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Biomedical subjects

R Muñoz

Publications and source records attributed to R Muñoz.

At least 55 records · Page 3Linked to original sources
PubMed1999

Analysis of indirect signs of microprolactinoma at MR imaging.

OBJECTIVE: To evaluate the diagnostic reliability/value of microprolactinoma indirect signs at MRI. METHODS AND MATERIAL: A prospective study was carried out over 3 years on 26 women with microprolactinoma (MiP group) and 106 healthy female volunteers as a control group. Size, glandular morphology, pituitary stalk inclination and sellar bony floor erosion were measured and a comparative statistical analysis between both groups was performed. RESULTS: Patients from the MiP group showed a significantly bigger glandular size than women in the control group, although the glandular morphology did not present significant differences between both groups. Only 5% of normal glands measured over 7.5 mm in height and none of them reached 9 mm, while up to 42.3% of the MiP group scored over 7.5 mm and 19.2% over 9 mm. Mean stalk inclination for the MiP group was 4.6 +/- 3.1 degrees and 3.5 +/- 2.7 degrees for the control group with no significant differences. Five microprolactinomas were located on the glandular midline, 11 on the left side and ten on the right side. No relationship between the microadenoma location inside the gland and stalk inclination was found. From 21 microprolactinomas with eccentric location, 17 coincided with the sellar floor excavation; eccentric excavation presented significant differences between both groups, but not the central excavation. CONCLUSION: From all indirect sings of microprolactinoma analyzed in this study, only a gland height over 9 mm, and an eccentric sellar excavation of at least 3 mm are reliable signs to support its diagnosis.

Adolescent↗
PubMed1999

Limited sampling model for area-under-the-curve monitoring in pediatric patients receiving either Sandimmune or Neoral cyclosporin A oral formulations.

Several limited sampling equations were tested to predict the area under the curve (AUC) of cyclosporin A (CsA) at steady state in 10 children with end-stage renal disease receiving oral CsA 2.5 mg/kg b.i.d. as two different formulations, namely Sandimmune and Neoral, according to a randomized crossover design with a one-month washout period. AUC was significantly correlated with CsA concentration at 5 h. The equation derived from this single concentration time point was able to adequately predict the AUC for Sandimmune but not for Neoral. The equation derived from CsA concentration data, measured at 2 and 12 h, significantly improved predictive performance in terms of bias and precision, allowing adequate AUC predictions in both formulations. CsA concentration at 2 h was also able to predict Cmax, while the concentration at 12 h corresponded to the trough value in a b.i.d. dosing scheme. Therefore, it is concluded that a limited sampling model including concentration data at 2 and 12 h allows the estimation of AUC, Cmax and trough levels, yielding a complete profile in patients exposed to CsA as Sandimmune or Neoral. Hence, this model can be used for therapeutic monitoring of CsA levels in pediatric patients being switched from one formulation to another.

Administration, Oral↗
PubMed1999

Cement for stabilisation of industrial residues containing heavy metals.

A method aimed at decreasing the toxicity of heavy metals [namely, Zn(II) and Cr(III)] in real polluted residues by immobilisation has been developed. The residues were processed either with two cement-type stabilisers or lime. The cement-type stabilisers were Portland cement and Depocrete SM/2 at the self-generated pH (ca. 11) which afforded physical as well as chemical potential for the immobilisation of heavy metals. The other stabiliser, lime, reduced organic compounds, thus favouring the decrease of the chemical oxygen demand (COD) and endowing the residue with better mechanical properties for transport. After leaching the stabilised residues using the standard leaching test [Order 13/10/89, Boletín Oficial del Estado (BOE) 270 10/11/89], three ways for establishing the toxicity of the treated residues were used, namely: (1) the ecotoxicity test using Photobacterium phosphoreum (DIN 38 412); (2) determination of the concentration of heavy metals by atomic absorption spectrometry (AAS); (3) determination of the COD or oxygen required for complete chemical oxidation of a water sample. Portland cement (20%) blended with Depocrete SM/2 (3%) acted as an effective stabiliser for residues containing heavy metals as it increased the ecotoxicity index (EC50) by more than five times. Thus the heavy metal concentration in the leaching liquid was lowered to less than 0.1 mg l-1. The addition of 5% of lime afforded a residue easily transportable from the place of treatment to the landfill. The precision of the method was studied in terms of both repeatability and reproducibility. The values found with respect to EC50 and expressed as the relative standard deviation (RSD) were 1.6% and 5.1%, respectively.

