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Biomedical subjects

J Oliver

Publications and source records attributed to J Oliver.

At least 19 recordsLinked to original sources

Asporin repeat polymorphism in rheumatoid arthritis.

BACKGROUND: Asporin belongs to a family of proteins associated with the cartilage matrix. OBJECTIVE: To investigate the role of the functional polymorphism consisting of an aspartic acid (D) repeat polymorphism located in the ASPN gene in the susceptibility to and clinical outcome of rheumatoid arthritis. METHODS: A total of 803 Spanish Caucasian patients with rheumatoid arthritis and 904 controls of the same ethnic origin and matched for age and sex were included in the study. The asporin D repeat polymorphism was genotyped using polymerase chain reaction with a fluorescent primer. RESULTS: No significant differences were detected in the distribution of the 10 alleles found in our population on comparing patients with rheumatoid arthritis with control groups. Nevertheless, individuals bearing D14 produced rheumatoid factor more often than the rest (85.7% v 72.1%, p = 0.006, odds ratio (OR) = 2.35, 95% confidence interval 1.21 to 4.50), and the mean (SD) onset age was higher in the group of individuals bearing D13 (50.09 (13.94)) compared with the rest (47.21 (14.31)), although the difference did not reach significance (p = 0.06). CONCLUSION: The results do not support a major role for asporin D repeat polymorphism in the susceptibility to rheumatoid arthritis. Nevertheless, they support the influence of this gene on the outcome of the disease.

Adult↗

Effects of age and recovery duration on performance during multiple treadmill sprints.

The aim of this study was to investigate the effects of age and recovery duration on performance during multiple treadmill sprints. Twelve boys (11.7 +/- 0.5 y) and thirteen men (22.1 +/- 2.9 y) performed ten consecutive 10-s sprints on a non-motorised treadmill separated by 15-s (R15) and 180-s (R180) passive recovery intervals. Mean power output (MPO), mean force output (MFO), running velocity, step length, and step rate were calculated for each sprint. Capillary blood samples were drawn from the fingertip at rest and 3 min after the tenth sprint to measure the lactate accumulation (Delta [La]). With R15, all mechanical parameters decreased significantly less in the boys than in the men over the ten sprints (MPO: - 28.9 vs. - 47.0 %, MFO: - 13.1 vs. - 25.6 %, running velocity: - 18.8 vs. - 29.4 %, p < 0.001, respectively). With R180, all mechanical values remained unchanged in the boys. In the men, MPO and MFO significantly decreased over the ten sprints (- 7.8 % and - 4.6 %, p < 0.05, respectively). The running velocity, however, did not decrease because the decrease in step rate (p < 0.001) was compensated by an increase in step length. For either recovery interval, Delta [La] values were higher in the men compared to the boys (R15: 12.7 vs. 7.7 mmol . L (-1), p < 0.001, R180: 10.7 vs. 7.7 mmol . L (-1), p < 0.05). To conclude, the boys maintained more easily their running performance than the men during repeated treadmill sprints with R15. Three-minute recovery periods were sufficient in the boys to repeat short running sprints without substantial fatigue. Despite the decrease in power and force outputs with R180, the young men were able to maintain their running velocity during the test.

Adult↗

Inducible and endothelial nitric oxide synthase genes polymorphism in inflammatory bowel disease.

To assess the influence of inducible and endothelial nitric oxide synthase gene (NOS2A and NOS3) polymorphisms in susceptibility to Crohn's disease (CD) and ulcerative colitis (UC). A total of 505 inflammatory bowel disease (IBD) patients (221 with UC and 284 with CD) and 332 ethnically matched controls were studied. Patients and controls were genotyped by polymerase chain reaction -based techniques for a multiallelic (CCTTT)(n) repeat and biallelic marker (TAAA)(n) in the promoter region of the NOS2A gene and for a T/C polymorphism at position -786 in the promoter region and a polymorphism in exon 7(298Glu/Asp) of the NOS3 gene. There was not association between NOS2A and NOS3 genotypes, alleles or haplotypes frequencies with UC, CD and controls. Our data suggest that NOS2A and NOS3 polymorphisms do not play a major role in IBD predisposition.

Case-Control Studies↗

Sex-related differences in energy balance in response to caloric restriction.

