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Biomedical subjects

A de la Fuente

Publications and source records attributed to A de la Fuente.

At least 19 recordsLinked to original sources

Unravelling gene networks from noisy under-determined experimental perturbation data.

Systems biology aims to study the properties of biological systems in terms of the properties of their molecular constituents. This occurs frequently by a process of mathematical modelling. The first step in this modelling process is to unravel the interaction structure of biological systems from experimental data. Previously, an algorithm for gene network inference from gene expression perturbation data was proposed. Here, the algorithm is extended by using regression with subset selection. The performance of the algorithm is extensively evaluated on a set of data produced with gene network models at different levels of simulated experimental noise. Regression with subset selection outperforms the previously stated matrix inverse approach in the presence of experimental noise. Furthermore, this regression approach enables us to deal with under-determination, that is, when not all genes are perturbed. The results on incomplete data sets show that the new method performs well at higher number of perturbations, even when noise levels are high. At lower number of perturbations, although still being able to recover the majority of the connections, less confidence can be placed in the recovered edges.

Cell Physiological Phenomena↗

Liver transplant results for hepatocellular carcinoma applying strict preoperative selection criteria.

INTRODUCTION: Liver transplantation is currently the best therapeutic option for small hepatocellular carcinoma (HC) in selected cirrhotic patients. The main aim of this study was to analyze the results of a recent series of liver transplant cirrhotic patients with small HC applying strict preoperative selection criteria. PATIENTS AND METHODS: During a period of 6 years we performed 53 liver transplants with a final diagnosis of HC on cirrhosis. The selection criteria for liver transplantation (LT) by modern imaging techniques were the Milan criteria (TNM I and II of the modified classification). RESULTS: Of the 53 patients, 44 (83%) were transplanted with preoperatively known HC, and 9 (17%) with incidental HC. The mean time on the waiting list was 74 +/- 62 days. Despite using strict selection criteria, 23 patients (43%) exceeded the Milan criteria in the specimen and 17 (32%) even exceeded the extended criteria of the UCSF. With a mean follow-up of 2 years, only two patients have developed recurrences. The overall survival at 1, 3, and 5 years was 80%, 70%, and 70%, respectively. The survival of patients that exceeded the Milan or USF criteria at 1, 3, and 5 years was 72% and 76%; 67% and 69%; 67% and 69%, respectively. CONCLUSIONS: The results of liver transplantation for HC are excellent when applying strict preoperative selection criteria. The current imaging methods lead to a considerable infrastaging percentage (30% to 40%), extending the indications for liver transplant due to HC beyond the scope that clinical reports would justify.

Carcinoma, Hepatocellular↗

Modelling and simulation for metabolomics data analysis.

The advent of large data sets, such as those produced in metabolomics, presents a considerable challenge in terms of their interpretation. Several mathematical and statistical methods have been proposed to analyse these data, and new ones continue to appear. However, these methods often disagree in their analyses, and their results are hard to interpret. A major contributing factor for the difficulties in interpreting these data lies in the data analysis methods themselves, which have not been thoroughly studied under controlled conditions. We have been producing synthetic data sets by simulation of realistic biochemical network models with the purpose of comparing data analysis methods. Because we have full knowledge of the underlying 'biochemistry' of these models, we are better able to judge how well the analyses reflect true knowledge about the system. Another advantage is that the level of noise in these data is under our control and this allows for studying how the inferences are degraded by noise. Using such a framework, we have studied the extent to which correlation analysis of metabolomics data sets is capable of recovering features of the biochemical system. We were able to identify four major metabolic regulatory configurations that result in strong metabolite correlations. This example demonstrates the utility of biochemical simulation in the analysis of metabolomics data.

Algorithms↗

Two proteins with ornithine acetyltransferase activity show different functions in Streptomyces clavuligerus: Oat2 modulates clavulanic acid biosynthesis in response to arginine.

