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Biomedical subjects

M J Muñoz

Publications and source records attributed to M J Muñoz.

At least 19 recordsLinked to original sources

Study and culture of haematopoietic progenitor cells from peripheral blood in rats, hamsters and mice.

The aim of this work was to isolate and cultivate a subpopulation of pluripotent stem cells present in peripheral blood of different animal species, frequently used in laboratory studies (mice, rats and hamsters). Pluripotent stem cells (PSCs), already described in human beings, are fibroblast-like cells that exhibit a CD34 marker, specific for haematopoietic stem cells. Commonly used human commercial media were investigated for culturing animal PSCs. These findings suggest that this simple and standardized methodology may be applicable in several fields such as the study of the pharmacological effects of drugs on the haematopoietic line and the study of new strategies in cellular therapy for some human diseases.

Animals↗

Use of nonlinear mixed effect modeling for the intestinal absorption data: application to ritonavir in the rat.

The aim of this study is to investigate in situ the mechanisms involved in the gastrointestinal absorption of ritonavir in the rat, as an animal model for preclinical studies of anti-HIV agents in vivo. Four ritonavir solutions (40, 27, 13 and 7 microM) in the presence of 1% dimethylsulfoxide (DMSO) were perfused in the small intestine of anaesthetised rats. Effects of DMSO on the intestinal permeability were investigated using solutions containing antipyrine 1.33 mM and ritonavir 7 microM with and without 1% of DMSO. Antipyrine and ritonavir transport was not modified in the presence of 1% of DMSO. The population pharmacokinetic parameters of the ritonavir intestinal transport were obtained by means of nonlinear mixed effect modelling approach according to a nonlinear absorption and nonlinear secretion. The absorption and secretion kinetic parameters for ritonavir were: Vm=47.6 microM/h; Km=8.77 microM; Vms=3.66 microM/h and Kms=0 microM. The interindividual variability found to ritonavir Vm 13.1%, and the residual variability was 8.98%. The Kms value support the saturation of the carrier at the range of concentrations of ritonavir assayed. The interindividual variability value of the Vm could explain, at least in part, the variability in absorption rate constants observed.

Animals↗

[Brainstem gliomas].

Brainstem gliomas have been increasingly understood in the last two decades and they are nowadays regarded as an heterogeneous group of tumors with tendency towards the pediatric age, where they account for 10-20% of brain neoplasms. Besides the well known diffuse tumor, several subtypes, with a different biological behaviour, amenable to surgical resection and better prognosis, have been identified, giving rise to many classifications and terms. In the other way, attention has been recently paid to adult brainstem gliomas in contrast to pediatric tumors. Based on a review of the literature, we describe the different subtypes of brainstem gliomas, with particular interest on therapeutic approaches and differences between pediatric and adult tumors, employing iconography from our series.

Adult↗

Conservation of purified protein derivative RT-23 tuberculin.

OBJECTIVE: Recommendations that purified protein derivative (PPD) RT-23 tuberculin should not be kept and used more than 24 to 48 hours after opening are rarely complied with. The aim of this study was to determine whether using PPD RT-23 tuberculin from vials that had been open for a longer time could affect results of tuberculin tests and whether the solution could become contaminated. METHODS: A prospective cross-sectional study was carried out. Two tuberculin tests were simultaneously administered, one in each forearm, to adult contacts of patients with active tuberculosis, one test using a recently opened vial of tuberculin (control) and the other using tuberculin that had been opened a week before (first phase) or a month before (second phase) (study tuberculin). Leftover tuberculin from several of the vials was cultured. RESULTS: For the 127 patients in the first group (tuberculin opened 1 week), the mean (SD) diameter of the induration was 6.2 (6.9) mm for the study tuberculin and 6.3 (6.9) mm for the control (P=.3). For the 83 patients in the second group (tuberculin opened 1 month), the mean diameter of the induration was 5.5 (7.3) mm for the study tuberculin and 5.7 (7.3) mm for the control (P=.5). There were no differences between the number of positive tests found. None of the cultured tuberculins produced bacterial growth. CONCLUSIONS: PPD RT-23 tuberculin does not appear to lose potency or sterility when vials have been opened for a week or a month.

Adolescent↗

Fronto-orbital remodeling without orbito-naso-frontal bandeau.

