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Biomedical subjects

J L Rocha

Publications and source records attributed to J L Rocha.

15 recordsLinked to original sources
PubMed1999

Molecular analyses of the vasopressin type 2 receptor and aquaporin-2 genes in Brazilian kindreds with nephrogenic diabetes insipidus.

Nephrogenic diabetes insipidus (NDI) is associated with germline mutations in two genes: vasopressin receptor type 2 (V2(R)) in X-linked NDI, and the water channel aquaporin-2, in autosomal-recessive disease. Genetic heterogeneity is further emphasized by reports of phenotypically abnormal individuals with normal structural genes. We analyzed both genes in five Brazilian families and the aquaporin-2 gene in two Swedish families with clinical and laboratory diagnosis of NDI, by a combination of denaturing gradient gel electrophoresis (DGGE) and direct DNA sequencing. A novel polymorphism in the aquaporin-2 gene (S167S), but no disease-associated mutations in any tested individual from all seven families, was detected. In two Brazilian families, frameshift mutations were detected in the V2(R) gene: one leading to a premature stop after codon 36 and the other to a longer peptide (462 aa instead of the 373 aa wild-type protein). In two other Brazilian families, probable disease-associated missense mutations were detected: an alanine to proline at codon 163 (A163P) and an asparagine to aspartic acid at codon 85 (D85N). In one Brazilian family, both genes were structurally normal and the aquaporin-2 gene was also normal in the two Swedish kindreds. This report further extends the mutational spectrum of NDI and suggests that there are other mutational or epigenetic events inactivating the two known genes or even novel genes that underlie NDI.

Adolescent↗
PubMed1999

Inverse paradoxical embolism in a patient on chronic hemodialysis with aortic bacterial endocarditis.

We present a 45-year-old patient on chronic hemodialysis who suffered aortic endocarditis by Staphylococcus haemolyticus after bacteremia associated with a venous catheter, which was used temporarily during the maturing phase of a Cimino-Brescia arteriovenous fistula in the left forearm. Three weeks after starting antibiotic therapy, the patient suffered a septic pulmonary embolism. The catheter had been removed 4 weeks before the embolism. Thrombophlebitis of lower limbs, infection or thrombosis of the vascular access, and the involvement of right-sided cardiac structures were all discarded. We assumed that the pulmonary episode was probably a consequence of the paradoxical passage of embolic material, detached from the aortic valve, from arterial to venous circulation through the arteriovenous fistula.

Aortic Valve↗
PubMed1999

Impaired kidney transplant survival in patients with antibodies to hepatitis C virus.

BACKGROUND: With a few exceptions, most published studies do not show an influence of antibodies to the hepatitis C virus (HCV) on the success of a kidney transplant. METHODS: We studied all our renal transplant recipients who had received kidneys from cadaver donors (n = 335) and had been treated with quadruple immunosuppression (steroids, azathioprine, and antilymphocyte antibodies, followed by cyclosporin). We had information on the status of the hepatitis C antibodies before and/or after the transplant in 320 cases (95.5%; in 300, pre-transplant). Patients with HCV antibodies before and/or after the transplant were considered to be HCV positive (HCV+). RESULTS: The HCV+ patients had more time in dialysis and a greater number of transfusions, hyperimmunized cases, and re-transplants. The evolution in the first post-transplant year was similar in both groups, but afterwards, the HCV+ patients had proteinuria more often as well as worse kidney function. The survival rate of the graft was significantly less in the HCV+ cases: 90.6, 68.3 and 51.0% at respectively 1, 5 and 10 years, compared with 91.5, 84.7 and 66.5% in HCV-patients (P<0.01). The patient survival rate was: 96.4, 87.0, and 71.9% in the HCV+ patients at 1, 5, and 10 years, compared with 98.2, 96.0 and 90.0% in the HCV- cases respectively (P<0.01). The differences remained the same in stratified studies according to time spent in dialysis or pre/post-transplant evolution of HCV antibodies, even when immunologically high-risk patients were excluded. In multivariant analysis, the presence of HCV antibodies acted as a independent prognostic factor for the survival of the kidney and the patient: 3.0 (1.8-5.0) and 3.1 (1.2-7.8) odds-ratio (95% of the confidence interval), respectively. The main cause of death among HCV+ patients was cardiovascular; there was no apparent increase in mortality rate due to infections or chronic liver disease. The loss of organs was mainly due to chronic nephropathy or death with a functioning kidney. CONCLUSION: The presence of hepatitis C antibodies, before or after transplantation, is associated with a worse long-term survival rate for both the patient and the transplanted kidney in our patients treated with quadruple therapy.

