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Biomedical subjects

J C Ruiz

Publications and source records attributed to J C Ruiz.

At least 55 records · Page 3Linked to original sources
PubMed2001

Characterisation of three chromosomal ends of Leishmania major reveals transcriptional activity across arrays of reiterated and unique sequences.

The 36 chromosomes of the parasite Leishmania major range in size from 200 kb to approximately 2.5 Mb and variation between homologues seems to be restricted to the telomeric and subtelomeric regions. We have isolated three cosmids carrying the telomere hexameric repeat and assigned them to the extreme location of chromosomes 3, 7 and 20. When considering the distribution of repetitive sequences, Southern analysis of the three chromosomal ends indicated the existence of at least two classes of chromosomal extremities: one of them is composed almost exclusively of unique sequences and the other is characterised by patches of both reiterated and unique sequences. We devised a transfection-based strategy that allowed the determination of a map of transcripts in each of the regions examined. Sequencing of the chromosome 20 cosmid revealed the existence of a novel class of reiterated sequence, LST-R378, and 10 ORFs drawing a map of putative genes compatible with the map of transcripts.

Animals↗
PubMed2001

The Leishmania genome project: new insights into gene organization and function.

The sequencing of Leishmania major Friedlin chromosome 1 (Chr1), Chr3, and Chr4 has been completed. and several other chromosomes are well underway. The complete genome sequence should be available by 2003. Over 1,000 full-length new genes have been identified, with the majority (approximately 75%) having unknown function. Many of these may be Leishmania (or kinetoplastid) specific. Most interestingly, the genes are organized into large (> 100-500 kb) polycistronic clusters of adjacent genes on the same DNA strand. Chr1 contains two such clusters organized in a "divergent" manner, i.e., the mRNAs for the two sets of genes are both transcribed towards the telomeres. Nuclear run-on analysis suggests that transcription is initiated in both directions within the "divergent" region. Chr3 and Chr4 contain two "convergent" clusters, with a single "divergent" gene at one telomere of Chr3. Sequence analysis of several genes from the LD1 region of Chr35 indicates a high degree of sequence conservation between L. major and L. donovani/L. infantum within protein-coding open reading frames (ORFs), with a lower degree of conservation within the non-coding regions. Immunization of mice with recombinant antigen from two of these genes, BTI (formerly ORFG) and ORFF, results in significant reduction in parasite burden following Leishmania challenge. Recombinant ORFF antigen shows promise as a serodiagnostic. We have also developed a tetracycline-regulated promoter system, which allows us to modulate gene expression in Leishmania.

Animals↗
PubMed2001

Hypertension and long-term renal allograft survival: effect of early glomerular filtration rate.

BACKGROUND: For many years, hypertension has been related to long-term survival of patients and kidney grafts, although the nature of this relationship has not been completely defined. The aim of this study was to analyse the influence of early glomerular filtration rate on post-transplant hypertension and on graft survival. METHODS: A total of 432 kidney transplanted patients on cyclosporin therapy, with a functioning graft for at least 1 year, were studied. They were divided into two groups depending on their early creatinine clearance: group A [<60 ml/min (n=270)] and group B [>60 ml/min (n=162)]. RESULTS: There were no differences in sex, aetiology of renal failure, number of retransplants, PRA, HLA mismatches and pre-transplant blood pressure. One year after transplantation, blood pressure was higher in group A (systolic BP 148/diastolic BP 86/mean BP 117) than in group B (systolic BP 140/diastolic BP 82/mean BP 111) (P<0.003). We observed a negative correlation between early creatinine clearance and 1-year blood pressure (P<0.01). Five and 10 year graft survival was 60 and 37% in group A and 87 and 69% in group B, respectively (P<0.000). A multivariate Cox analysis showed that 1-year blood pressure (P<0.0029, RR=1.76) and early creatinine clearance (P<0.000, RR=3.27) had a significant influence on graft survival. CONCLUSIONS: The 1-year post-transplant blood pressure is a non-immunological risk factor in long-term graft survival. Patients with a lower initial glomerular filtration rate are more susceptible to the development of secondary hypertension and worse graft survival.

Adult↗
PubMed2001

Dual x-ray absorptiometry, bioelectrical impedance, and near infrared interactance in obese women.

