed" junctions. Serial section reconstructions of the junctional areas revealed the occurrence of "gap junctions," dense membranes facing cumuli of microvesicles, and relatively large zones of undifferentiated membranes. Comparative electrophysiological and morphological data suggest that EMN activity may be mediated by electrical transmission. Since neither dendro-dendritic nor dendro-somatic junctions have been observed, other circuitry alternatives are proposed to account for the expected synchronized firing of the EMNs.

Animals↗