The oat2 gene, located in the clavulanic acid gene cluster in Streptomyces clavuligerus, is similar to argJ, which encodes N-acetylornithine:glutamic acid acetyltransferase activity. Purified proteins obtained by expression in Escherichia coli of the argJ and oat2 genes of S. clavuligerus posses N-acetyltransferase activity. The kinetics and substrate specificities of both proteins are very similar. Deletion of the oat2 gene did not affect the total N-acetylornithine transferase activity and slightly reduced the formation of clavulanic acid under standard culture conditions. However, the oat2 mutant produced more clavulanic acid than the parental strain in cultures supplemented with high levels (above 1 mM) of arginine. The purified S. clavuligerus ArgR protein bound the arginine box in the oat2 promoter, and the expression of oat2 was higher in mutants with a disruption in argR (arginine-deregulated), confirming that the Arg boxes of oat2 are functional in vivo. Our results suggest that the Oat2 protein or one of its reaction products has a regulatory role that modulates clavulanic acid biosynthesis in response to high arginine concentrations.

Acetyltransferases↗

Intact Medtronic and Carpentier Edwards S.A.V.: clinical and hemodynamic outcomes over 13 years.

UNLABELLED: We report on 215 consecutive patients with isolated aortic replacement of which 91 received an Intact Medtronic (IM) prosthesis and 124 a Carpentier Edwards SAV. (CE). More than 50% of patients were over 70 years old. Follow-up was complete for 95% of patients. Mean follow-up was 6.04 years (16 days-13 years); a total of 1244 patient-years (IM 6.61years, 590 patient-years, CE 5.95 years, 670 patient-years). RESULTS: the following results are expressed for IM and CE groups respectively. Early mortality: 3.3% and 8.13%. Late mortality: 23 and 27 patients. Survival at 13 years: 53.31+/-7.63% and 47.47+/-7.9%. Major thromboembolism: 0.34% and 0.30% per patient-year. SVD: 0.16% and 0.14% per patient-year. Endocarditis: 0.33% and 0.29%. Re-operation: 0.5% and 0.44%. Over 95% of patients are re-operation free at 13 years. CONCLUSION: Intact and Carpentier valves had similar durability and clinical/hemodynamic results. Both have proved excellent aortic valve substitutes in elderly patients.

Adult↗

Renal smooth muscle tumor with features of lymphangioleiomyomatosis. Problems in histological diagnosis.

A 44-year-old woman with left kidney tumor involving the perirenal and retroperitoneal lymph nodes is presented. Imaging findings including ultrasonography and computerized tomography showed renal and para-aortic masses and no features of lymphangioleiomyomatosis or angiomyolipoma were seen. The histopathological examination was considered as a renal smooth muscle tumor with features of lymphangioleiomyomatosis. Diagnosis considerations, particularly histopathological, immunohistochemical and hormonal studies are discussed and we comment the distinction of this case from the benign mesenchymal tumors.

Adult↗

Metastatic lobular breast carcinoma to an endometrial polyp diagnosed by hysteroscopic biopsy.

BACKGROUND: Secondary tumors involving the uterus are rare, and most come from the close vicinity. Among non-gynecologic origins, breast tumors are the most frequent, being predominantly of the lobular carcinoma type. CASE: A 69-year-old woman presented with metrorrhagia. The patient had been diagnosed 4 years before with infiltrating lobular breast carcinoma. Follow-up was uneventful. She underwent hysteroscopy with biopsy. An endometrial polyp was seen. Microscopically, small malignant cells diffusely infiltrated the endometrial stroma and surrounded the atrophic endometrial glands. Immunohistochemical studies confirmed the diagnosis of metastatic lobular breast carcinoma. CONCLUSION: Although rare, breast tumors can metastasize to an endometrial polyp, even in the absence of other disseminations. Abnormal vaginal bleeding in a patient with known breast carcinoma can be the first sign of metastasis.

Aged↗

Transcription of the Escherichia coli dcw cluster: evidence for distal upstream transcripts being involved in the expression of the downstream ftsZ gene.

