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J Sainz

Publications and source records attributed to J Sainz.

At least 19 recordsLinked to original sources
PubMed2004

Effects of deoxycorticosterone on renal vascular reactivity and flow-pressure curve in spontaneously hypertensive rats.

The role of mineralocorticoids as sodium retaining hormones has been recently enlarged to include their function as modulators of cardiovascular function and injury. This study evaluated the contribution of possible functional changes in resistance vessels to the additional BP increase produced by the chronic administration of DOCA to SHR. The flow-pressure curve and renal responses to vasoconstrictors (phenylephrine [Phe] and angiotensin II [AII]) and vasodilators (acetylcholine [ACh] and nitroprusside [NP]) were characterized in isolated kidneys from Wistar Kyoto (WKY) and SHR treated or untreated with DOCA for nine weeks. DOCA increased BP in SHR but did not modify BP in WKY rats. Kidneys from SHR showed enhanced reactivity to Phe and AII that was not increased by DOCA. DOCA reduced sensitivity to AII in SHR. Responsiveness to ACh was increased in SHR and was not attenuated by DOCA in WKY or SHR. Vasodilator response to NP was not significantly affected by DOCA in WKY or SHR. The flow-pressure curve was markedly up-shifted in SHR when compared with kidneys from WKY rats. DOCA administration did not modify the flow-pressure curve in WKY but produced attenuation at low flow levels in SHR. Our results demonstrate that DOCA increases BP in SHR but does not increase the flow-pressure curve or renal vascular reactivity to vasoconstrictors, and does not reduce responsiveness to endothelium-dependent and independent vasodilators in SHR or WKY rats. Therefore, our data suggest that the BP increase produced by DOCA in SHR is not related to abnormalities in vascular function in resistance vessels.

Acetylcholine↗
PubMed2000

Contribution of endothelium-derived relaxing factors to P2Y-purinoceptor-induced vasodilation in the isolated rat kidney.

We examined the role of endothelium-derived relaxing factors nitric oxide (NO), endothelium-derived hyperpolarising factor (EDHF), and prostaglandins (PGs) to P(2Y1)- and P(2Y2)-purinoceptor-induced vasodilation in isolated rat kidney. To do it, we analysed the renal response to ATP, 2-methylthio ATP, and UTP in rat renal vasculature under normal conditions and after the administration of: N(w)-nitro-L-arginine (L-NAME), increased K(+) concentration, indomethacin, and L-NAME and increased K(+) together. Our results indicate that the vasodilator response to P(2Y1)- and P(2Y2)-purinoceptor activation in the isolated perfused kidney of rats is subserved by EDHF and NO.

Animals↗
PubMed1999

Genetic locus heterogeneity in Lafora's progressive myoclonus epilepsy.

In 1995, we mapped a gene for Lafora's progressive myoclonus epilepsy in chromosome 6q23-25. In 1997 and 1998, we reduced the size of the locus to 300 kb, and an international collaboration identified mutations in the protein tyrosine phosphatase gene. Here, we examine for heterogeneity through the admixture test in 22 families and estimate the proportion of linked families to be 75 to 85%. Extremely low posterior probabilities of linkage (Wi), exclusionary LOD scores, and haplotypes identify 4 families unlikely to be linked to chromosome 6q24.

Chromosomes, Human, Pair 6↗
PubMed1999

Association of collagen type 1 alpha1 gene polymorphism with bone density in early childhood.

Osteoporosis is a disease characterized by the development of nontraumatic fractures, most commonly in the vertebrae of elderly women. Approximately 500,000 elderly women in the United States are newly diagnosed with vertebral fractures every year, as the compressive strength of the vertebra, mainly determined by the density of cancellous bone and its cross-sectional area, declines with age. A recent study in women suggested that a polymorphism in the Sp1 binding site of the collagen type I gene (COLIA1) was related to decreased vertebral bone mass and vertebral fractures. Determining the phenotypic trait(s) responsible for this relationship and whether this association is manifested in childhood would further define the structural basis for decreased bone mass and help identify children "at risk" for fractures later in life. We therefore studied the COLIA1 gene polymorphism and measurements of the size and the density of vertebral bone in 109 healthy, prepubertal girls. On average, 22 girls with the Ss genotype and one girl with the ss genotype had 6.7% and 49.4% lower cancellous bone density in the vertebrae than girls with the SS genotype. In contrast, there was no association between the size of the vertebrae and the COLIA1 genotypes.