Environmental Pollution↗
PubMed1999

First molecular characterization of a uridine diphosphate galacturonate 4-epimerase: an enzyme required for capsular biosynthesis in Streptococcus pneumoniae type 1.

Uridine diphosphate galacturonate 4-epimerases (UDPGLEs) are enzymes that convert UDP-glucuronate into UDP-galacturonate. Although the presence of UDPGLEs has been reported in prokaryoic and eukaryotic organisms, the genes coding for these enzymes are completely unknown. The galacturonic acid-containing capsular polysaccharide of Streptococcus pneumoniae type 1 is synthesized through the action of a specific UDPGLE. We have constructed a defined deletion mutant in the cap1J gene (one of the 15 cap1 genes responsible for the synthesis of the type 1 capsule) that exhibited an unencapsulated phenotype. This mutant was unable to synthesize UDPGLE, suggesting that Cap1J was the type 1-specific UDPGLE of S. pneumoniae. Escherichia coli cells harbouring the recombinant plasmid pRMM38 (cap1J) overproduced a 40 kDa protein, characterized as Cap1J on the basis of the N-terminal amino acid sequence analysis, and expressed high levels of enzymatically active Cap1J epimerase. Cap1J was partially purified, although purification to electrophoretic homogeneity inactivated the enzyme irreversibly. The enzyme has the following characteristics: K(m) for UDP-glucuronate, 0.24 mM; pH optimum, 7.5; equilibrium constant (in the direction of UDP-galacturonate formation), 1.3; and an approximate M(r) of 80,000 for the active form. The Cap1J protein exhibited a fluorescence emission spectrum similar to that of NADH. Upon inactivation with p-hydroxymercuribenzoate, the addition of NAD+ and 2-mercaptoethanol were sufficient to reactivate the enzyme. Among several compounds tested, UDP-galactose and UDP-xylose exhibited the highest inhibition of the UDPGLE activity. Inactivation of UDPGLE activity was also observed in the presence of UMP and several reducing sugars. To our knowledge, this is the first example of a thoroughly molecular characterization of a UDPGLE.

Amino Acid Sequence↗
PubMed1999

Characterization of the type 8 capsular gene cluster of Streptococcus pneumoniae.

The complete nucleotide sequence of the capsular gene cluster (cap8) responsible for the biosynthesis of the capsular polysaccharide of Streptococcus pneumoniae type 8 has been determined. The cap8 gene cluster, located between the genes dexB and aliA, is composed of 12 open reading frames. A 14.7-kb DNA fragment embracing the cap8 genes was sufficient to transform an unencapsulated type 3 S. pneumoniae strain to a strain with the type 8 capsule. A possible scenario for the evolution of pneumococcal types 2 and 8 is outlined.

Base Sequence↗
PubMed1999

Construction of a new Streptococcus pneumoniae-Escherichia coli shuttle vector based on the replicon of an indigenous pneumococcal cryptic plasmid.

The nucleotide sequence of a cryptic plasmid (pRMG1) isolated from a type 1 Streptococcus pneumoniae has been determined and two recombinant plasmids, pRMGE1 and pRMGE2, bearing the pRMG1 replicon have been constructed. pRMGE2 is a shuttle vector for Escherichia coli and S. pneumoniae. The important characteristics of this cloning vector are: a size of 5.5 kb including a 1.4 kb fragment of pRMG1 (containing a double-stranded replication origin and an open reading frame encoding a putative replication initiation protein), a multicloning site, two antibiotic resistance markers for selection of plasmid containing cells, and blue-white colony screening in E. coli for identification of insert-containing plasmids.

Base Sequence↗
PubMed1998

Molecular structure of the gene cluster responsible for the synthesis of the polysaccharide capsule of Streptococcus pneumoniae type 33F.