Sex-related differences in energy balance were studied in young Wistar rats fed standard chow pellets either ad libitum or in restricted amounts (60% of ad libitum intake) for 100 days. Caloric intake, indirect calorimetry, organ and adipose tissue weights, energy efficiency, liver mitochondrial respiration rate, and brown adipose tissue (BAT) uncoupling protein-1 (UCP1) content were measured. Ad libitum-fed females showed greater oxygen consumption (Vo(2)) and carbon dioxide production (Vco(2)) and lower energy efficiency than males. Caloric restriction induced a chronic drop of Vo(2) and Vco(2) in females but not in males over the period studied. Restricted females showed a better conservation of metabolic active organ mass and a greater decrease in adipose depots than restricted males. Moreover, changes of BAT size and UCP1 content suggest that BAT may be the main cause responsible for sex differences in the response of energy balance to caloric restriction. In conclusion, our results indicate that females under caloric restriction conditions deactivate facultative thermogenesis to a greater degree than males. This ability may have obvious advantages for female survival and therefore the survival of the species when food is limiting.

Adaptation, Physiological↗

Kidney-pancreas transplants: is it so difficult to start a program?

BACKGROUND: For selected patients with type 1 diabetes mellitus and end-stage renal failure, simultaneous kidney-pancreas (SKP) or pancreas after kidney (PAK) transplantation is the treatment of choice. However, it is frequently difficult to start a program for fear of serious intraabdominal complications in an immunosuppressed patient. We review our initial experience with these transplantations. METHODS: Twenty-three patients (20 SKP, 3 PAK) with type 1 diabetes mellitus received transplants between June 2000 and October 2003. All received immunosuppression therapy with thymoglobulin, prednisone, tacrolimus, and mycophenolate mofetil. The operation included portal venous drainage and exocrine enteric drainage. Rejections were biopsy-proved. Cytomegalovirus prophylaxis with gancyclovir was administered. RESULTS: The mean follow-up is 13 months (range, 1-30 months) for recipients of mean age 39 +/- 7 years (17 men, 6 women). Mean cold ischemia time for kidney was 10.2 +/- 3.9 hours, and for pancreas was 10.5 +/- 3 hours. The rate of initial graft function was 100%. Graft rejection rate was 8%. The repeat laparotomy rate was 53% (12 patients), with a mean of 0.8 procedures per patient (range, 0 to 5). At the end of follow-up, patient survival was 95%, kidney survival was 85%, and pancreas survival was 83%. Patients with a functioning graft were insulin-free, with a mean fasting glucose concentration of 79 +/- 7 mg/dL, hemoglobin A1C of 4.5% (range, 4% to 4.9%) C-peptide of 5.9 ng/mL (range, 2.1 to 12 ng/mL), and a mean serum creatinine level of 1.6 mg/dL (range, 0.9 to 4.6 mg/dL). There was 1 death, due to posttransplantation lymphoproliferative disease confined to the pancreatic graft and abdominal sepsis at 3 months posttransplantation. CONCLUSIONS: Our results are similar to those of other series of SPK or PAK transplantations: low acute rejection rates, frequent requirement for repeat laparotomy, and good patient and graft survival, permitting an excellent quality of life.

Adult↗

Renal transplantation from non-heart-beating donors: a single-center 10-year experience.

BACKGROUND: Reluctance to accept non-heart-beating donors (NHBD) as a source of kidneys, is due to medical, ethical, and logistical reasons. Evidence suggest that the short-term graft survival is similar to that of kidneys obtained from heart-beating donors (HBD). However, few studies, with long-term follow-up are available. We conducted a single-center study of kidneys obtained from NHBD, in a 14-year period. METHODS: We studied 100 patients transplanted with kidneys between 1989 and 2004, using NHBD, supported by heart compression and mechanical ventilation (n = 24), intravascular in situ cooling (n = 59), or cardiorespiratory resuscitation plus manual abdominal counterpulsation without cooling (n = 17), the last technique being used from 1998. The median follow-up was 51 +/- 51 months (range, 1 to 170). The outcomes of these procedures were compared to those of 1025 transplantations of kidneys from HBD performed during the same period. RESULTS: The characteristics of the recipients did not differ significantly between the two groups. Kidneys from NHBD showed a significantly higher rate of delayed graft function (DGF; 84% vs 26%; (P < .001), furthermore, the primary nonfunction (PNF) incidence was significantly higher with NHBD vs HBD (16% vs 10%; P < .001). The incidence of acute rejection episodes (ARE) within 3 months and at 1 year did not differ between the groups of donors; however, more NHBD kidneys were lost from ARE. The short-term (3-month and 1 year) and long-term (5 and 10 years) renal function, determined by the serum creatinine levels, and patient and graft survival were not different for kidneys obtained from NHBD. CONCLUSIONS: The incidences of PNF and DGF were significantly higher with NHBD, which produced poorer renal function at the time of hospital discharge. One-, 5-, and 10-year graft survivals and renal function did not differ between NHBD and HBD grafts. In our series, PNF was the main barrier to the use of NHBD.

