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Biomedical subjects

A Ferrández

Publications and source records attributed to A Ferrández.

At least 19 recordsLinked to original sources
PubMed2001

Psammomatous malignant melanoma arising in an intradermal naevus.

AIMS: A wide variety of differentiation patterns may be found in malignant melanoma. Schwannian features are unusual, and mostly present in the desmoplastic variant. We report the first description of psammoma bodies in malignant melanoma. METHODS AND RESULTS: A malignant melanoma arose in an intradermal naevus of the scalp in a 51-year-old woman, displaying focal neural-like features in the form of rosette-like pseudo-meissnerian alveolar nests, as well as numerous psammoma bodies grouped in a few areas. Tumour cell immunostaining for S100, HMB45, NKI-C3, and vimentin was detected. In addition, both malignant and benign melanocytic cells showed widespread MART-1 immunoreactivity. Differential diagnosis with psammomatous melanotic schwannoma, a feature of Carney's complex, is particularly emphasized, since dermal variants of this nerve sheath neoplasm have been described. In addition, its potential relationship with cutaneous malignant melanotic neurocristic tumour is discussed. CONCLUSIONS: This is, to our knowledge, the first reported case of cutaneous malignant melanoma with psammoma bodies.

Antibodies, Monoclonal↗
PubMed2001

Biodegradation of aromatic compounds by Escherichia coli.

Although Escherichia coli has long been recognized as the best-understood living organism, little was known about its abilities to use aromatic compounds as sole carbon and energy sources. This review gives an extensive overview of the current knowledge of the catabolism of aromatic compounds by E. coli. After giving a general overview of the aromatic compounds that E. coli strains encounter and mineralize in the different habitats that they colonize, we provide an up-to-date status report on the genes and proteins involved in the catabolism of such compounds, namely, several aromatic acids (phenylacetic acid, 3- and 4-hydroxyphenylacetic acid, phenylpropionic acid, 3-hydroxyphenylpropionic acid, and 3-hydroxycinnamic acid) and amines (phenylethylamine, tyramine, and dopamine). Other enzymatic activities acting on aromatic compounds in E. coli are also reviewed and evaluated. The review also reflects the present impact of genomic research and how the analysis of the whole E. coli genome reveals novel aromatic catabolic functions. Moreover, evolutionary considerations derived from sequence comparisons between the aromatic catabolic clusters of E. coli and homologous clusters from an increasing number of bacteria are also discussed. The recent progress in the understanding of the fundamentals that govern the degradation of aromatic compounds in E. coli makes this bacterium a very useful model system to decipher biochemical, genetic, evolutionary, and ecological aspects of the catabolism of such compounds. In the last part of the review, we discuss strategies and concepts to metabolically engineer E. coli to suit specific needs for biodegradation and biotransformation of aromatics and we provide several examples based on selected studies. Finally, conclusions derived from this review may serve as a lead for future research and applications.

Amines↗
PubMed2000

Transcriptional regulation of the divergent paa catabolic operons for phenylacetic acid degradation in Escherichia coli.

The expression of the divergently transcribed paaZ and paaABCDEFGHIJK catabolic operons, which are responsible for phenylacetic acid (PA) degradation in Escherichia coli, is driven by the Pz and Pa promoters, respectively. To study the transcriptional regulation of the inducible paa catabolic genes, genetic and biochemical approaches were used. Gel retardation assays showing that the PaaX regulator binds specifically to the Pa and Pz promoters were complemented with in vivo experiments that indicated a PaaX-mediated repression effect on the expression of Pa-lacZ and Pz-lacZ reporter fusions. The region within the Pa and Pz promoters that is protected by the PaaX repressor in DNase I footprinting assays contains a conserved 15-base pair imperfect palindromic sequence motif that was shown, through mutational analysis, to be indispensable for PaaX binding and repression. PA-coenzyme A (PA-CoA), but not PA, specifically inhibited binding of PaaX to the target sequences, thus confirming the first intermediate of the pathway as the true inducer and PaaX as the only bacterial regulatory protein described so far that responds to an aryl-CoA compound. Superimposed in the specific PaaX-mediated regulation is transcriptional activation by the cAMP receptor protein and the integration host factor protein. These global regulators may adjust the transcriptional output from Pa and Pz promoters to the overall growth status of the cell.

Acetyl Coenzyme A↗
PubMed2000

Clinical, physical, sperm and hormonal data in 251 adults operated on for cryptorchidism in childhood.

