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F de Castro

Publications and source records attributed to F de Castro.

At least 19 recordsLinked to original sources
PubMed2002

The olfactory bulb as an independent developmental domain.

The olfactory system is a good model to study the mechanisms underlying guidance of growing axons to their appropriate targets. The formation of the olfactory bulb involves differentiation of several populations of cells and the initiation of the central projections, all under the temporal and spatial patterns of gene expression. Moreover, the nature of interactions between the olfactory epithelium, olfactory bulb and olfactory cortex at early developmental stages is currently of great interest. To explore these questions more fully, the present review aims to correlate recent data from different developmental studies, to gain insight into the mechanisms involved in the specification and development of the olfactory system. From our studies in the pax6 mutant mice (Sey(Neu)/Sey(Neu)), it was concluded that the initial establishment of the olfactory bulb central projections is able to proceed independently of the olfactory sensory axons from the olfactory epithelium. The challenge that now remains is to consider the validity of the olfactory bulb as an independent development domain. In the course of evaluating these ideas, we will review the orchestra of molecular cues involved in the formation of the projection from the OB to the olfactory cortex.

Animals↗
PubMed2000

Evidence for intrinsic development of olfactory structures in Pax-6 mutant mice.

It has been reported that the arrival of primary olfactory axons is required to induce the development of the olfactory bulb (OB). On the other hand, the Sey(Neu)/Sey(Neu) mutant mouse (Small eye) has been previously described as a model for the absence of olfactory bulbs, owing to the lack of olfactory epithelium (OE). In the present report, we take advantage of this mutant and study a neural structure in the rostral pole of the telencephalon that phenotypically resembles the prospective OB. We named this formation olfactory bulb-like structure (OBLS). We also report the occurrence, in the mutants, of small epithelial vesicles in the malformed craneofacial pits, resembling an atrophic OE, although a mature olfactory nerve was not identified. Axonal tracing, birthdating, immunohistochemistry, and in situ hybridization using antibodies and probes expressed in the olfactory system, indicated that two distinct structures observed in the OBLS correspond to the main and accessory olfactory bulbs of the control mouse. We propose that the OBLS has developed independently of the external influences exerted by the olfactory nerve. The presence of a prospective OB in the mutants, without intervening olfactory fibers, suggests that intrinsic factors could define brain territories even in absence of the proper afferent innervation. The intrinsic mechanisms and environmental cues in the telencephalon could be sufficient to promote axonogenesis in the projection neurons of the OB and guide their axons in a lateral prospective tract, in the absence of olfactory axons.

Animals↗
PubMed1999

Chemoattraction and chemorepulsion of olfactory bulb axons by different secreted semaphorins.

During development, growth cones can be guided at a distance by diffusible factors, which are attractants and/or repellents. The semaphorins are the largest family of repulsive axon guidance molecules. Secreted semaphorins bind neuropilin receptors and repel sensory, sympathetic, motor, and forebrain axons. We found that in rat embryos, the olfactory epithelium releases a diffusible factor that repels olfactory bulb axons. In addition, Sema A and Sema IV, but not Sema III, Sema E, or Sema H, are able to orient in vitro the growth of olfactory bulb axons; Sema IV has a strong repulsive action, whereas Sema A appears to attract those axons. The expression patterns of sema A and sema IV in the developing olfactory system confirm that they may play a cooperative role in the formation of the lateral olfactory tract. This also represents a further evidence for a chemoattractive function of secreted semaphorins.

Animals↗
PubMed1999

Cloning, expression, and genetic mapping of Sema W, a member of the semaphorin family.

The semaphorins comprise a large family of membrane-bound and secreted proteins, some of which have been shown to function in axon guidance. We have cloned a transmembrane semaphorin, Sema W, that belongs to the class IV subgroup of the semaphorin family. The mouse and rat forms of Sema W show 97% amino acid sequence identity with each other, and each shows about 91% identity with the human form. The gene for Sema W is divided into 15 exons, up to 4 of which are absent in the human cDNAs that we sequenced. Unlike many other semaphorins, Sema W is expressed at low levels in the developing embryo but was found to be expressed at high levels in the adult central nervous system and lung. Functional studies with purified membrane fractions from COS7 cells transfected with a Sema W expression plasmid showed that Sema W has growth-cone collapse activity against retinal ganglion-cell axons, indicating that vertebrate transmembrane semaphorins, like secreted semaphorins, can collapse growth cones. Genetic mapping of human SEMAW with human/hamster radiation hybrids localized the gene to chromosome 2p13. Genetic mapping of mouse Semaw with mouse/hamster radiation hybrids localized the gene to chromosome 6, and physical mapping placed the gene on bacteria artificial chromosomes carrying microsatellite markers D6Mit70 and D6Mit189. This localization places Semaw within the locus for motor neuron degeneration 2, making it an attractive candidate gene for this disease.