Aging↗
PubMed1999

Mapping and positional cloning of common idiopathic generalized epilepsies: juvenile myoclonus epilepsy and childhood absence epilepsy.

Among the 40 to 100 million persons with epilepsy worldwide and the 2 to 2.5 million persons with epilepsies in the United States, approximately 50% have generalized epilepsies. Among all epilepsies, the most common are juvenile myoclonus epilepsy (JME) with 10% to 30% of cases, childhood absence epilepsy (CAE) with 5% to 15% of cases, and pure grand mal on awakening with 22% to 37% of cases. In the last decade, six different chromosomal loci for common generalized epilepsies have been identified. These include two separate loci for JME in chromosomes 6p and 15q. The epilepsy locus in chromosome 6p expresses the phenotypes of classic JME, pure grand mal on awakening, and possibly JME mixed with absences. Two separate loci also are present for pyknoleptic CAE, namely, CAE that evolves to JME in chromosome 1p and CAE with grand mal in chromosome 8q24. Pandolfo et al. from the Italian League Against Epilepsy have reported two other putative susceptibility loci for idiopathic generalized epilepsies, namely, grand mal and generalized spike waves 35l in chromosome 3p and generalized epilepsies with febrile convulsions, grand mal, JME, absences, and electroencephalographic spike waves in 8q24. This chapter reports on the debate concerning whether there may be two separate epilepsy loci in chromosome 6p, one in the HLA region and one below HLA. The chapter then discusses the progress made in our laboratories as a result of the Genetic Epilepsy Studies (GENES) International Consortium. We discuss (a) the 2 to 6 cM critical region for classic JME located some 20 cM below HLA in chromosome 6p, (b) the 7-cM area for pyknoleptic CAE that evolves to JME in chromosome 1p, and (c) the 3.2 cM area for pyknoleptic CAE with grand mal and irregular 3 to 4 Hz spike waves in chromosome 8q24. We discusses efforts underway to refine the genetic map of JME in chromosome 6p11 and the advances in physical mapping and positioning of candidate genes, such as the gamma-aminobutyric acid receptor gene, the potassium channel gene of the long-QT family (KvLQT), named KCNQ3, and the human homologue of the mouse jerky gene for CAE in chromosome 8q24 and JME in chromosome 6p11.

Chromosome Mapping↗
PubMed1998

[Gammography using Tc 99m MIBI in patients with suspected breast cancer. Proposed diagnostic protocol].

The aim of this work has been to determine whether the joint use of mammography and scintimammography is capable of reducing the number of biopsies required in patients with suspected breast cancer. We have performed scintimammography in 90 patients, 97 lesions, with breast cancer suspicion. In the mammography was evaluated the degree of malignancy suspicion and the size of the lesion. Only 41 of the biopsies revealed the presence of cancer. The sensitivity, specificity, PPV and NPV of scintimammography were 85%, 79%, 74% and 88%. According to the mammography findings 20 lesions (1 breast cancer) were included as low, 31 lesions (4 breast cancer) as indeterminate and 46 lesions (36 breast cancer) as high malignancy suspicion. 14 lesions (2 low, 2 indeterminate and 10 high suspicion) were smaller than 1 cm. The scintimammography was positive in all breast cancer of low and indeterminate suspicion of malignancy and in 30 of high probability. On the basis of this results we propose that a biopsy must be carried out to those lesions with a high suspicion of malignancy, and to lesions with low or indeterminate suspicion that are smaller than 1 cm or that present a positive scintimammography. Following this protocol, only 64 of the 97 biopsies would have been necessary, with a reduction of the 34% in the total number of biopsies and, more important, a 65% of reduction in the number of biopsies carried out in the groups of low and indeterminate suspicion of malignancy. At the same time we would indicate biopsy in all cases of breast cancer.