Adult↗
PubMed1998

Continuous intravenous intradialysis versus intravenous postdialysis erythropoietin therapy in chronic haemodialysis patients: a randomized, controlled, crossover study.

BACKGROUND: Subcutaneous recombinant human erythropoietin seems to be more effective than intravenous administration. Local pain, however, may diminish patient compliance with the subcutaneous route. Recently continuous intravenous intradialysis administration of rHuEpo has been reported to be more efficacious in stimulating erythropoiesis than the usual postdialysis intravenous bolus. METHODS: We conducted a randomized, controlled, crossover study on stable chronic haemodialysis patients to compare the efficacy of continuous intradialysis rHuEpo therapy with intravenous postdialysis administration. Twenty patients were selected and randomly assigned to receive rHuEpo either postdialysis (control phase) or by continuous intradialysis perfusion (slow Epo phase) for 12 weeks. After this period, patients were switched to the alternative method for 12 additional weeks. The erythropoietin dose remained unchanged during the study. Haematocrit was monitored weekly and iron metabolism, serum Epo, and vitamins were measured monthly. Urea kinetics and iPTH measurements were performed every 3 months. RESULTS: Three patients were excluded because of unrelated problems. The final mean haematocrit was unchanged from previous basal values in both phases and no statistical differences were found for any parameter between the groups. No differences were found in iron metabolism nor in urea kinetic parameters. CONCLUSIONS: Continuous intravenous intradialysis administration of rHuEpo is not more effective than an intravenous postdialysis bolus as rHuEpo maintenance therapy in stable chronic haemodialysis patients.

Adolescent↗
PubMed1998

Blood groups and milk and type traits in dairy cattle: after forty years of research.

This study addresses the utility of 11 blood groups as selection aids in Holstein breeding schemes and considers issues inherent to the approach of resolving quantitative variation into components that are due to quantitative trait loci. The data consisted of predicted transmitting abilities of 22,614 bulls, first lactation information on 1,924,171 cows, and type scores on 447,800 cows. Linear models were fitted under male half-sib designs, female half-sib designs, and granddaughter designs as well as under the assumption of direct effects of the markers. The evolution of allele frequencies through time was determined, and previous research results were synthesized according to criteria of consistency of biological significance. The inconsistency of results across studies and analytical designs alludes to the importance of the intrinsic nonadditivity of genetic and biological phenomena to quantitative trait locus detection and marker-assisted selection. In our analyses, three associations met the criteria of consistency--a C blood group effect on rump angle, an L effect on milk yield and composition traits, and an S effect on milk fat yield. The M locus appears to be directly associated with effects on milk and protein yields. An enhanced understanding of the biochemical and physiological bases of quantitative genetics should be a long-term objective of this type of genetic analysis.

Animals↗
PubMed1998

Trait-based analysis in dairy cattle using blood group polymorphisms.

The potential of trait-based analysis to detect quantitative trait loci was investigated using blood group polymorphisms as the marker systems and milk and type traits in Holstein cattle as the quantitative traits. Within large half-sib families, animals were ranked on their predicted transmitted abilities or phenotypes, and blood group allele frequencies were compared between the upper and lower 5% tails of the distributions. Genotype frequencies within large families were also examined for evidence of selection. All of the major effects that had previously been detected using linear model analyses were identified by the trait-based analyses of a C blood group effect on rump angle, an L effect on milk yield and composition traits, an S effect on milk fat yield, and a direct effect of the M locus on milk and protein yields. These results provide additional support for the biological validity of these associations and also demonstrate the utility of trait-based analysis for the detection of quantitative trait loci within existing dairy breeding programs. However, just as in the linear model analyses, an analytical strategy should be utilized that allows the identification of the effects that are consistent across environments and genetic backgrounds.