Amino Acid Sequence↗
PubMed1999

Cloning and characterization of a novel class VI semaphorin, semaphorin Y.

Semaphorins comprise a large family of proteins implicated in axonal guidance. We cloned a novel transmembrane semaphorin, semaphorin Y (Sema Y), which has a class VI sema domain. Sema Y shows growth cone collapsing activity on DRG neurons in vitro, and the target regions of the DRG neurons express sema Y mRNA during development. Sema Y may be a stop signal for these neurons in their target areas. Interestingly, sema Y mRNA was also detected in other neurons and their targets. Two isoforms of Sema Y derived from alternative splicing were identified and their expression was found to be regulated in a tissue- and age-dependent manner. Distribution of sema Y mRNA suggests that Sema Y might also be important during maintenance of axonal connections and/or differentiation and migration of cells. Sequence comparison among class VI semaphorins revealed two short conserved sequence stretches in their cytoplasmic domains, suggesting interaction of these semaphorins with a common intracellular component(s).

Alternative Splicing↗
PubMed1998

Corneal innervation and sensitivity to noxious stimuli in trkA knockout mice.

Most primary sensory neurones depend on neurotrophins for survival. Mutant mice in which TrkA, the high-affinity receptor for nerve growth factor (NGF), has been inactivated lack nociceptive neurones in sensory ganglia and do not respond to noxious stimuli. The cornea of the eye is innervated by trigeminal neurones that are activated by noxious mechanical, thermal and chemical stimuli. In the human cornea, these stimuli evoke only sensations of pain. We have analysed the innervation pattern and the response to noxious stimulation of the cornea of trkA (-/-) mutant mice. Corneal nerves were stained with the gold chloride impregnation method. Corneal sensitivity to noxious stimuli was assessed by counting blinking movements evoked by von Frey hairs, topical application of saline at different temperatures and application of acetic acid and capsaicin at different concentrations. In the cornea of trkA (-/-) mutant animals, we observed a drastic reduction in the number of nerve trunks and branches in the corneal stroma. Furthermore, quantitative analysis of the number of thin nerve terminals revealed a marked decrease in the corneal epithelium of trkA (-/-) mice when compared to those present in wild type and trkA (+/-) animals. The blinking response of trkA (-/-) mice to mechanical, thermal and chemical noxious stimuli was also significantly reduced. These results indicate that the population of corneal sensory neurones is markedly depleted in trkA (-/-) mutant mice. However, a small portion of corneal sensory neurones survive in these mice suggesting that they may be NGF independent. On the basis of our results, we propose that these surviving cells are polymodal nociceptive neurones, sensitive to mechanical stimulation, noxious heat and acid.

Acids↗
PubMed1998

Semaphorins III and IV repel hippocampal axons via two distinct receptors.

The semaphorins are the largest family of repulsive axon guidance molecules. Secreted semaphorins bind neuropilin receptors and repel sensory, sympathetic and motor axons. Here we show that CA1, CA3 and dentate gyrus axons from E15-E17 mouse embryo explants are selectively repelled by entorhinal cortex and neocortex. The secreted semaphorins Sema III and Sema IV and their receptors Neuropilin-1 and -2 are expressed in the hippocampal formation during appropriate stages. Sema III and Sema IV strongly repel CA1, CA3 and dentate gyrus axons; entorhinal axons are only repelled by Sema III. An antibody against Neuropilin-1 blocks the repulsive action of Sema III and the entorhinal cortex, but has no effect on Sema IV-induced repulsion. Thus, chemorepulsion plays a role in axon guidance in the hippocampus, secreted semaphorins are likely to be responsible for this action, and the same axons can be repelled by two distinct semaphorins via two different receptors.

Animals↗
PubMed1996

Solitary sclerotic fibroma of the skin: a sclerotic dermatofibroma?