PURPOSE: Whether the evaluation of body composition in obese people using low-cost, simple bedside, two-compartment techniques reflects the data obtained by indirect methods such as dual x-ray absorptiometry (DEXA) remains controversial. The aim of this study was to compare the data obtained by three methods of assessment of body composition (DEXA; bioelectrical impedance, BIA; and near infrared interactance, NII). METHOD: Data on body composition obtained in 53 obese women by these three methods were compared, using the Bland and Altman procedure to test the relative validity. RESULTS: Although the correlation coefficients between DEXA and the two other methods were high, there were some major differences (limits of agreement) between data concerning fat and lean mass. CONCLUSIONS: The present study indicates that these methods cannot be considered as interchangeable and raises some questions on the use of BIA and NII as a single method of evaluation of body composition in clinical research and practice in obese populations.

Absorptiometry, Photon↗
PubMed2001

Is the depth correction using the geometric mean really necessary in a 99Tcm-DMSA scan in the paediatric population?

Determination of the left to right dimercaptosuccinic acid (DMSA) uptake ratio is theoretically one of the easiest quantitative procedures in nuclear medicine. The quantification can be performed on the posterior view, with or without the lateral view for correction of kidney depth. The geometric mean can also be determined using both the anterior and the posterior views. The aim of this study was to evaluate the occurrence of remarkable differences in the results from quantification of the relative renal function using the geometric mean and those obtained using the posterior counts only. Moreover, we evaluated to what extent the patient age influenced these differences. We reviewed 328 99Tcm-DMSA scans. The difference between the relative renal function obtained using the posterior view and that obtained using the geometric mean was calculated and analysed statistically. For the purpose of evaluating the value of performing the geometric mean calculation in patients of different ages, patients were divided into four age groups (group I, < or =2 years; group II, 3-9 years; group III, 10-18 years; group IV, >18 years). Using the Student's t test, no statistical differences were found in the relative renal function obtained by the two methods (posterior projection and geometric mean) in groups I (t = 0.01, P = 0.992) and II (t = 1.43, P = 0.155), which consisted of patients younger than 10 years (77% of the patients). In groups III and IV statistical differences were found (t = 2.27, P = 0.028 and t = 2.170, P = 0.038), respectively. We conclude that for children under 10 years it is unnecessary to perform depth correction using the geometric mean except in rare cases of major malformations and position anomalies.

Adolescent↗
PubMed2001

Linear growth in children suffering from juvenile idiopathic arthritis requiring steroid therapy: natural history and effects of growth hormone treatment on linear growth.

We assessed linear growth and final height retrospectively in a group of 24 patients suffering from juvenile idiopathic arthritis (JIA) during childhood who had received steroid therapy. In these patients, there was a significant loss of height of more than 2 standard deviations during the first years of the disease, which correlated positively with the duration of prednisone therapy. After remission of the disease and discontinuation of prednisone treatment, 70% of the patients achieved catch-up growth, although 30% showed a persistent loss of height. Their mean final height was strongly correlated with their mean height at the end of steroid therapy and was significantly different between the group of patients with catch-up growth and the group without catch-up growth. This pattern of growth observed in patients with JIA should help us to define strategies of growth hormone (GH) treatment in these patients in order to improve their final height. We have previously reported the beneficial effects on growth and body composition of 1 year of GH treatment in a group of 14 growth-retarded patients suffering from JIA who received glucocorticoid therapy. These patients (n = 13) were treated again with GH at the same dosage (0.46 mg/kg/week [0.07 mg/kg/day]) for another 3-year period. GH treatment markedly increased growth velocity in these patients, but had a minor effect on height SDS, suggesting that these children will remain short when adults. Starting GH therapy in these patients earlier after the onset of the disease may prevent growth deterioration and metabolic complications induced by chronic inflammation and long-term steroid therapy.

Anti-Inflammatory Agents↗
PubMed2000

Removal of xenoreactive antibodies by protein-A immunoadsorption: experience in 22 patients.