OBJECTIVE: To determine the clinical, physical, sperm and hormonal status during adulthood in cryptorchid patients operated on during childhood, and to assess these variables according to the age at surgery and preoperative testicular position. PATIENTS AND METHODS: A letter was sent to all 890 patients > 18 years old who underwent surgery for cryptorchidism during childhood; 274 responded and were assessed using a sexual history, physical examination, pituitary axis study and sperm analysis. Data were complete for 251 patients (mean age 21 years, range 18-30); 196 had unilateral (25 anorchic) and 55 had bilateral cryptorchidism. Clinical, surgical and anatomopathological records at surgery during childhood were also reviewed. RESULTS: The mean (SD) age at orchidopexy was 6.4 (3.3) years and the mean age at assessment 21.1 (2.7) years. Semen samples generally showed abnormalities; 10 patients (4%) with bilateral and 57 (23%) with unilateral cryptorchidism had semen values within the normal range. There was no correlation between the sperm count and age at surgery for unilateral or bilateral cases (Spearman test). There was a significant correlation (r = - 0.41) between the sperm count and level of follicle-stimulating hormone (FSH). There were no significant differences in the sperm count for patients with different testicular locations (ANOVA) or in those treated or untreated with human chorionic gonadotrophin (Student's t-test). The only significant relationship (P < 0.001) was between the sperm count and unilateral or bilateral cryptorchidism. CONCLUSIONS: The sperm quality of adults operated on for cryptorchidism during childhood is independent of the age at surgery or testicular location, but is influenced by whether the cryptorchidism was unilateral or bilateral. FSH levels were negatively correlated with sperm density.

Adolescent↗
PubMed2000

Computational models of blood flow in the circle of Willis.

A two-dimensional, steady state model of the circle of Willis has been developed. To simulate the peripheral resistance of the cerebrovascular tree, blocks of porous media were used. Their effective resistance was kept constant, disregarding the effects of arterial auto-regulation. The model was then used to simulate different common abnormalities of the circle of Willis while a range of varying boundary conditions was imposed to the right internal carotid artery (ICA). The total flux was tabulated and compared favourably with both clinical measurements and other models of the circle of Willis. Relevant fluid dynamics effects were also observed and analysed. The present model demonstrates that the use of CFD can produce physiological results if the appropriate boundary conditions are used. We can provide clinicians with a priority list of the severity of the flux reduction for the considered abnormalities for different degrees of stenosis of the right ICA. From this study it is apparent that the redistribution of blood via the circle of Willis is mainly driven by changes in the vascular resistance of the brain rather than in the local arterial geometry. The use of valid peripheral resistances allows for a more realistic model of the circle of Willis but also highlights the need for more accurate means to estimate the vascular resistance of a patient.

Animals↗
PubMed1998

Catabolism of phenylacetic acid in Escherichia coli. Characterization of a new aerobic hybrid pathway.

The paa cluster of Escherichia coli W involved in the aerobic catabolism of phenylacetic acid (PA) has been cloned and sequenced. It was shown to map at min 31.0 of the chromosome at the right end of the mao region responsible for the transformation of 2-phenylethylamine into PA. The 14 paa genes are organized in three transcription units: paaZ and paaABCDEFGHIJK, encoding catabolic genes; and paaXY, containing the paaX regulatory gene. The paaK gene codes for a phenylacetyl-CoA ligase that catalyzes the activation of PA to phenylacetyl-CoA (PA-CoA). The paaABCDE gene products, which may constitute a multicomponent oxygenase, are involved in PA-CoA hydroxylation. The PaaZ protein appears to catalyze the third enzymatic step, with the paaFGHIJ gene products, which show significant similarity to fatty acid beta-oxidation enzymes, likely involved in further mineralization to Krebs cycle intermediates. Three promoters, Pz, Pa, and Px, driven the expression of genes paaZ, paaABCDEFGHIJK, and paaX, respectively, have been identified. The Pa promoter is negatively controlled by the paaX gene product. As PA-CoA is the true inducer, PaaX becomes the first regulator of an aromatic catabolic pathway that responds to a CoA derivative. The aerobic catabolism of PA in E. coli represents a novel hybrid pathway that could be a widespread way of PA catabolism in bacteria.

Acetyl Coenzyme A↗
PubMed1998

Molecular characterization of the phenylacetic acid catabolic pathway in Pseudomonas putida U: the phenylacetyl-CoA catabolon.

Fourteen different genes included in a DNA fragment of 18 kb are involved in the aerobic degradation of phenylacetic acid by Pseudomonas putida U. This catabolic pathway appears to be organized in three contiguous operons that contain the following functional units: (i) a transport system, (ii) a phenylacetic acid activating enzyme, (iii) a ring-hydroxylation complex, (iv) a ring-opening protein, (v) a beta-oxidation-like system, and (vi) two regulatory genes. This pathway constitutes the common part (core) of a complex functional unit (catabolon) integrated by several routes that catalyze the transformation of structurally related molecules into a common intermediate (phenylacetyl-CoA).

Acetyl Coenzyme A↗
PubMed1998

What is the relationship between spermatozoa per milliliter at adulthood and the tubular fertility index at surgical age for patients with cryptorchidism?