INTRODUCTION: Fronto-orbital bilateral advance is the procedure of choice for the treatment of craniosynostosis affecting most of the anterior area of the skull and orbitomalar regions. The aim of the technique is to achieve a supra-orbital bilateral bar and a frontal bone. We have introduced a modification in order to simplify the technique. PATIENTS AND METHODS: From November 1998 to January 2002, 18 patients with craniosynostosis have been surgically treated using our technique. The mean age when the treatment was performed was 6.93 months (range 3 to 22 months). Brain computed tomography (CT) scans and three-dimensional (3-D) reconstruction of CT scans were performed before and after treatment. SURGICAL TECHNIQUE: A bifrontal craniotomy was performed taking the osteotomy up to the supraorbital rim. A new frontal bone was obtained from another region of the cranium creating new orbital edges. The osteosynthesis was conducted using absorbable materials. RESULTS: The follow-up of the patients ranged from 3 months to 3 years. All patients were studied using CT scans and 3-D reconstruction of CT after treatment, which demonstrated the persistence of the fronto-orbital advance. No secondary complications related to the new technique were found in any of the patients. CONCLUSIONS: The frontal-orbital advance obtained was stable. The technique was simplified by not creating a supraorbital bar and by reducing the bone fixation points. The manipulation of both frontal lobes and orbital globes was negligible. The aesthetic results were excellent.

Bone Remodeling↗

[Congenital brain tumors: nine cases and review of the literature].

OBJECTIVE: To review congenital brain tumors patients younger than 2 months diagnosed in our Department. PATIENTS AND METHODS: Nine congenital brain tumors were diagnosed between 1983 and 2001 among a consecutive serie of 484 paediatric cerebral tumors (patients less than 15 years). Clinical and radiological findings and prognostic factors are analyzed. RESULTS: There were two teratomas, two glioblastomas, one xanthogranuloma affecting cavernous sinus, one supratentorial PNET and one medulloblastoma and one oligodendroglioma. In one case histological diagnosis was not possible. In four cases antenatal diagnosis was done by means of ultrasonography and MRI. Seven patients were operated on, with one intraoperative exitus. Five patients died due to tumoral progression in the first two months after surgery. Another case was considered not amenable for surgical resection, and thus was not operated. He died in the fifth day of life. Three patients are alive 14, 36 and 72 months after surgery, one with severe psicomotor delay, another one with normal mental status but dependent on seizures medication and the last one with mild mental delay. In the last case of our serie intrauterine death happened by 33(rd )week and histological diagnosis was not possible. CONCLUSIONS: Prognosis for congenital brain tumors depends on the operative morbidity and tumor histology. However final prognosis in these patients is still discouraging, despite early surgery and operative and anaesthetic improvements.

Adult↗

Intraventricular cavernoma in pediatric age.

INTRODUCTION: Cavernomas rarely occur in the ventricular system. Only 10 pediatric cases out of 46 well-documented cases have been published. CASE REPORT: We report the case of an 11-year-old girl operated on for a voluminous cavernoma at the ventricular trigone which was diagnosed after absence seizures. CONCLUSION: Interestingly, the case we report showed a hypointense rim on T2-weighted magnetic resonance images which has not been a common finding in the cases previously reported.

Cerebral Ventricle Neoplasms↗

Poly(A) site choice during mRNA 3'-end formation in the Schizosaccharomyces pombe wos2 gene.

In the fission yeast Schizosaccharomyces pombe, the wos2 gene encodes p23, a highly conserved protein which functions as a co-chaperone for the heat shock protein Hsp90. This p23 protein binds to Hsp90, but its activities and regulatory mechanisms are still unclear. Northern analysis has shown that the wos2 gene produces three transcripts of about 1.1, 0.9 and 0.8 kb, which are expressed differentially depending on the growth temperature. The largest and the smallest transcripts were most abundant at 25 degrees C, whereas the 0.9-kb transcript predominated at 37 degrees C. A time-course analysis indicated that this 0.9-kb species rapidly increased in abundance after a shift from 25 degrees C to 37 degrees C, reaching a maximum after 15 min. A shift back to 25 degrees C resulted in a decline in the amount of this transcript, albeit at a slower rate. Expression analysis of wos2:ura4 and nmt1:wos2 constructs showed that the 3' untranslated region of wos2 alone directs the formation of these multiple, discrete wos2 mRNAs. Sequence analysis of cDNAs derived from these mRNAs showed that the use of different polyadenylation sites results in the production of the three differently sized wos2 transcripts. In the case of the 0.9- and 0.8-kb mRNA species, these sites lie in a predicted hairpin loop in the mRNA, suggesting that polyadenylation signals in wos2 transcripts may be mediated by RNA secondary structure. The possibility that differential thermal stability of these hairpin structures could influence polyadenylation site choice during formation of the 3'-ends of the mRNAs is discussed.