The presence of naturally occurring anti-Galalpha1-3Gal (antialphaGal) Ab in human serum is believed to be a major factor in the pathogenesis of hyperacute rejection of discordant organ xenografts such as the pig-to-human combination. Galalpha1-3Gal epitopes are expressed on pig tissues and the binding of anti-Galalpha1-3Gal leads to endothelial cell activation and complement-mediated hyperacute graft rejection. Several strategies have been suggested in donor animals or in the xenograft recipient to overcome the anti-alphaGal barrier. Protein-A immunoadsorption (PAIA) was developed for the in vivo removal of circulating Ab and it has been shown to be effective in cases where pathogenic auto or alloAb are present. The aim of our study was to analyze the effect of PAIA on total and xenoreactive serum anti-alphaGal immunoglobulin levels in a group of patients treated with this technique for different diseases. After three consecutive sessions of PAIA, total and xenoreactive IgG and IgM immunoglobulin levels were decreased by more than 50% of pre-treatment levels. So we conclude that PAIA is an effective method to significantly reduce circulating Ab, including xenogeneic IgM and IgG Ab. This mode of therapy might be considered as a tool to overcome hyperacute xenograft rejection. PAIA combined with other therapeutic approaches may well protect the xenograft.

Adolescent↗
PubMed2000

Measurement of visceral adipose tissue by DXA combined with anthropometry in obese humans.

OBJECTIVE: To get accurate measurements of visceral adipose tissue (VAT) using dual energy X-ray absorptiometry (DXA). DESIGN: DXA and anthropometric data and their combinations were compared to the VAT area calculated from a computed tomography (CT) single scan. SUBJECTS: 71 overweight subjects (44 women, 27 men), age: 16-70 y, BMI: 27-52 kg/m2. MEASUREMENTS: Total body and segmental tissue composition, and new parameters obtained from DXA, in addition to waist and hip circumferences and abdominal sagittal diameter measurements. RESULTS: The ratio measured at the umbilical level (sagittal diameter - subcutaneous fat width) x (transverse internal diameter)/(height) was closely related to VAT (r=0.94 for women and 0.88 for men). It gave the most predictive equation for VAT: y = 79.6x (s.e. 3.9) - 149 cm2 for the whole population (r2=0.86, P<0.0001, root mean square error=38.2 cm2. An independent relationship between lean mass or its index (r=0.52 and 0.72, P<0.001) and VAT was also found in women. CONCLUSION: This study demonstrates the potential usefulness of DXA to supply accurate measurements of VAT in addition to total body composition determination in obese subjects.

Absorptiometry, Photon↗
PubMed2000

Reduced bone mineral density at diagnosis and bone mineral recovery during treatment in children with Graves' disease.

OBJECTIVES: In children with Graves' disease, the prevalence of osteopenia is unknown, and the possible restoration of bone mass by antithyroid treatment has not been evaluated. The aim of this study was to prospectively evaluate the bone mineral density (BMD) and bone metabolism at diagnosis and after 1 and 2 years of medical treatment. Twenty-six children (19 girls and 7 boys) aged 11 +/- 3.4 years (range 3.4 to 15.3 years) were studied. STUDY DESIGN: BMD of the lumbar spine and proximal femur were measured by dual-energy x-ray absorptiometry. Values were compared with those of healthy children of similar age, sex, and pubertal stage. RESULTS: At diagnosis the mean BMD (standard deviation score [SDS]) was significantly reduced in both sites (P <.001) with a preferential loss of cortical bone (femoral BMD = -1.7 +/- 1.0 SDS) rather than trabecular bone (lumbar spine BMD = -0.8 +/- 1.1 SDS) (P =.003). Severe osteopenia (below -2 SDS) was found in 11 (42%) of 26 patients. Osteocalcin was significantly higher than in the control group (P <.0001), but other bone metabolism markers were normal. During treatment (n = 19) a significant gain in femoral (F = 14.7; P =.001) and lumbar spine (F = 5; P =.02) BMD (SDS) was observed, and none of the patients showed osteopenia. The annual percent change in the BMD values at the femoral (+23% +/- 11% and +6% +/- 4%, respectively, during the first and second years) and lumbar spine (+19% +/- 9% and +6% +/- 5%, respectively, during the first and second years) sites was greater during the first year than during the second year of treatment (P <.02 for femoral, P <.04 for lumbar spine). No significant age difference in BMD SD score or in BMD percent change values was observed. Osteocalcin returned rapidly to normal values, and all other bone metabolism markers remained in the normal range. CONCLUSIONS: In conclusion, severe osteopenia was observed at diagnosis in children with Graves' disease but was rapidly corrected after 1 and 2 years of treatment. Initial reduced bone mass with high bone turnover caused by hyperthyroidism was corrected after 1 year of euthyroid conditions.