Two cases of solitary tumors showing well-demarcated hypocellular, dermal fibrocollagenous proliferations are reported. The lesions were composed of hyalinized eosinophilic collagen bundles arranged in the characteristic interwoven pattern with prominent clefts, as described in sclerotic fibroma of the skin. This pattern, although predominant, was not uniform. Some areas showed a more cellular pattern with histopathologic features suggestive of dermatofibroma. In those areas, multiple spindle-shaped cells and occasional multinucleated cells were observed. The collagen bundles did not adopt a whorled pattern, and the overlying epidermis showed mild acanthosis and elongation of the rete ridges. The sclerotic changes were present mainly at the periphery and in the deep areas of the tumor. Our observations confirm the possibility that solitary sclerotic fibroma of the skin may represent, at least in some instances, the later and sclerotic stage of other more cellular neoplasms (specifically dermatofibromas) rather than an individualized neoplasm, as has been recently proposed.

Adult↗
PubMed1993

Inhibitory effect of high energy shock waves and radiotherapy in vitro.

Exposure of mice fibroblasts cell strain 3T3 to high energy shock waves and megavoltage radiotherapy resulted in a reduction in cell viability as determined by trypan-blue exclusion and H3-Thymidine incorporation assays. Electromagnetic shock waves have a higher cytotoxic effect on cell viability than megavoltage radiotherapy, at low and medium levels of energy. Megavoltage radiotherapy has a higher cytotoxic effect on cell viability at high levels of energy, as nucleoside incorporation reveals. The combination of electromagnetic shock waves and megavoltage radiotherapy delivered on cell cultures at medium levels of energy, did not enhance their cytotoxicity when it was compared with their high levels of energy individually.

3T3 Cells↗
PubMed1993

[Diagnosis of cancer of the prostate by determining the blood levels of specific prostatic antigen, rectal examination, and transrectal echography].

The usefulness of Prostate Specific Antigen (PSA), tactile rectal examination (TRE) and transrectal ultrasound (TRU) for the diagnosis of prostate cancer (PCa) was studied in 114 patients who came in for an evaluation of their mictional symptoms. Patients underwent random ultrasound-guided transrectal biopsies following findings of abnormal TRE and/or serum PSA concentrations > 5 ng/ml. Of the total series, 71% presented TRE abnormalities and 52% presented hypoechoic areas in the TRU (only ones to be considered suspicious). Also, 26%, 23% and 51% of patients presented normal (0-5 ng/ml), intermediate (5-10 ng/ml), and high (> 10 ng/ml) concentrations of serum PSA. Incidence of PCa was 31%. Based on the individual tests, both positive and negative predictive values were higher for serum PSA concentrations > 10 ng/ml. By combining the tests results, the diagnosis percentage was also higher with PSA levels > 10 ng/ml. Positive predictive value was 81% in patients with all three tests positive, 73% with suspicious TRE and high PSA and 70% with suspicious TRU and high PSA. Our results corroborate the superiority and efficacy of random biopsies over selective biopsies of hyperechoic areas. Nevertheless, of 21 patients with negative prostate biopsies who underwent TUR or retropubical adenomectomy, 28% had PCa. These findings indicate that random biopsies are associated with a percentage of false negatives which varies depending on the features of the sample being studied. In conclusion, PSA is the ideal complement to TRE, and the association of these two tests constitutes the best indication for an ultrasound-guided random prostate biopsy, with independence of any TRU findings.

Aged↗
PubMed1993

[Primary adrenal carcinoma].

A series of 17 patients with primary adrenal cortical carcinoma is presented. Of 14 patients without evidence of disseminated disease prior to radical surgery, 6 developed distant metastases during follow-up. The mean interval free of disease in these patients was 12 months (range 3-40) and the median survival 15 months. Of the six patients in whom adjuvant external beam radiotherapy was delivered, no evidence of local recurrence was observed. Of the patients treated without external beam radiotherapy, 3 local failures were observed. The projected 5 years survival was 35%, which is similar to that reported in the literature. To date, there is no evidence that chemotherapy nor radiotherapy could improve the survival, however, radiotherapy might increase the local control in selected cases.

Adrenal Cortex Neoplasms↗
PubMed1992

[Monotherapy of ureteral calculi with extracorporeal shockwave lithotripsy].

We reviewed our experience with ESWL in the treatment of 401 patients with ureteral stones in order to evaluate if a higher disintegration and clearance rates could be achieved without prior manipulation of ureteral calculi, i.e., ESWL used as "in situ" monotherapy. The global stone free rate were 83%, 85% and 91% at 15 days, 1 month and 3 months after ESWL. We also analyzed the results according to the efficiency quotient (EQ).