Alleles↗
PubMed1997

A novel polymorphism in the coding region of the vasopressin type 2 receptor gene.

Nephrogenic diabetes insipidus (NDI) is a rare disease characterized by renal inability to respond properly to arginine vasopressin due to mutations in the vasopressin type 2 receptor (V2(R)) gene in affected kindreds. In most kindreds thus far reported, the mode of inheritance follows an X chromosome-linked recessive pattern although autosomal-dominant and autosomal-recessive modes of inheritance have also been described. Studies demonstrating mutations in the V2(R) gene in affected kindreds that modify the receptor structure, resulting in a dys- or nonfunctional receptor have been described, but phenotypically indistinguishable NDI patients with a structurally normal V2(R) gene have also been reported. In the present study, we analyzed exon 3 of the V2(R) gene in 20 unrelated individuals by direct sequencing. A C-->T alteration in the third position of codon 331 (AGC-->AGT), which did not alter the encoded amino acid, was found in nine individuals, including two unrelated patients with NDI. Taken together, these observations emphasize the molecular heterogeneity of a phenotypically homogeneous syndrome.

Diabetes Insipidus, Nephrogenic↗
PubMed1996

Sporadic cardiac myxomas and tumors from patients with Carney complex are not associated with activating mutations of the Gs alpha gene.

Cardiac myxomas are rare tumors that may be encountered sporadically or in the context of the Carney complex. The molecular basis for the development of cardiac myxomas and Carney complex tumors is unclear. Pathological myocardial function and myocardial hypertrophy have been associated with alterations in the heterotrimeric GTP-binding proteins. The postulated proto-oncogenic character of the gene encoding the alpha sub-unit of the stimulatory GTP-binding protein Gs alpha (gsp) in pituitary and thyroid tumors, the finding of identical somatic gsp mutations in the myocardium of patients with McCune-Albright syndrome, and the associated endocrine anomalies of the Carney complex prompted us to investigate the occurrence of activating missense mutations in the Gs alpha gene in 10 sporadically occurring atrial myxomas and in 8 tumors from 7 patients with Carney complex. No gsp mutations could be demonstrated by using the polymerase chain reaction and denaturing gradient gel electrophoresis complemented by direct DNA sequencing. Thus, activating Gs alpha mutations neither are associated with the development of atrial myxomas, nor can be demonstrated in other tumors from patients with Carney complex. The significance of these mutations in the myocardium of asymptomatic patients with McCune-Albright syndrome remains to be determined.

Adult↗
PubMed1992

Interaction of parasitism and nutrition in goats: effects on haematological parameters, correlations, and other statistical associations.

Weaned wether goats (n = 144) approximately 6 months of age were placed in a 2 x 3 factorial experiment to test the effects and interaction of two levels of nutrition (growth+maintenance, NUT1; and twice growth+maintenance, NUT2) and three levels of Haemonchus contortus burden (0, 500, and 2000 larvae administered every 2 weeks; W0, W500, and W2000, respectively) on packed cell volume, red blood cell count, total serum protein and leukocytes. The statistical analysis revealed clear and proportionate differences among levels of infection for all variables. A significant (P < 0.05) nutritional effect was also found associated with all the variables except leukocytes. Nutrition by worm load interactions were found for packed cell volume and leukocytes. The neutrophil/lymphocyte ratio was higher in the NUT1-infected animals, leading to the nutrition by worm load interaction for leukocytes. An analysis for the different leukocyte types revealed significant (P < 0.05) differences among infection levels for lymphocytes, while nutrition level was found to be a significant effect for basophil count and immature white cells. Several significant correlations were observed between pairs of variables. Faecal egg output could be predicted from actual worm count in three of the four necropsy periods. The clear differences observed for blood parameters were not present in production traits, suggesting that physiological thresholds may play an important role in framing the metabolic activity of biological organisms. Total serum protein was the best indicator of these effects on production parameters.

Animal Feed↗
PubMed1992

Statistical associations between restriction fragment length polymorphisms and quantitative traits in beef cattle.