Adolescent↗
PubMed2000

Circulating levels of matrix metalloproteinases MMP-3 and MMP-2 in renal transplant recipients with chronic transplant nephropathy.

BACKGROUND: Chronic transplant nephropathy remains the major cause of graft loss after the first year post transplant, with the exception of death with functioning graft. The histological hallmark of chronic kidney rejection is progressive fibrosis in which extracellular matrix turnover plays an important role. This turnover is regulated by several systems of connective tissue proteases, the matrix metalloproteinases family being one of them. Every metalloproteinase exerts a different function over extracellular matrix proteins and can contribute to the pathogenesis of several diseases, such as rheumatoid arthritis and glomerulonephritis. The role of metalloproteinases in the pathogenesis of chronic transplant nephropathy and in kidney transplantation has not yet been addressed. METHODS: We measured the serum levels of proMMP-1, proMMP-2 and proMMP-3 by ELISA in 40 patients with chronic transplant nephropathy, 30 with acute rejection, 30 with stable graft function for a time equivalent to chronic transplant nephropathy, 30 with stable graft function for a time equivalent to acute rejection, and 30 healthy age-paired blood donors. RESULTS: Serum proMMP-2 and proMMP-3 were significantly higher in patients with chronic transplant nephropathy than in patients with acute rejection, stable graft function and healthy donors. The most striking finding was the significant positive correlation observed between serum levels of proMMP-3 and serum creatinine, and between circulating levels of proMMP-2 and proteinuria. Serum concentration of proMMP-1 was increased in patients with acute rejection compared with those with stable graft function and healthy donors. CONCLUSIONS: Serum proMMP-2 and proMMP-3 reflect the changes of glomerular and interstitial extracellular matrix in chronic transplant nephropathy, suggesting that they could play a role in the pathogenesis of this condition. Acute rejection is associated with increased levels of proMMP-1, which could be a reflection of the stimulation induced by a number of inflammatory cytokines produced in such a process.

Acute Disease↗
PubMed2000

Hemodiafiltration with on-line endogenous reinfusion.

Paired filtration dialysis is a modified form of hemodiafiltration with a double-chamber hollow fiber. Convection is separated from diffusion, eliminating the potential risk of backfiltration (which can contain endotoxin or cytokine-inducing substances). The regeneration of high volumes of plasma ultrafiltrate obtained in the first filter allows a large plasma volume to be treated, and at the same time enables the return of many beneficial substances such as hormones, small peptides and many vitamins. Ultrafiltrate is regenerated with a charcoal-resin device and reinfused to the patient. Hemodiafiltration with on-line endogenous reinfusion is an easy and safe procedure. In addition, the method avoids risks associated with exogenous fluid infusion (endotoxin, pyrogens), allows exchange at no extra costs of large volumes of fluids and reduction in storage of fluid bags. Clinical advantages also include infusion of physiological fluid containing bicarbonate and calcium, good clinical tolerance and cardiovascular stability.

Adsorption↗
PubMed2000

Vitamin D receptor genotype and bone mineral density in Caucasian children with congenital hypothyroidism.

Recent studies in adults suggest that some of the genetic effects on bone mineral density (BMD) and bone turnover are related to allelic variation in the vitamin D receptor (VDR) genes. It has also been suggested in patients with hyperthyroidism that the VDR genotype might influence the risk of low BMD. We examined allelic influences of the VDR gene on BMD and metabolism in 42 children with congenital hypothyroidism (CH) aged 8.5 +/- 3.4 yr treated from the neonatal period and in whom we have previously demonstrated no detrimental effects to the skeleton of prolonged L-thyroxine therapy. The prevalence of the different VDR BsmI polymorphism in this population was as expected for Caucasian children (Bb heterozygote 52%, bb homozygote 31% and BB homozygote 17%). No relationship was found between VDR genotypes and BMD (SDS), nor between VDR genotypes and serum osteocalcin levels as markers of bone formation. However, urinary D-pyridinoline levels, as markers of bone resorption, were related to VDR genotypes (p<0.04). These data indicate that the VRD genotype does have some effect on bone metabolism in children with CH but the present results give no clear indication of a detrimental effect for any given VDR genotype, at least at the BsmI restriction site, on the bone mineralization of children with CH when adequately treated with thyroxine.