Adolescent↗
PubMed1992

[Vascular complications in 237 recipients of renal transplant from cadaver].

Between July 1976 and June 1990, 244 transplantations were performed. Of the 237 patients monitored, 13 (5.4%) had vascular complications: 10 (77%) renal artery stenosis, 1 (7.7%) primitive iliac artery stenosis, 1(7.7%) renal artery thrombosis, 1 (7.7%) renal vein thrombosis. Six patients underwent surgery (Angioplasty was performed in three patients, re-anastomosis to the common iliac artery in one, by-pass of saphenous vein in another one, while in the last one it was tried a release of the vascular pediculus). Management with drugs was possible in one case. At present, 11 of the 13 patients are still alive and three of the grafts remain functional after a mean follow-up time of 83 months. According to a univariate study, the influential factors in the development of vascular complications are, the identity of Locus A, the type of extraction in Locus B, the length of cold ischaemia, the type of vascular anastomosis and the number of previous rejections. The factors with maximal influence in the development of complications are the type of vascular suture (with or without patch) and the number of previous rejections (according to a study of log regression models). The study demonstrates the significant influence vascular complications have on the graft's durability (p = 0.005).

Cadaver↗
PubMed1992

[Prognostic value of local vascular infiltration in infiltrating transitional carcinoma of the bladder].

The present retrospective study analyzes the evolution and survival of 79 patients with bladder infiltrant transitional carcinoma (T2-T3), which were treated with radical cystectomy and bilateral ilio-obturating lymphadenectomy. Pre-operative radiotherapy (57/79) and neo-adjuvant chemotherapy (24/79) was used as supplementary therapy. The univariate analysis showed the relationship between tumour vascular infiltration (TVI) and presence of nodes micrometastasis (p = 0.002). The variables with greater forecast power in the multivariate analysis for survival were a decline in the post-radio and/or neo-adjuvant chemotherapy tumoral stage (p = 0.000) and TVI (p = 0.001). Survival decreased significantly in patients with TVI (p = 0.008), this finding denoting a worse prognosis than the presence of nodular micrometastasis (p = 0.01).

Actuarial Analysis↗
PubMed1991

Myxedema ascites. Report of two cases and review of the literature.

Ascites is a well-known but uncommon occurrence in hypothyroid patients. We describe two patients with clinical ascites that resolved completely on thyroid replacement therapy. Our review of the literature found 21 well-documented cases of myxedema ascites. Prominent features of this condition include a high protein content of the ascitic fluid (greater than 2.5 g/dl), a high albumin serum-ascites gradient, a long duration of the ascites, and its resolution on thyroid replacement. We also found a slight female predominance. The exact mechanisms responsible for ascites accumulation are unknown and some of the hypotheses are discussed. We conclude that ascites associated with hypothyroidism is rare but must be recognized early since thyroid replacement is definitive therapy.

Adult↗
PubMedDate not supplied

[Protocortex versus protomap: a perspective from the olfactory bulb].

INTRODUCTION AND AIM: The olfactory sensory system is a unique model for the research of guidance and connectivity of growing axons. During development, the olfactory epithelium, the olfactory bulb and the olfactory cortex differentiate several cell types and extend projection axons. Because there is a close relationship between these three structures, we ask the question as to whether establishment of the olfactory bulb central projections can proceed independently of the arrival of the olfactory sensory afferents. This raises another more general question: is establishment of afferent connections necessary to awake a developmental program in target cells?. DEVELOPMENT: The initial establishment of the olfactory bulb central projections occurs independently of the arrival of the olfactory axons from the olfactory epithelium, which reinforces the idea that cortical regions are already patterned before migration of newborn neurons, at least for the olfactory bulb and maybe for the entire brain. This implies a strict intrinsic molecular control of the distinct olfactory structures, independent one of each other. CONCLUSIONS: How then, do axonal projections find their correct way within the brain? Contact-mediated mechanisms and chemotropic molecules cooperate to fix their position in the telencephalon, prevent bulbar axons from invading structures other than the olfactory cortex and, at the same time, stimulate axonal branching in an orchestra of both, attractive/promoting and repulsive/inhibiting signals. At later stages, the mature appearance of the olfactory bulb will be completed and refined.

Animals↗