Data on 41 traits from 677 animals produced in a five-breed diallel were matched with genotypes for five marker-loci provided by restriction fragment length polymorphisms to detect quantitative effects associated with the markers, following three different designs based on inbred lines, half-sib families, and on assumptions of the markers being quantitative trait loci (QTL). Three growth hormone-TaqI alleles, B, C, and D, in high frequencies in this sample of the Brahman breed, were associated with decreases in birth weight, as a maternal trait (P < .01), and decreases in shoulder width at birth (P < .05). Among F2 Angus-Brahman and Brahman-Hereford cows, homozygotes for the B, C, or D alleles gave birth to calves 4.0 kg lighter than cows homozygous for the A allele, an effect that amounts to the magnitude of the corresponding breed difference in the diallel, and represents one phenotypic SD. A putative cytoplasmic effect seems to interact (P = .02) with this effect on maternal birth weight. Also, at birth, F2 calves homozygous for the B, C, or D alleles were .8 cm narrower at the shoulders than those homozygous for the A allele, after adjusting for birth weight. Significant associations (P < .05) between the parathyroid hormone-MspI marker and measures of body size were detected, as well as an effect on weaning weight (P = .03) as a maternal trait, whose magnitude (17.5 kg) equals the Brahman vs Angus and Hereford breed difference, as quantified in the diallel, and represents .8 of a phenotypic SD. No significant associations were found for three other marker-loci (prolactin-MspI, osteonectin-EcoRI, and keratin VI-MspI). Restriction fragment length polymorphisms have the potential to provide new insights and useful applications to animal breeding, but, as in this work, small sample sizes, extreme susceptibility to Type I errors, and different types of possible confounding obfuscate the conclusions that can be drawn from studies of limited scope and less than ideal planning.

Alleles↗
PubMed1991

Interaction of parasitism and nutrition and their effects on production and clinical parameters in goats.

Weaned wether goats (n = 144) approximately 6 months of age were placed in a 2 x 3 factorial design experiment for 5 months to test the main effects and interaction of two levels of nutrition (growth + maintenance, NUT1; twice growth + maintenance, NUT2) and three levels of Haemonchus contortus burden (0, 500 and 2000 larvae administered every 2 weeks: W0, W500 W2000, respectively) on weight, feed intake, level of infection and packed cell volume (PCV). The rationale for the experimental design was based on the lack of information concerning the interaction between nutritional status and worm burden. Results indicated significant effects of worm burden levels on PCV, faecal egg contents (eggs per gram of feces (EPG)), actual worm numbers, feed intake and efficiency of feed utilization. Nutrition x worm burden interactions were also significant for PCV and EPG. However, the differences detected for PCV and actual worm numbers did not translate into large or consistent differences in body weight. Goats on NUT2, after an initial period, showed little difference in body weight, irrespective of worm burden. Within the NUT1 level, W0 kids weighed more than W500 or W2000 kids throughout the study. Although not statistically significant, this constitutes a trend towards an interaction between nutrition and worm burden. In both nutrition levels, there were no body weight differences between W500 and W2000 until the last 14 days. Feed intake was depressed in the first 3 months of the experiment for infected animals, but was subsequently followed by a compensatory reaction. Lower establishment rates, based on actual worm counts, were observed for the higher infection level, but in both infection levels establishment rates tended to decrease with time. Nutrition was found to be more important to counteract the consequences of a parasitic infection than to counteract the establishment of that same infection.

Animal Nutritional Physiological Phenomena↗
PubMed1990

Evaluation of the pituitary-adrenal axis before, during and after pituitary adenomectomy. Is perioperative glucocorticoid therapy necessary?

Under the supposition that ACTH secretion will be compromised by surgical trauma, patients with pituitary adenomas undergoing transsphenoidal adenomectomy are frequently given corticoids, even though this therapy is controversial. We studied 10 patients with pituitary adenomas whose adrenocortical function was sufficient prior to surgery. The ACTH and cortisol levels rose significantly during surgery in all of these patients. Five patients completed a two-year postoperative follow-up period and their ACTH and cortisol values remained within normal limits. It may be that patients undergoing transsphenoidal surgery for pituitary adenomas do not need perioperative glucocorticoid treatment, since the hypophyseal-adrenal axis does retain its integrity.

Adenoma↗