The organization and nucleotide sequence of the capsular gene cluster involved in the biosynthesis of the type 33F capsular polysaccharide of Streptococcus pneumoniae have been determined. The complete type 33F operon (cap33f) is composed of 14 potential open reading frames where the last ten genes are group-specific. Putative functions have been assigned to several gene products by sequence comparison with the proteins included in the databases. A functional promoter located immediately upstream from the first gene of the cap33f gene cluster has been demonstrated. A 20 kb DNA fragment containing the cap33f genes and the operon promoter was sufficient to transform a S. pneumoniae type 3 unencapsulated mutant to the type 33F capsule.

Bacterial Capsules↗
PubMed1998

Serum beta-2 microglobulin is a marker of high bone remodelling in elderly women.

Beta-2 microglobulin (beta2m), the water soluble extrinsic light chain of class I MHC, has been recently isolated from the adult bone culture medium. Serum beta2m plays a role as a bone-derived growth factor regulating both osteoblast and osteoclast cell activity. Serum beta2m has been proposed as a bone remodeling biological marker in high bone turnover conditions. The purpose of our study was to determine the relationship between beta2m and vitamin D status in post-menopausal women. We have studied 44 healthy women from 20 to 80 years with normal hepatic and renal function, without diabetes mellitus and/or inflammatory, tumoral or infectious diseases. We measured the serum levels of calcium, phosphorus, parathyroid hormone (PTH), vitamin D binding protein (DBP), 25-OHD3 (calcidiol), 1,25(OH)2D3 (calcitriol) and beta2m. Serum beta2m levels increased with age (r = 0.54, P < 0.001). Post-menopausal women had higher serum levels than pre-menopausal women of beta2m (1.76 +/- 0.22 mg/l vs. 1.35 +/- 0.2 mg/l, P < 0.01); PTH (61.5 +/- 7.5 ng/ml vs. 39 +/- 6 ng/ml, P < 0.001) and lower serum levels of 25-OHD3 (7.5 +/- 2.3 ng/ml vs. 18.2 +/- 2.5 ng/ml, P < 0.001). Moreover, serum levels of beta2m were negatively correlated with 25-OHD3 (r = -0.34, P < 0.05) and with ionized calcium (r = -0.45, P < 0.01) and positively with PTH (r = 0.48, P < 0.01). These results support the role of beta2m as a regulator of bone metabolism and its potential use as a marker of high bone turnover in post-menopausal women, specially in elderly women with vitamin D deficiency and secondary hyperparathyroidism.

Adult↗
PubMed1998

Inability of the acidic fibroblast growth factor mutant K132E to stimulate DNA synthesis after translocation into cells.

Acidic fibroblast growth factor (aFGF) is a potent mitogen. It acts through activation of specific cell surface receptors leading to intracellular tyrosine phosphorylation cascades, but several reports also indicate that aFGF enters cells and that it has an intracellular function as well. The aFGF(K132E) mutant binds to and activates fibroblast growth factor receptors equally strongly as the wild-type, but it is a poor mitogen. We demonstrate that aFGF(K132E) enters NIH 3T3 cells and is transported to the nuclear fraction like wild-type aFGF. A fusion protein of aFGF(K132E) and diphtheria toxin A-fragment (aFGF(K132E)-DT-A) and a similar fusion protein containing wild-type aFGF (aFGF-DT-A) were reconstituted with diphtheria toxin B-fragment. Both fusion proteins were translocated to the cytosol by the diphtheria toxin pathway and subsequently recovered from the nuclear fraction. Whereas translocation of aFGF-DT-A stimulated DNA synthesis in U2OSDR1 cells lacking functional fibroblast growth factor receptors, aFGF(K132E)-DT-A did not. The mutation disrupts a protein kinase C phosphorylation site in the growth factor making it unable to be phosphorylated. The data indicate that a defect in the intracellular action of aFGF(K132E) is the reason for its strongly reduced mitogenicity, possibly due to inability to be phosphorylated.

3T3 Cells↗
PubMed1998

Evidence for horizontal transfer from Streptococcus to Escherichia coli of the kfiD gene encoding the K5-specific UDP-glucose dehydrogenase.