PURPOSE: The aim of this study was to find out the relationship in the patient with cryptorchidism between the number of spermatogonia at surgical age and spermiogram data at adulthood. METHODS: Between 1971 and 1996 the authors surgically treated 1,550 children for 2,249 undescended testis. In 21 unilateral and 41 bilateral cryptorchidism patients, both testis were biopsied at surgical procedure during childhood. We currently have spermiogram data for a patient at adulthood. RESULTS: By using the best Tubular Fertility Index (TFI) figures of both testis, the Sperman correlation index between the two parameters is r = 0.22, statistically nonsignificant. The TFI test sensitivity is 0.68 and the specificity is 0.60. The likehood ratio for a positive test result is 0.84 and the likehood ratio for a negative test result is 0.37. CONCLUSION: Although the authors have only one spermiogram, and there are few cases, they suspect the TFI is not a good index to predict the potential fertility in cryptorchidism patients.

Adult↗
PubMed1998

Influence of pretreatment lesions on histologic response to interferon therapy in chronic hepatitis C.

We have assessed the predictive value of the grade of pretreatment liver lesions on histologic response to interferon therapy in patients with chronic hepatitis C. In 93 patients with chronic hepatitis C virus (HCV) infection who showed an initial response to interferon therapy, HCV RNA load and serum aminotransferase levels together with grade of liver histologic lesions were assessed at baseline and 6 months after treatment cessation. Regression of portal and periportal necroinflammation was observed only in sustained responders (normalization of aminotransferase levels and HCV RNA clearance). Neither short-term response nor the absence of virus was associated with significant histologic changes in the liver biopsies. Logistic regression analysis showed that pretreatment histologic lesion was an independent predictive factor of biologic response in the histologic regression of lesions 6 months after cessation of interferon treatment. In conclusion, a dense inflammatory necrotic activity is a positive predictor of histologic response in interferon-treated patients with HCV.

Adult↗
PubMed1998

Characterization of the hca cluster encoding the dioxygenolytic pathway for initial catabolism of 3-phenylpropionic acid in Escherichia coli K-12.

We have identified, cloned, and sequenced the hca cluster encoding the dioxygenolytic pathway for initial catabolism of 3-phenylpropionic acid (PP) in Escherichia coli K-12. This cluster maps at min 57.5 of the chromosome and is composed of five catabolic genes arranged as a putative operon (hcaA1A2CBD) and two additional genes transcribed in the opposite direction that encode a potential permease (hcaT) and a regulator (hcaR). Sequence comparisons revealed that while hcaA1A2CD genes encode the four subunits of the 3-phenylpropionate dioxygenase, the hcaB gene codes for the corresponding cis-dihydrodiol dehydrogenase. This type of catabolic module is homologous to those encoding class IIB dioxygenases and becomes the first example of such a catabolic cluster in E. coli. The inducible expression of the hca genes requires the presence of the hcaR gene product, which acts as a transcriptional activator and shows significant sequence similarity to members of the LysR family of regulators. Interestingly, the HcaA1A2CD and HcaB enzymes are able to oxidize not only PP to 3-(2,3-dihydroxyphenyl)propionate (DHPP) but also cinnamic acid (CI) to its corresponding 2, 3-dihydroxy derivative. Further catabolism of DHPP requires the mhp-encoded meta fission pathway for the mineralization of 3-hydroxyphenylpropionate (3HPP) (A. Ferrández, J. L. García, and E. Díaz, J. Bacteriol. 179:2573-2581, 1997). Expression in Salmonella typhimurium of the mhp genes alone or in combination with the hca cluster allowed the growth of the recombinant bacteria in 3-hydroxycinnamic acid (3HCI) and CI, respectively. Thus, the convergent mhp- and hca-encoded pathways are also functional in S. typhimurium, and they are responsible for the catabolism of different phenylpropanoid compounds (3HPP, 3HCI, PP, and CI) widely available in nature.

Amino Acid Sequence↗
PubMed1997

Spontaneous ascent of the testis.

OBJECTIVE: To report confirmed cases of spontaneous testicular ascent in patients with a cryptorchid testis which had been previously placed in the scrotum. PATIENTS AND METHODS: Between 1972 and 1992, 46 cryptorchid testes (36 patients), which were previously verified to be in the scrotum by staff paediatricians or paediatric surgeons, were treated surgically. The clinical, surgical and anatomicopathological records were reviewed to determine testicular position and associated conditions, and biopsies were taken from 35 testes. RESULTS: The mean time between the last "normal' exploration until the testes ascended was 4.5 years. Before ascent, the testes were confirmed to be in the scrotum by up to seven separate recorded examinations. During surgical treatment, an open processus vaginalis was found in 18 testes. The mean (SD) tubular fertility index was 40 (37)%. CONCLUSIONS: This study confirms that a previously descended testis can ascend spontaneously. The clinical and anatomicopathological characteristics of these testes were similar to those of the cryptorchid testis.