3' Untranslated Regions↗

Surgical treatment of trigonocephalies and associated hypoteleorbitism.

Premature closure of metopic suture is a relatively uncommon form of craniosyostosis with an estimated incidence of 0,3 per 1000 live births, comprising about 7% of surgical craniosynostosis referred to craniofacial centers. A broad phenotypical spectrum spreads from minor metopic ridges to severe trigonocephaly with pterional indentation supraorbital bar retrusion, temporal and parietal compensating bossings and hypotelorism. Most of the cases arise spontaneously although autosomal dominant inheritance has been described and association with cromosomal abnormalities and different syndromes has been widely reported. Surgical correction has been attempted with good cosmetic results using several variations of the standard frontoorbitary advance. However there is still a number of questions to be solved in relation to this entity, mainly on its pathogenesis, but also on its development, natural history and treatment. Direct surgical approach to associated hypotelorism is a matter of argument when considering the reestablishment of normal interorbitary distances. We have conducted a retrospective analysis of our serie consisting of twenty-eight cases of trigonocephalies. Surgical correction of hypotelorism was attempted in eleven cases while the resting seven children remained "not treated". The objective was to review the functional outcome and cosmetic results comparing the different techniques applied to the frontal bone and to observe evolution of the hypoteleorbitism after the treatment with or without osteotomies and grafting of the nasoethmoidal area.

Child, Preschool↗

[Endoscopic treatment of suprasellar arachnoid cysts].

Arachnoid cysts account for only 1% of all intracranial space-occupying lesions. In adults suprasellar cysts represent 9% of all the arachnoid cysts while in pediatric population this percentage reaches 15%. In spite of being a problem relatively common in daily neurosurgical practice there are still a number of questions to be solved concerning pathogenesis and evolution, natural history and treatment. Located in the suprasellar cistern and closely related to the ventricular system, suprasellar arachnoid cysts conform a perfect indication for endoscopic treatment. The development and spreading of neuroendoscopic techniques have surpassed the standard microsurgical approaches as an elective treatment. However there is still controversy on the management of associated hydrocephalus, need for cystoperitoneal shunt after endoscopic fenestration or the superiority of ventriculocystocisternostomy over simple ventriculocystostomy. The authors present a serie of seven consecutive patients with "de novo" diagnosis of suprasellar arachnoid cyst. In every case the treatment consisted in endoscopic fenestration and removal of the cyst membranes, with or without associated ventriculostomy of the IIIrd ventricle. Preoperative symptoms improved in all the patients and five out of seven remain shunt free. One patient maintains a cystoperitoneal shunt and another one, previously shunted, remains shunt dependent. The clinical presentation and postoperative evolution are commented with discussion on the alternative therapeutic options from the endoscopic point of view.

Arachnoid Cysts↗

Spanish intercomparisons for individual monitoring.

The Spanish Nuclear Safety Council (CSN) carries out an intercomparison programme for individual monitoring every 5 years. The objective is to acquire valuable information on the performance of the dosimetry systems of the participating Spanish approved dosimetry services and to assess precision and accuracy as quality indicators of overall dosimetry performance. CSN has carried out two intercomparison programmes, the last one in 1995, in which 18 approved dosimetry services participated. The dosemeters were exposed to photon fields (137Cs gamma rays and two X ray beams of different qualities), at two standard laboratories in Spain. The irradiations were done for evaluating personal dose equivalent, Hp(10), using the ICRU 47 phantom. Presently, CSN is carrying out a new intercomparison, which will be finished in 2001. Twenty-three dosimetry services will participate; 22 from Spain and one from Cuba. The irradiations will be done in reference photon radiation fields.