Capsular polysaccharides are important virulence factors both in Gram-positive and Gram-negative bacteria. A similar cluster organization of the genes involved in the synthesis of bacterial exopolysaccharides has been postulated in both cases, suggesting that these clusters evolved by module assembly. Horizontal gene transfer has been postulated to explain the polymorphism found in these cellular polymers. The cap1 K and cap3A genes coding for the pneumococcal type 1 and type 3 UDP-glucose dehydrogenases, respectively, have been compared with other UDP-sugar dehydrogenases. We have observed that the evolutionary distance between Cap1K and Cap3A is approximately equal to that found between Cap1K (or Cap3A) and other UDP-GlcDH of families evolutionarily distant like KfiD, the dehydrogenase from Escherichia coli K5. On the basis of comparisons of G + C content, patterns of synonymous and nonsynonymous substitutions, dinucleotide frequencies, and codon usage bias, we conclude that the kfiD gene has been introduced into E. coli from an exogenous source, probably from a streptococcal species.

Bacterial Capsules↗
PubMed1998

Rat models of normocalcemic hypercalciuria of different pathogenic mechanisms.

Hypercalciuria was induced in female Sprague-Dawley rats, aged 40+/-2 days, by 7-day administration (mean+/-SEM) of calcitriol (5.4+/-0.1 ng/100 g per day, intraperitoneal), furosemide (14.9+/-1.9 mg/100 g per day, oral), or ammonium chloride (3.8+/-0.1 mEq/100 g per day, oral). Calciuria increased from 1.9+/-0.2, 1.6+/-0.2, and 1.9+/-0.3 to 5.4+/-0.5, 4.0+/-0.9, and 5.4+/-0.5 mg/100 g per day in the calcitriol (VD, n = 9), furosemide (F, n = 6), and ammonium chloride (AC, n = 10) groups, respectively. Calciuria did not change (1.9+/-0.3 vs. 1.6+/-0.1 mg/100 g per day) in control rats (n = 8). Ninety-six percent of treated rats became hypercalciuric as assessed by urine calcium excretion above the 90th percentile of normal values. Hypercalciuria was of similar degree in the three groups of rats and was not associated with hypercalcemia, metabolic acidosis, severe serum electrolyte imbalance, or growth impairment. VD rats had low serum parathyroid hormone (PTH) concentrations (3.0+/-0.5 pg/ml vs. 15.8+/-1.3 pg/ml in controls, P <0.05), whereas serum PTH was not significantly elevated in F rats (16.2+/-1.8 pg/ml). Thus, the protocol caused three forms of hypercalciuria that mimicked the clinical conditions of idiopathic hypercalciuria in humans and may clearly be differentiated according to their mechanism of production. This experimental model of normocalcemic hypercalciuria may be useful to clarify unknown aspects of pathogenesis and pathophysiology of idiopathic hypercalciuria in children.

Animals↗
PubMed1998

[Electromagnetic interference between automatic defibrillators and digital and analog cellular telephones].

BACKGROUND AND OBJECTIVES: Functional pacemaker interference by mobile telephones has been described with analogical systems and with possible greater influence, digital systems, including inhibition and inadequate pacing. The influence of both system has not been extensively studied in patients with implantable cardioverter defibrillators (ICD). PATIENTS AND METHODS: We studied the influence of mobile phones, both digital and analogic network, on the performance of several models of defibrillators, in a standardised test set up designed to provide high sensitivity. The purpose of our study was to establish whether there are any influences on ICD functions, both in in vivo and in in vitro models. Several mobile phones, with different transmission powers, were moved towards the defibrillator and the electrode, under continuous documentation of defibrillator sensing and interrogation afterwards. The experimental model was performed with the aid of an arrhythmia simulator (Intersim) and demo-defibrillators. The tests were repeated both in and out of a solution of saline water with an impedance within normal human limits. RESULTS: Partial loss of telemetry was found in 14 patients, 8 with analogical phones and 6 with digital phones. Fourteen patients showed alterations only on the surface electrocardiogram channel and five on the intracavitary channel. The same results were reproduced in the in vitro model. However, the in vitro test allowed us to simulate multiple ventricular arrhythmias, and demonstrate the normal sensing and functioning of the defibrillator during a "spontaneous" arrhythmia. After testing, we demonstrate that no real oversensing/undersensing was documented in any device. There was no evidence of ICD reprogramming or pacing inhibition. In particular, no inadequate therapies were delivered. CONCLUSIONS: a) in our series, we have not demonstrated clinically significant electromagnetic interferences with mobile phones of digital or analogical networks: b) the in vitro model allowed us to conclude that even if a spontaneous arrhythmia appears, the function of the defibrillator is not altered; c) the use of mobile phones seems to be safe for defibrillator patients, and d) however, some basic rules, such as to maintain the phone at least 15 cm away from the defibrillator, are advised.