Adult↗

Evolution of proteinuria after conversion from calcineurin inhibitors (CNI) to sirolimus (SRL) in renal transplant patients: a multicenter study.

Conversion from calcineurin inhibitors (CNI) to sirolimus (SRL) has become an option in patients with chronic allograft nephropathy or other conditions. However, in some cases an increase of proteinuria has been reported after such therapeutic intervention. The aim of this study was to characterize the clinical course of this so far unexplained proteinuria after conversion. We performed a retrospective analysis evaluating 94 renal transplant patients from various Spanish centers. Proteinuria (629 determinations) and clinical developments were analyzed between 6 months before and 6 months after conversion. Patients were divided into three groups according to mean proteinuria before conversion (group A: <300 mg/d; group B: 300 to 2000 mg/d; and group C: >2 g/d). The mean proteinuria level was 1.69 g/24 h (n = 312 determinations) before and 2.36 g/24 h after conversion (n = 317 determinations; P = .006), which corresponds to an overall increase of 25% (1.55 to 1.69 g/24 h considering only determinations of 1 month before and 1 month after conversion; P = NS). We could not detect any clear correlation between proteinuria and serum creatinine nor between changes of proteinuria and changes of serum creatinine. A variance analysis for repeated measures showed an increase in proteinuria compared to the preconversion values (P = .003), and when the three groups of preconversion proteinuria were evaluated separately it could be observed that this change in the evolution of proteinuria was almost completely dependent of an increase in the group C (preconversion proteinuria greater than 2 g/d; P = .03), whereas in the other two groups changes were almost irrelevant. Finally, the switch to SRL in renal transplant recipients is followed by an increase in the level of proteinuria predominantly dependent of an increase in patients with high levels of preconversion proteinuria, whereas it seems to be irrelevant in patients without or with light or moderate proteinuria. These results suggest that this might not be a direct effect of SRL.

Calcineurin Inhibitors↗

Detection and treatment of post kidney transplant hyperglycemia: a Spanish multicenter cross-sectional study.

INTRODUCTION: The prevalence of diabetes mellitus (DM) is greater among patients with solid organ transplants than in the general population, although the factors associated with posttransplant DM (PTDM) are unknown. OBJECTIVES: The objective of this study was to estimate the prevalence of and assess the risk factors for PTDM. PATIENTS AND METHODS: We included outpatients with functioning isolated solid organ allografts (kidney, liver, heart, and lung). We collected demographic and posttransplant clinical data that included DM diagnostic ADA criteria, DM treatment, DM family history, presence of hepatitis C virus (HCV), immunosuppression treatment, hypertension, and dyslipidemia. RESULTS: A total of 2178 patients included, 1410 kidney recipients, 489 liver transplants, 207 heart transplants, and 72 lung recipients. Seventeen and four-tenths percent of the patients who did not have DM prior to transplantation, developed PTDM (median time: 79 days). A greater prevalence was observed among patients with a family history, HCV, and tacrolimus treatment (with or without steroids P < .05). By logistic regression analyses, OR for these factors were 1.51, 1.65, and 1.38, respectively. Of those patients who did not suffer PTDM, 55.2% showed basal blood glucose values under 100 mg/dL; only 68% presented with a hemoglobin Alc under 6. CONCLUSIONS: The prevalence of PTDM among kidney recipients was higher than that in the general population. DM family history, HCV positive, and tacrolimus were risk factors associated with this entity.

Adult↗

The Web as an educational tool for/in learning/teaching bioinformatics statistics.