Adult↗
PubMed1997

Vitamin D-receptor gene polymorphisms and bone density in prepubertal American girls of Mexican descent.

BACKGROUND: Bone mass is under strong genetic control, and recent studies in adults have suggested that allelic differences in the gene for the vitamin D receptor may account for inherited variability in bone mass. We studied the relations of the vitamin D-receptor genotype to skeletal development and variation in the size, volume, and density of bone in children. METHODS: We identified three allelic variants of the vitamin D-receptor gene using the polymerase chain reaction and three restriction enzymes (ApaI, BsmI, and TaqI) in 100 normal prepubertal American girls of Mexican descent. We then determined the relations of the different vitamin D-receptor genotypes (AA, Aa, aa, BB, Bb, bb, TT, Tt, and tt) to the cross-sectional area, cortical area, and cortical bone density of the femoral shaft and the cross-sectional area and density of the lumbar vertebrae. RESULTS: The vitamin D-receptor genotype was associated with femoral and vertebral bone density. Girls with aa and bb genotypes had 2 to 3 percent higher femoral bone density (P=0.008 and P=0.04, respectively) and 8 to 10 percent higher vertebral bone density (P=0.01 and P=0.03, respectively) than girls with AA and BB genotypes. There was no association between the cross-sectional area of the vertebrae or the cross-sectional or cortical area of the femur and the vitamin D-receptor genotype. The chronologic age, bone age, height, weight, body-surface area, and body-mass index did not differ significantly among girls with different vitamin D-receptor genotypes. CONCLUSIONS: Vitamin D-receptor gene alleles predict the density of femoral and vertebral bone in prepubertal American girls of Mexican descent.

Alleles↗
PubMed1996

Identification of three neurofibromatosis type 2 (NF2) gene mutations in vestibular schwannomas.

Vestibular schwannomas (VSs) are common benign tumors of Schwann cell origin and are frequently found in patients with neurofibromatosis type 2 (NF2). We analyzed 15 sporadic VSs for mutations in the tumors, two of which contained loss of heterozygosity (LOH). One of the tumors contained a novel mutation, a 19-bp deletion in exon 4. The two other tumors contained an identical mutation, a complete exon 4 deletion. The exon 4 deletion represents the second most frequently reported mutation of the NF2 gene in VSs.

Chromosome Deletion↗
PubMed1996

Presymptomatic diagnosis of neurofibromatosis 2 using linked genetic markers, neuroimaging, and ocular examinations.

Neurofibromatosis 2 (NF2) is an autosomal dominant disorder that causes nervous system tumors and ocular abnormalities such as early-onset lenticular opacities. We assessed the clinical spectrum of NF2 at the time of presymptomatic DNA diagnosis in at-risk first-degree relatives. We studied five multigeneration NF2 families with short tandem repeat markers near the NF2 gene (NF2); gadolinium-enhanced high-resolution magnetic resonance imaging (GE-MRI); and ocular, dermatologic, and neurologic examinations. Eleven of 31 asymptomatic at-risk first-degree relatives were predicted by segregation analysis to be NF2 mutation carriers. Nine of the 11 NF2 mutation carriers were clinically evaluated. Four mutation carriers, including a 7-year-old, had vestibular schwannomas, early-onset cataracts, or both. However, five mutation carriers did not have clinical abnormalities, including a 38-year-old with normal cranial and spinal GE-MRIs and a normal ocular examination. These results indicate that clinical abnormalities can be present in young, but absent in middle-aged, presymptomatic NF2 mutation carriers. By identifying presymptomatic NF2 mutation carriers, DNA diagnosis of NF2 can improve genetic counseling and clinical management, and possibly reduce psychosocial difficulties in at-risk individuals.