Defibrillators, Implantable↗
PubMed1998

Characterization of IS1515, a functional insertion sequence in Streptococcus pneumoniae.

We describe the characterization of a new insertion sequence, IS1515, identified in the genome of Streptococcus pneumoniae I41R, an unencapsulated mutant isolated many years ago (R. Austrian, H. P. Bernheimer, E. E. B. Smith, and G. T. Mills, J. Exp. Med. 110:585-602, 1959). A copy of this element located in the cap1EI41R gene was sequenced. The 871-bp-long IS1515 element possesses 12-bp perfect inverted repeats and generates a 3-bp target duplication upon insertion. The IS encodes a protein of 271 amino acid residues similar to the putative transposases of other insertion sequences, namely IS1381 from S. pneumoniae, ISL2 from Lactobacillus helveticus, IS702 from the cyanobacterium Calothrix sp. strain PCC 7601, and IS112 from Streptomyces albus G. IS1515 appears to be present in the genome of most type 1 pneumococci in a maximum of 13 copies, although it has also been found in the chromosome of pneumococcal isolates belonging to other serotypes. We have found that the unencapsulated phenotype of strain 141R is the result of both the presence of an IS1515 copy and a frameshift mutation in the cap1EI41R gene. Precise excision of the IS was observed in the type 1 encapsulated transformants isolated in experiments designed to repair the frameshift. These results reveal that IS1515 behaves quite differently from other previously described pneumococcal insertion sequences. Several copies of IS1515 were also able to excise and move to another locations in the chromosome of S. pneumoniae. To our knowledge, this is the first report of a functional IS in pneumococcus.

Amino Acid Sequence↗
PubMed1998

Bioavailability of two oral formulations of cyclosporin A in uremic children before renal transplantation.

The bioavailability of two oral formulations of cyclosporin A (Sandimmun and Neoral) was assessed in 10 children with end-stage renal disease (ESRD), while at a steady state on a dialytic procedure. The study was performed according to a randomized, double blind, cross-over design, allowing a 1-month washout period between studies. Each patient received 2.5 mg/microg of oral cyclosporin A every 12 h, either Sandimmun (SAN) or Neoral (NEO). Serum concentrations of cyclosporin A were determined serially during a 24 h period, after the 5th dose of cylosporin. Serum concentrations against time curves were constructed and bioavailability of both medications, expressed as AUC and Cmax, were compared. A statistically significant increase was observed in the AUC and Cmax of NEO, which were 90% and 130% higher, respectively, than those of SAN. Considering that the internationally accepted criteria for bioequivalence allows a 20% variation in AUC and Cmax, it appears that Neoral and Sandimmun do not bear bioequivalence in children with ESRD. Notwithstanding, there were no significant differences in trough levels between both formulations. We conclude that, if trough levels are the only source of information for dosing design, Neoral could be substituted for Sandimmun on a 1:1 basis. However, a 1:1 drug substitution is not suitable when AUC is used in children with ESRD.

Administration, Oral↗
PubMed1998

Renal graft survival in children with early acute rejection.