Humans↗

The use of alternative systems for the ecotoxicological screening of complex mixtures on fish populations.

This paper presents the results of the use of alternative systems in a screening study of four complex mixtures. The following tests were performed: in vitro induction of micronuclei in a rainbow trout-derived cell line by flow cytometry, and hatching percentage, time of hatching and teratogenic alterations on the embryolarval development on medaka fish eggs. The results obtained with the proposed tests in this study allows an increase in the information level in a short period of time (2 weeks), using very low sample volumes (< 100 ml). Inclusion of chronic and specific effects (genotoxicity and teratogenicity) allows the selection of the most sensitive endpoint to increase security factors in the ecotoxicological assessment of complex mixtures, so that detailed studies can be focused only on those samples which require further research.

Animals↗

Ecotoxicological evaluation of pig slurry.

Swine sewage could be source of nutrients and pollutants. This work estimates the environmental risk in nine samples from different farm treatment systems based on the evaluation of their effects in Daphnia magna acute test, and on the assessment of Cu, Zn and ammonia as main contributors. NH3 and Cu were responsible for LC50 results (1-5% of dilution). Organic compounds were quantified through several extraction methods (SPMDs, SPE and solvent extraction). A more exhaustive extraction was performed in an additional sample, which showed indole and phenol recoveries much higher than the previous ones. This method also includes PCBs (430 ppb) and fatty acids (approximately =150 ppm) quantification.

Ammonia↗

[Neurocutaneous melanosis].

Neurocutaneous melanosis (NCM) is a rare congenital syndrome characterized by large or multiple congenital melanocytic nevi and excessive proliferation of melanotic cells in the leptomeninges. We report the case of a girl with a giant hairy nevus and numerous small nevi since birth. Within the first 2 years of life she developed clinical features of increased intracranial pressure and West s syndrome. At 2 years of age she presented a right facial palsy and myelopathy. Brain and spinal magnetic resonance imaging demonstrated meningeal infiltration. Diagnosis of NCM was established by a detailed cytologic analyses of the cerebrospinal fluid that revealed melanocytic cells. She received palliative treatment. The girl died 2 months after. Patients with large or multiple congenital melanocytic nevi should be carefully followed up with clinical examination and neuroimaging to detect NCM. At present there is no curative treatment. The association of NCM and West s syndrome has not been previously described.

Fatal Outcome↗

Hamartoma of the suprasellar cistern in a 5-year-old girl.

A 5-year-old girl with precocious puberty secondary to a suprasellar hamartoma is presented. Magnetic resonance imaging (MRI) revealed a lesion without attachment to the tuber cinereum or the mamillary bodies. Total resection of the tumour was performed.

Child, Preschool↗

Genetic interactions between Hsp90 and the Cdc2 mitotic machinery in the fission yeast Schizosaccharomyces pombe.

In Schizosaccharomyces pombe, wee1 encodes a tyrosine kinase that inhibits entry into mitosis by phophorylating Cdc2, the universal cyclin-dependent kinase (Cdk) that regulates the G2/M transition in all eukaryotic cells. A search for suppressors of the G2 arrest caused by overexpression of weel led to the isolation of a new allele of swo1 (named swo1-w1), the gene coding for chaperone Hsp90, which is required to stabilise Weel. The swo1-w1 allele carries a glycine to aspartic acid substitution at amino acid 155 that results in a partial loss of Hsp90 function. Cells bearing the swo1-w1 mutation in combination with the point mutation cdc2-33 or cdc2-M26 showed severe mitotic defects. Genetic interactions were not observed in combination with point mutations in other cdc genes, suggesting that Cdc2 specifically interacts with Hsp90. This synthetic lethal swo1-w1 cdc2-33 (or cdc2-M26) strain had normal levels of Cdc2 protein and histone H1 phosphorylation activity, indicating that Hsp90 is required to enable Cdc2 to interact with its mitotic substrates or regulators, rather than for its proper folding or stabilisation. In a wild-type background, swo1-w1 mutant cells were sensitive to temperature as well as to other stress agents, such as KCI, ethanol and formamide. Under these stressful growth conditions, the swo1-w1 cells displayed anaphase B arrest and aberrant septation patterns, indicating that a subset of proteins involved in mitosis and cytokinesis is highly dependent on chaperone Hsp90 for function.

Alleles↗