Adult↗
PubMed1995

Construction and utility of a human chromosome 22-specific Fosmid library.

We have previously demonstrated the capability of the Fosmid vector based on Escherichia coli F-factor replicon to stably propagate cosmid-sized human genomic DNA fragments. Using the Fosmid vector, we have constructed and arrayed a 10 x human chromosome 22-specific library, partly by picking human positive clones from a total Fosmid library constructed using DNA from human-hamster hybrid cell line containing human chromosome 22, and partly by using flow-sorted chromosomal DNA. The clones and physical contig maps of the clones in the library will serve as a valuable resource for detailed analysis of the chromosome by providing reliable materials for high resolution mapping and sequencing. In order to efficiently build physical maps for the chromosomal regions of interest spanning several hundred kilobases to a megabase, it is necessary to rapidly identify subsets of the Fosmid clones from the library that cover such regions. In this report, we describe a method of using random amplification products derived from YAC clones to rapidly identify a subset of Fosmid clones that cover a specific genomic subregion.

Animals↗
PubMed1995

Ocular abnormalities in neurofibromatosis 2.

PURPOSE: To evaluate the ocular abnormalities in patients with clinically diagnosed neurofibromatosis 2 and asymptomatic gene carriers. METHODS: Probands were ascertained through a surgical otolaryngology practice. In a cross-sectional study, we examined 49 patients with neurofibromatosis 2, 30 offspring of patients, and, as a comparison group, 18 parents and siblings of patients with sporadic neurofibromatosis 2. The examination included a complete neuro-ophthalmic assessment, physical examination, and, for patients and first-degree relatives at risk, cranial and spinal magnetic resonance imaging with gadolinium enhancement, if not previously performed. RESULTS: The most common ocular abnormalities were posterior subcapsular or capsular, cortical, or mixed lens opacities in 33 (67%) of 49 patients with neurofibromatosis 2 and retinal hamartomas in 11 (22%). We used segregation analysis to determine the mutation carrier status of six at-risk offspring who were 30 years old or younger in two multigeneration families. Three asymptomatic mutation carriers had cataracts, whereas those who were predicted not to carry the mutation did not have cataracts. Asymptomatic mutation carriers may have developmental abnormalities of the eye that are detectable in childhood or adolescence, a finding that may assist in early diagnosis of the disease. CONCLUSIONS: A variety of ocular abnormalities are present in neurofibromatosis 2, including cataracts, retinal hamartomas, and ocular motor deficits. Many of these are developmental or acquired early in life and may assist in presymptomatic diagnosis. For screening at-risk relatives of patients with neurofibromatosis 2, the types of cataract that are most suggestive of neurofibromatosis 2 are plaque-like posterior subcapsular or capsular cataract and cortical cataract with onset under the age of 30 years.

Adolescent↗
PubMed1994

Mutations of the neurofibromatosis type 2 gene and lack of the gene product in vestibular schwannomas.

Schwannomas are common tumors of the nervous system and are frequently found in patients with neurofibromatosis (NF) 2. Although loss of heterozygosity in NF2 tumors suggests that the NF2 gene functions as a tumor suppressor gene, the NF2 gene shows amino acid sequence homology to structural proteins in one of which dominantly acting mutations have been described. We performed a mutational analysis in 30 vestibular schwannomas and examined the effect of mutations on the NF2 protein. We detected 18 mutations in 30 vestibular schwannomas of which seven contained loss or mutation of both NF2 alleles. Most mutations were predicted to result in a truncated protein. Mutational hot spots were not identified. Immunocytochemical studies using antibodies to the NF2 protein showed complete absence of staining in tumor Schwann cells, whereas staining was observed in normal vestibular nerve. These data indicate that loss of NF2 protein function is a necessary step in schwannoma pathogenesis and that the NF2 gene functions as a recessive tumor suppressor gene.

Amino Acid Sequence↗