Statistics provides essential tool in Bioinformatics to interpret the results of a database search or for the management of enormous amounts of information provided from genomics, proteomics and metabolomics. The goal of this project was the development of a software tool that would be as simple as possible to demonstrate the use of the Bioinformatics statistics. Computer Simulation Methods (CSMs) developed using Microsoft Excel were chosen for their broad range of applications, immediate and easy formula calculation, immediate testing and easy graphics representation, and of general use and acceptance by the scientific community. The result of these endeavours is a set of utilities which can be accessed from the following URL: http://gmein.uib.es/bioinformatica/statistics. When tested on students with previous coursework with traditional statistical teaching methods, the general opinion/overall consensus was that Web-based instruction had numerous advantages, but traditional methods with manual calculations were also needed for their theory and practice. Once having mastered the basic statistical formulas, Excel spreadsheets and graphics were shown to be very useful for trying many parameters in a rapid fashion without having to perform tedious calculations. CSMs will be of great importance for the formation of the students and professionals in the field of bioinformatics, and for upcoming applications of self-learning and continuous formation.

Computational Biology↗

The functional genetic variation in the PTPN22 gene has a negligible effect on the susceptibility to develop inflammatory bowel disease.

The aim of this study was to assess the possible association between the protein tyrosine phosphatase non-receptor 22 (PTPN22) gene 1858C-->T (rs2476601, encoding R620W) polymorphism and inflammatory bowel disease (IBD). Our study population consisted of 1113 IBD [544 ulcerative colitis (UC) and 569 Crohn's disease (CD)] patients and 812 healthy subjects. All the individuals were of Spanish white origin. Genotyping of the PTPN22 gene 1858C-->T polymorphism was performed by real time polymerase chain reaction technology, using TaqMan 5'-allelic discrimination assay. The frequency of the PTPN22 1858T allele in healthy subjects was 6.2% compared with 6.7% in the UC patients and 5.1% in Crohn's patients. No statistically significant differences were observed when the PTPN22 1858C-->T allele and genotype distribution among CD patients, UC patients and healthy controls were compared. These results indicate that the PTPN22 1858C-->T polymorphism does not appear to play a major role in IBD predisposition in our population.

Alleles↗

Chronic allograft nephropathy: causes of death and mortality risk factors-a review of the last decade in Spain.

BACKGROUND: Improved immunosuppressive regimens and management strategies in renal transplantation (RT) have increased patient and graft survival during the last years. The aim of our study was to analyze the causes, risk factors, and evolution of mortality after renal transplantation. METHODS: We studied 3365 renal transplant recipients in adults (>18 years) who survived at least 1 year after transplantation in Spain during 1990, 1994, and 1998. The mortality rates and risk factors were analyzed employing single and multivariate Cox regression. RESULTS: The follow-up was shortest (maximum 2.5 years) for recipients transplanted in 1998. When we consider an identical follow-up period (2.5 years) for all patients, we did not observe a statistical difference in patient survival and causes of death in the three analyzed periods. Mortality was higher for men and for patients over 60 years. Cardiovascular diseases (CVD) and neoplasia were the most frequent causes of death. Graft dysfunction, as determined by creatinine level or proteinuria range in the first months, were significant factors associated with a higher risk for cardiovascular and infectious deaths. CONCLUSIONS: During the last decade in Spain, patient survival after RT (2.5 years follow-up) has remained stable. Recipient age (>60 years), male gender, and graft dysfunction in the first year were associated with a higher risk of death especially due to CVD.

Adult↗

Endogenous endothelin increases gallbladder tone and leads to acute cholecystitis in the Australian possum.

Endothelins are bioactive peptides produced by gallbladder epithelial cells. We aimed to determine the role of endothelins in acute cholecystitis. Escherichia coli lipopolysaccharide vs saline (sham) was instilled into the gallbladder lumen of Australian possums. Some animals received the non-selective endothelin antagonist, tezosentan. At 4 or 24 h, plasma and gallbladder endothelins and white blood cell count (WBCC) were determined. Acute cholecystitis was assessed using a histopathology score. In other animals gallbladder tone was determined. At 4h, a dose-dependent 60-fold increase in gallbladder endothelin level occurred (P = 0.001) but other parameters remained comparable with sham animals. Epithelial cells were endothelin-immunoreactive. At 24 h, the WBCC rose (P < 0.007), and severe cholecystitis developed. Gallbladder but not plasma endothelin levels remained elevated. Tezosentan pre-treatment resulted in a histologically normal gallbladder, but the WBCC and gallbladder endothelin levels were elevated. Lipopolysaccharide or saline instillation also caused a time-dependent increase in gallbladder tone over 4 h (P < 0.001), but not in control animals. This increase was reduced by tezosentan treatment. Gallbladder endothelin production is an early event in acute cholecystitis, increases gallbladder tone and plays a crucial role in the inflammatory process.