Acute rejection episodes (AREs) are an important cause of morbidity and mortality in children following renal transplantation. For the purpose of this study, the diagnosis of early rejection was established when it developed within the first 6 months post-transplantation. The impact of an early ARE on patient and graft survival areas was studied in 44 patients who received their grafts between January 1987 and December 1995. Group I (GI) was comprised of 25 patients who developed 30 ARE. They were compared to 19 age- and sex-matched controls without ARE, group II (GII), who were transplanted during the same time-period and received similar long-term immunosuppressive triple therapy, oral prednisone, azathioprine and cyclosporine A. The ARE was confirmed by renal biopsy in 83% of the cases. Morbidity, mortality and graft function were assessed statistically at baseline, 12 and 24 months after transplantation. Seven GI patients lost their grafts during an ARE; in 4 cases death that was related to opportunistic infections presenting during or soon after anti-rejection therapy, whereas 3 patients who survived lost their grafts due to thromboses or infections, also as a consequence of ARE. The GI graft survival rates were 76% and 72% at 12 and 24 months post-transplant, respectively, whereas the graft survival rate of GII patients was 100% at both evaluation periods. The patient survival rate was 84% in GI and 100% in GII patients at 24 months. No statistically significant differences of renal function were found between and/or within groups at 12 and 24 months. Recipients of living related donor (LRD) and cadaveric donor (CD) kidneys were evaluated independently of the group to which they were allocated. The acute rejection ratio (number of AREs/number of transplants) was 0.61 in LRD and 0.38 in CD (differences non-significant). This study concludes that AREs are an important cause of patient and graft loss, with opportunistic infections being a major threat to be considered during aggressive anti-rejection therapy. The renal function was normal after long-term follow-up in both groups of patients, regardless of ARE.

Acute Disease↗
PubMed1998

[Study of the factors determining an unexpected occurrecne of Chagas cardiomyopathy in Sucre, Bolivia].

The purpose of this case-control study carried out between February 1, 1994 and December 22, 1994 at the "Instituto de Gastroenterologia Boliviano-Japonés" in Sucre, Bolivia was to determine risk factors for chronic Chagas cardiomyopathy in adult patients with positive serological tests for Trypanosoma cruzi. A total of 196 subjects were included. Inclusion criteria were positive serological tests for Trypanosoma cruzi, residence in the city of Sucre, Bolivia for at least 3 months, and age over 14 years. There were 62 cases presenting electrocardiographic findings consistent with Chagas cardiomyopathy and 134 controls presenting normal electrocardiographic findings. Both cases and controls underwent a standardized protocol including physical examination and laboratory tests. Interviews were set up to evaluate personal and familial history of Chagas disease, socioeconomic status, and presence of Triatoma infestans in the home. Bivariate analysis of data indicated that Chagas cardiomyopathy was associated with the following risk factors: heart rate (p < 0.05), fecaloma (p < 0.05), occupation requiring strenuous physical exertion (p < 0.001), proximity with domestic animals (p < 0.005), especially pigs (p < 0.005), dwelling features including outbuildings, more than 2 bedrooms, and inside ceilings (p < 0.001). Multivariate analysis revealed the following risk factors: occupation requiring strenuous physical exertion (p < 0.005), a yard around the house (p < 0.05), and inside ceilings (p < 0.05). The results of this study show that prevention of chronic Chagas cardiomyopathy in Sucre, Bolivia will depend on improvement of living conditions.

Adolescent↗
PubMed1997

Effect of mutation of cytoplasmic receptor domain and of genistein on transport of acidic fibroblast growth factor into cells.

Acidic fibroblast growth factor (aFGF) binds to specific transmembrane receptors and is partly transported to a nuclear location. To study this transport we made a kinase-negative mutant of FGF receptor 4 as well as one where the major part of the cytoplasmic receptor domain was deleted, and expressed them in U2OSDr1 cells that lack functional FGF receptors. All receptors mediated endocytic uptake of aFGF. Translocation of the growth factor across cellular membranes was assayed using aFGF with a C-terminal CAAX-motif, which signals addition of a farnesyl group onto the protein once in the cytosol. CAAX-tagged aFGF was farnesylated when incubated with cells containing wild-type or kinase-negative receptors. It was not farnesylated in cells expressing the deleted receptor, or when the incubation was in the presence of genistein. aFGF incubated with cells transfected with wild-type or kinase-negative receptors, but not with the deleted receptor, was partly recovered from the nuclear fraction in the absence, but not in the presence of genistein. The data indicate that the cytoplasmic receptor domain, but not the active kinase, is required for transport of the growth factor into cells, and that genistein inhibits the process.

3T3 Cells↗