Escherichia coli strains VIP596 and VIP597 have been constructed to compare the amount of transcription of the ftsZ gene derived from proximal promoters in the ddlB-ftsZ region with that originating in the upstream regions of the dcw cluster. Both strains have in common a beta-galactosidase reporter fusion located at the ddlB locus, but differ in that VIP597 has a transcription terminator Omega interposon located downstream from lacZ. In addition, these strains have the ddlB, ftsQ, ftsA and ftsZ genes under the control of the IPTG-inducible promoter P(tac), allowing to control artificially ftsZ expression for normal cell division to take place. When beta-galactosidase activity was measured in VIP596 and VIP597 and compared to the levels measured in strain VIP407, in which the lacZ reporter fusion is located in the ftsZ gene, they were found to account for nearly 66% of the total transcription entering into ftsZ. This result indicates that the reduction in ftsZ transcription observed when the promoters in the ddlB-ftsA region are disconnected from the upstream sequences of the dcw cluster (as observed by Flärdh et al., Mol. Microbiol. 30 (1998) 305-316) in strain VIP490) is the direct consequence of the interruption in the transcription originated upstream and not due to the effect of such sequences on the promoters proximal to ftsZ.

Bacterial Proteins↗

A maternal inherited translocation t(1;22)(q11;p11) in two infertile brothers.

We report two infertile brothers presenting with azoospermia and oligozoospermia. Cytogenetic studies using G-banding and FISH analysis on lymphocyte cultures revealed an autosomal balanced reciprocal translocation t(1;22)(q11;p11) in both males. The same translocation was found in their mother, but not in a third fertile brother and maternal uncle suggesting that this translocation might compromise the male but not the female gametogenesis in this family.

Adult↗

CarboMedics and Monostrut valves: clinical and hemodynamic outcomes in a randomized study.

BACKGROUND AND AIM OF THE STUDY: Our aim was to compare the CarboMedics (CM) and Monostrut (M) mechanical heart valve prostheses in the aortic position. These prostheses have been studied extensively in the past, both have well-defined characteristics, and have not been modified for many years. METHODS: This randomized, prospective study included 200 consecutive patients; 100 received the CM prosthesis and 100 the M prosthesis. Both groups were statistically similar in terms of age, aortic valve lesion, and preoperative clinical and surgical characteristics. Mean follow up was 5.58 years (range: 2 months to 11 years); total follow up was 1095 patient-years (pt-yr) (CM 5.33 years, 528 pt-yr; M 5.85 years, 567 pt-yr). RESULTS: Early mortality rates were 1% in the CM group and 3% in the M group. Late mortality rates were 7% and 9%, respectively. Mean (+/- SD) survival rates at 11 years were 80.51 +/- 7.36% for the CM group and 79.62 +/- 5.59% for the M group. There were no cases of mechanical valve failure in either group. The linearized rates of major thromboembolism were 1.03% and 0.20% per pt-yr for the CM and M groups, respectively; the rates of major bleeding-events were 0.71% and 0.61% per pt-yr, respectively. The rate of paravalvular leak was 0.35% and 0% per pt-yr in the CM and M groups, respectively. Postoperative NYHA class was I-II in 95.83% of CM patients, and in 94.37% of M patients. CONCLUSION: Clinical results with CarboMedics and Monostrut prostheses are highly satisfactory, but no superiority of one valve over the other can be identified.

Adult↗

Characterization and expression of the arginine biosynthesis gene cluster of Streptomyces clavuligerus.

A cluster of genes argCJBDRGH containing most of the arginine biosynthesis genes has been found in Streptomyces clavuligerus after sequencing a 8.3 kb DNA region containing overlapping sequences of two DNA fragments known to contain arginine biosynthesis genes. Subcloning, complementation of E. coli arginine auxotrophic strains and enzymatic assays confirmed the identity of each gene. S1 nuclease mapping studies and Northern hybridization analysis revealed the formation of two large transcripts corresponding to argCJBDR and argGH. The amount of each of these mRNAs is 10 to 44 times higher in a S. clavuligerus argR-disrupted mutant than in the wild type confirming the existence of an ArgR-mediated control of arginine biosynthesis gene expression. A low level constitutive monocistronic transcript of argR was observed in S. clavuligerus cells. Most of the argGH transcript initiating at an adenine 29 nt upstream of the argG initiation codon appears to stop at a termination stem and loop structure present downstream of the argG gene.

Acetyltransferases↗

[Hepatocellular carcinoma associated to porphyria cutanea tarda and hepatitis C virus infection without cirrhosis].