Animals↗

Novel sequences encoding venom C-type lectins are conserved in phylogenetically and geographically distinct Echis and Bitis viper species.

Envenoming by Echis saw scaled vipers and Bitis arietans puff adders is the leading cause of death and morbidity in Africa due to snake bite. Despite their medical importance, the composition and constituent functionality of venoms from these vipers remains poorly understood. Here, we report the cloning of cDNA sequences encoding seven clusters or isoforms of the haemostasis-disruptive C-type lectin (CTL) proteins from the venom glands of Echis ocellatus, E. pyramidum leakeyi, E. carinatus sochureki and B. arietans. All these CTL sequences encoded the cysteine scaffold that defines the carbohydrate-recognition domain of mammalian CTLs. All but one of the Echis and Bitis CTL sequences showed greater sequence similarity to the beta than alpha CTL subunits in venoms of related Asian and American vipers. Four of the new CTL clusters showed marked inter-cluster sequence conservation across all four viper species which were significantly different from that of previously published viper CTLs. The other three Echis and Bitis CTL clusters showed varying degrees of sequence similarity to published viper venom CTLs. Because viper venom CTLs exhibit a high degree of sequence similarity and yet exert profoundly different effects on the mammalian haemostatic system, no attempt was made to assign functionality to the new Echis and Bitis CTLs on the basis of sequence alone. The extraordinary level of inter-specific and inter-generic sequence conservation exhibited by the Echis and Bitis CTLs leads us to speculate that antibodies to representative molecules should neutralise the biological function of this important group of venom toxins in vipers that are distributed throughout Africa, the Middle East and the Indian subcontinent.

Amino Acid Sequence↗

Molecular cloning of phospholipases A(2) from venom glands of Echis carpet vipers.

Venom toxin-specific antibodies offer a more rational treatment of snake envenoming than conventional antivenom. Here, we describe novel cDNAs encoding phospholipase A(2) (PLA(2)) isoforms from venom gland RNA of Echis pyramidum leakeyi (Epl), Echis sochureki (Es) and Echis ocellatus (Eo). The deduced amino acid sequences of these cDNAs encoded proteins with high overall sequence identity to the viper group II PLA(2) protein family, including the 14 cysteine residues capable of forming seven disulphide bonds that characterize this group of PLA(2) enzymes. Comparison of the PLA(2) sequences from Echis with those from related vipers failed to make significant geographic, taxonomic or PLA(2)-function distinctions between these Echis PLA(2) isoforms. However, their deduced hydrophilicity profiles revealed a conserved tertiary structure that we will exploit, by epidermal DNA immunization, to generate PLA(2)-neutralizing antibodies with polyspecific potential.

Amino Acid Sequence↗

Temporal precision of interceptive action: differential effects of target size and speed.

The duration of movements made to intercept moving targets decreases and movement speed increases when interception requires greater temporal precision. Changes in target size and target speed can have the same effect on required temporal precision, but the response to these changes differs: changes in target speed elicit larger changes in response speed. A possible explanation is that people attempt to strike the target in a central zone that does not vary much with variation in physical target size: the "effective size" of the target is relatively constant over changes in physical size. Three experiments are reported that test this idea. Participants performed two tasks: (1). strike a moving target with a bat moved perpendicular to the path of the target; (2). press on a force transducer when the target was in a location where it could be struck by the bat. Target speed was varied and target size held constant in experiment 1. Target speed and size were co-varied in experiment 2, keeping the required temporal precision constant. Target size was varied and target speed held constant in experiment 3 to give the same temporal precision as experiment 1. Duration of hitting movements decreased and maximum movement speed increased with increases in target speed and/or temporal precision requirements in all experiments. The effects were largest in experiment 1 and smallest in experiment 3. Analysis of a measure of effective target size (standard deviation of strike locations on the target) failed to support the hypothesis that performance differences could be explained in terms of effective size rather than actual physical size. In the pressing task, participants produced greater peak forces and shorter force pulses when the temporal precision required was greater, showing that the response to increasing temporal precision generalizes to different responses. It is concluded that target size and target speed have independent effects on performance.

Adolescent↗