Child↗
PubMed1997

Designing recombinant Pseudomonas strains to enhance biodesulfurization.

The dsz biodesulfurization cluster from Rhodococcus erythropolis IGTS8 has been engineered under the control of heterologous broad-host-range regulatory signals to alleviate the mechanism of sulfur repression, and it was stably inserted into the chromosomes of different Pseudomonas strains. The recombinant bacteria were able to desulfurize dibenzothiophene more efficiently than the native host. Furthermore, these new biocatalysts combine relevant industrial and environmental traits, such as production of biosurfactants, with the enhanced biodesulfurization phenotype.

Biodegradation, Environmental↗
PubMed1997

Genetic characterization and expression in heterologous hosts of the 3-(3-hydroxyphenyl)propionate catabolic pathway of Escherichia coli K-12.

We report the complete nucleotide sequence of the gene cluster encoding the 3-(3-hydroxyphenyl)propionate (3-HPP) catabolic pathway of Escherichia coli K-12. Sequence analysis revealed the existence of eight genes that map at min 8 of the chromosome, between the lac and hemB regions. Six enzyme-encoding genes account for a flavin-type monooxygenase (mhpA), the extradiol dioxygenase (mhpB), and the meta-cleavage pathway (mhpCDFE). The order of these catabolic genes, with the sole exception of mhpF, parallels that of the enzymatic steps of the pathway. The mhpF gene may encode the terminal acetaldehyde dehydrogenase (acylating) not reported previously in the proposed pathway. Enzymes that catalyze the early reactions of the pathway, MhpA and MhpB, showed the lowest level of sequence similarity to analogous enzymes of other aromatic catabolic pathways. However, the genes mhpCDFE present the same organization and appear to be homologous to the Pseudomonas xyl, dmp, and nah meta-pathway genes, supporting the hypothesis of the modular evolution of catabolic pathways and becoming the first example of this type of catabolic module outside the genus Pseudomonas. Two bacterial interspersed mosaic elements were found downstream of the mhpABCDFE locus and flank a gene, orfT, which encodes a protein related to the superfamily of transmembrane facilitators that might be associated with transport. All of the genes of the 3-HPP cluster are transcribed in the same direction, with the sole exception of mhpR. Inducible expression of the mhp catabolic genes depends upon the presence, in the cis or trans position, of a functional mhpR gene, which suggests that the mhpR gene product is the activator of the 3-HPP biodegradative pathway. The primary structure of MhpR revealed significant similarities to that of members of the IclR subfamily of transcriptional regulators. A 3-HPP catabolic DNA cassette was engineered and shown to be functional not only in enteric bacteria (E. coli and Salmonella typhimurium) but also in Pseudomonas putida and Rhizobium meliloti, thus facilitating its potential application to improve the catabolic abilities of bacterial strains for degradation of aromatic compounds.

Amino Acid Sequence↗
PubMed1993

Chronic hepatitis and cirrhosis: evaluation by means of MR imaging with histologic correlation.

To characterize the relationship between findings on magnetic resonance (MR) images and histologic changes in chronic liver disease, a prospective study was performed in 100 patients with chronic hepatitis and cirrhosis and 28 healthy subjects. Biopsy specimens, obtained in all patients before MR imaging, were evaluated with the histologic activity (HA) index; MR images were obtained with short inversion time inversion-recovery (STIR) and spin-echo sequences. On STIR images, normal livers were iso-intense to fat. Significant differences (P < .001) existed between signal intensity of normal livers and that of diseased livers, which were brighter than normal livers on STIR images. The ratio of signal intensity of liver to that of fat on STIR images was associated with an HA index grouped by severity (P < .05): Patients with higher HA scores had a brighter liver. Signal intensity ratios on MR images were statistically significantly associated with periportal and lobular necrosis and portal inflammation. The signal intensity of liver on STIR images is associated with the degree of histologic severity in patients with chronic liver disease.

Adult↗
PubMed1993

[Phage count in the waters of the Canal Imperial de Aragón and the Ebro River in Saragossa].

Saragossa city supply channel and the river Ebro (up and downstream urban sewage) were studied for the presence of coliphages and B. fragilis phages and their relationship with the bacterian faecal indicators. In the supply channel the coliphages geometric mean was of 130 ufp/100 ml, and showed no correlation with faecal and total coliforms, but it showed indirect correlation with ambient temperature. In the river Ebro the coliphages geometric mean ranged from 290 to 8,000 ufp/100 ml; the relationship with total and faecal coliforms and faecal streptococci was high, but they were temperature independent. With the methodology utilized B. fragilis phages only were recovered in samples with faecal coliforms levels > 1 x 10(4) ufc/100 ml.

Bacillus↗