The molecular basis of porphyria cutanea tarda is defective activity of hepatic uroporphyrinogen decarboxylase. A common characteristic is liver dysfunction than goes from cirrhosis to hepatocellular carcinoma. A high prevalence of hepatitis C virus markers has been demonstrated. We study a patient with PCT and hepatitis C virus markers that finally develops to hepatocellular carcinoma without previous cirrhosis. Previous studies with association of PCT and hepatitis C virus markers, have found liver diseases ranging from cirrhosis to hepatocellular carcinoma. The importance of this study is the absence of cirrhosis.

Carcinoma, Hepatocellular↗

[Intraoperative evaluation of the patency of coronary grafts].

Patency of coronary by-pass grafts is a challenge for the surgeon in order to reduce graft obstructions due to technical reasons. We analyze different published methods and show our experience with 1,010 coronary grafts whose flow was measured using a electromagnetic flowmeter. We also show our experience with infra-red angiography. We consider these two methods more practical and feasible than others because it is possible to save between 3 to 4% of the coronary grafts and to make an immediate record and to determine the relative prognosis of the grafts patency.

Coronary Angiography↗

Electrophysiological study of prefrontal neurones of cats during a motor task.

The prefrontal cortex is involved in many processes, some of which are related to motor activity such eye movements and speech. Experimental data exist that suggest that prefrontal cortical activity occurs in relation to attention, short-term memory, affective discrimination, and complex forms of motor behaviour, i.e. anticipatory preparation, motor sequences, programming of speech, etc. We were interested in studying participation of this cortical region in locomotion. For this purpose, recordings were made of unitary activity in the prefrontal cortex of chronically prepared cats walking on an exercise belt that was moving at a speed of 0.1 m/s. From a total of 63 neurones in the prefrontal area from which recordings were made, 37 (59%) changed their activity during locomotion, 28 of which (76%) increased and 9 of which (24%) decreased their frequency of discharge; the remaining 26 units (41%) showed no locomotor-related change in activity. The results obtained show that 59% of prefrontal units are involved in the locomotor process and it is reasonable to assume that their activity contributes to the control of the movements.

Animals↗

Infection of a pacemaker by Brucella melitensis.

We report a case that, to the best of our knowledge, is the only published instance of infection of a pacemaker and its leads by Brucella melitensis. Furthermore, this case suggests that B. melitensis may be able to persist around pacemaker devices despite its having been eliminated from the rest of the body. The patient was a sheep shearer who had just undergone a 45-day course of antibiotic therapy for brucella and had been considered cured on the basis of negative blood cultures.

Animal Husbandry↗

The safety and effectiveness of stepwise and low-dose administration of follicle stimulating hormone in WHO group II anovulatory infertile women: evidence from a large multicenter study in Spain.

PURPOSE: Our goal was to investigate the safety, effectiveness, and feasibility for the practicing physician of stepwise and low-dose administration of FSH in WHO group II anovulatory infertile women. METHODS: Infertile female patients (n = 234) suffering from WHO group II anovulation, and who failed to became pregnant with clomiphene citrate, were included in a multicenter, prospective, clinical study of treatment with a protocol of chronic low-dose and small incremental rises with urinary purified or highly purified FSH. Follicular development was monitored with ultrasonographic scans. RESULTS: The 234 patients received a total of 534 cycles of treatment, for a mean number of 2.3 treated cycles per patient. hCG was withheld in 65 (12.2%) cyles because of no response and in 28 (5.2%) cycles because of hyperresponse. Of the remaining 441 cycles, 419 (95%) were ovulatory, and in 198 (47.3%) of these cycles a single dominant follicle developed. There were 93 pregnancies (39.7% per patient), for a cycle fecundity rate of 17.4%. Cumulative conception rate after two treated cycles was 33.5%. There were 14 (15%) pairs of twins and 10 (10.8%) spontaneous miscarriages. The prevalence of complications was low with no cases of severe OHSS. Basal LH/FSH ratio was significantly higher in the pregnant group of patients than in nonpregnant women. CONCLUSIONS: Stepwise and chronic low-dose administration of FSH is a safe and effective method for treatment of WHO group II anovulatory infertility, mainly in those patients having high LH/FSH ratios.

Adult↗