Adolescent↗
PubMed2000

Effects on bone metabolism of one year recombinant human growth hormone administration to children with juvenile chronic arthritis undergoing chronic steroid therapy.

OBJECTIVE: To study the effects on bone metabolism of treatment with recombinant human growth hormone (rhGH) in children with juvenile chronic arthritis (JCA) who are undergoing treatment with glucocorticoids (GC) and have severe bone lesions. METHODS: We assessed the effects of rhGH treatment (1.4 U/kg/week) on bone metabolism markers and bone density measured during a one year treatment course in 14 patients with systemic forms of JCA undergoing longterm GC treatment. RESULT: All patients at inclusion showed severe bone demineralization (mean bone density: -3.7 standard deviation score for chronological age). Compared to pretreatment values, bone formation markers (blood levels of osteocalcin and C-terminal propeptide of type 1 procollagen) and bone resorption markers (urinary hydroxyproline, pyridinoline, and deoxypyridinoline levels) increased significantly during treatment and returned to pretreatment values after discontinuation of rhGH. We observed that plasma level of osteocalcin was the best predictive variable of growth response to rhGH treatment in these patients. CONCLUSION: The results reflect an increase in bone turnover in these patients. Despite these biochemical changes no improvement of bone density was observed during the one year treatment. Treatment of longer duration is necessary to evaluate the curative effects of GH.

Adolescent↗
PubMed1999

Differences in anti-CREG antibody formation between transplanted and nontransplanted renal patients.

BACKGROUND: The aim of this study was investigation of the HLA-I cross-reactive group (CREG)-specific antibodies (Abs) in sera from patients with a failed renal transplant and from nontransplanted patients. METHODS: A total of 5292 sera from 570 patients awaiting kidney transplantation were screened for the presence of HLA-I CREG-specific Abs. Patients who had never received a transplant (group A), and those with a previous transplant and Abs either not related (group B) or related to donor specificities (group C) were studied. A further division was made for Abs directed against specificities either included in (intra-CREG) or not included in patients' HLA-CREG (extra-CREG). RESULTS: Twelve of 24 (50%) Abs produced in response to mismatched donor HLA specificities after a failed graft were intra-CREG Abs, compared to 7 of 39 (18%) Abs that were not transplant-related. CONCLUSIONS: Renal grafts showed a stronger immunogenicity than other sources of allosensitization. Our data also suggest that CREG matching may not be useful for renal allocation.

Antibodies↗
PubMed1999

The murine Bin1 gene functions early in myogenesis and defines a new region of synteny between mouse chromosome 18 and human chromosome 2.

We cloned and functionally characterized the murine Bin1 gene as a first step to investigate its physiological roles in differentiation, apoptosis, and tumorigenesis. The exon-intron organization of the >/=55-kb gene is similar to that of the human gene. Consistent with a role for Bin1 in apoptosis, the promoter included a functional consensus motif for activation by NF-kappaB, an important regulator of cell death. A muscle regulatory module defined in the human promoter that includes a consensus recognition site for myoD family proteins was not conserved in the mouse promoter. However, Bin1 is upregulated in embryonic development by E10.5 in myotomes, the progenitors of skeletal muscle, supporting a role in myogenesis and suggesting that the mouse and human genes may be controlled somewhat differently during development. In C2C12 myoblasts antisense Bin1 prevents induction of the cell cycle kinase inhibitor p21WAF1, suggesting that it acts at an early time during the muscle differentiation program. Interspecific mouse backcross mapping located the Bin1 locus between Mep1b and Apc on chromosome 18. Since the human gene was mapped previously to chromosome 2q14, the location of Bin1 defines a previously unrecognized region of synteny between human chromosome 2 and mouse chromosome 18.

Adaptor Proteins, Signal Transducing↗