Biomedical subjects

C Reyes

Publications and source records attributed to C Reyes.

At least 19 recordsLinked to original sources

PubMed2001

Substance P immunoreactivity in the enteric nervous system in Rett syndrome.

Rett syndrome is associated with profound mental retardation and motor disability in girls. It has a characteristic clinical phenotype which includes abnormalities of the autonomic nervous system. Feeding impairment and severe constipation are two symptoms of this autonomic dysfunction. Substance P, an important peptide in the autonomic nervous system, is decreased in the cerebrospinal fluid of Rett syndrome. We have demonstrated that substance P immunoreactivity is significantly decreased in Rett syndrome brain-stem and may be related to the autonomic dysfunction. In this study, we have continued the investigation of substance P in the enteric nervous system. We immunohistochemically examined the normal developing bowel in 22 controls (ages, 14 gestational weeks to 31 years) using formalin fixed tissue, with antibodies to substance P, tyrosine hydroxylase and vasoactive intestinal peptide. We compared the immunoreactivity of normal controls with 14 cases of Rett syndrome (ages, 5-41 years) and observed that the expression of substance P, tyrosine hydroxylase and vasoactive intestinal peptide immunoreactivity in the bowel in Rett syndrome was not significantly different from that of controls. This suggests that the feeding impairment and constipation in Rett syndrome relate to dysfunction of the autonomic nervous system originating outside of the bowel, in the brain-stem, as suggested by our previous study.

Adolescent↗

PubMed2000

A first high-density map of 981 biallelic markers on human chromosome 14.

As the largest set of sequence variants, single-nucleotide polymorphisms (SNPs) constitute powerful assets for mapping genes and mutations related to common diseases and for pharmacogenetic studies. A major goal in human genetics is to establish a high-density map of the genome containing several hundred thousand SNPs. Here we assayed 3.7 Mb (154,397 bp in 24 alleles) of chromosome 14 expressed sequence tags (ESTs) and sequence-tagged sites, for sequence variation in DNA samples from 12 African individuals. We identified and mapped 480 biallelic markers (459 SNPs and 21 small insertions and deletions), equally distributed between EST and non-EST classes. Extensive research in public databases also yielded 604 chromosome 14 SNPs (dbSNPs), 520 of which could be mapped and 19 of which are common between CNG (i.e., identified at the Centre National de Génotypage) and dbSNP polymorphisms. We present a dense map of SNP variation of human chromosome 14 based on 981 nonredundant biallelic markers present among 1345 radiation hybrid mapped sequence objects. Next, bioinformatic tools allowed 945 significant sequence alignments to chromosome 14 contigs, giving the precise chromosome sequence position for 70% of the mapped sequences and SNPs. In addition, these tools also permitted the identification and mapping of 273 SNPs in 159 known genes. The availability of this SNP map will permit a wide range of genetic studies on a complete chromosome. The recognition of 45 genes with multiple SNPs, by allowing the construction of haplotypes, should facilitate pharmacogenetic studies in the corresponding regions.

Alleles↗

PubMed2000

Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models.

A historical perspective on the application of molecular dynamics (MD) to biological macromolecules is presented. Recent developments combining state-of-the-art force fields with continuum solvation calculations have allowed us to reach the fourth era of MD applications in which one can often derive both accurate structure and accurate relative free energies from molecular dynamics trajectories. We illustrate such applications on nucleic acid duplexes, RNA hairpins, protein folding trajectories, and protein-ligand, protein-protein, and protein-nucleic acid interactions.

Base Sequence↗

PubMed2000

Does perchlorate in drinking water affect thyroid function in newborns or school-age children?

Perchlorate is known to suppress thyroid function by inhibiting uptake of iodide by the human thyroid at doses of 200 mg/day or greater. A study was conducted to investigate the potential effects of perchlorate in drinking water on thyroid function in newborns and school-age children. A total of 162 school-age children and 9784 newborns were studied in three proximate cities in northern Chile that have different concentrations of perchlorate in drinking water: Taltal (100 to 120 micrograms/L), Chañaral (5 to 7 micrograms/L), and Antofagasta (non-detectable: < 4 micrograms/L). Among schoolchildren, no difference was found in thyroid-stimulating hormone levels or goiter prevalence among lifelong residents of Taltal or Chañaral compared with those of Antofagasta, after adjusting for age, sex, and urinary iodine. No presumptive cases of congenital hypothyroidism were detected in Taltal or Chañaral; seven cases were detected in Antofagasta. Neonatal thyroid-stimulating hormone levels were significantly lower in Taltal compared with Antofagasta; this is opposite to the known pharmacological effect of perchlorate, and the magnitude of difference did not seem to be clinically significant. These findings do not support the hypothesis that perchlorate in drinking water at concentrations as high as 100 to 120 micrograms/L suppresses thyroid function in newborns or school-age children.

Age Distribution↗

PubMed1999

Linkage analysis of candidate myelin genes in familial multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system. A complex genetic etiology is thought to underlie susceptibility to this disease. The present study was designed to analyze whether differences in genes that encode myelin proteins influence susceptibility to MS. We performed linkage analysis of MS to markers in chromosomal regions that include the genes encoding myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMGP), and myelin oligodendrocyte glycoprotein (MOG) in a well-characterized population of 65 multiplex MS families consisting of 399 total individuals, 169 affected with MS and 102 affected sibpairs. Physical mapping data permitted placement of MAG and PLP genes on the Genethon genetic map; all other genes were mapped on the Genethon genetic map by linkage analysis. For each gene, at least one marker within the gene and/or two tightly linked flanking markers were analyzed. Marker data analysis employed a combination of genetic trait model-dependent (parametric) and model-independent linkage methods. Results indicate that MAG, MBP, OMGP, and PLP genes do not have a significant genetic effect on susceptibility to MS in this population. As MOG resides within the MHC, a potential role of the MOG gene could not be excluded.

DNA Primers↗

PubMed1998

Delayed repair of congenital diaphragmatic hernia with early high-frequency oscillatory ventilation during preoperative stabilization.

PURPOSE: The authors reviewed their experience in the management of CDH after the introduction of early high-frequency oscillatory ventilation (HFOV) during the preoperative stabilization period and delayed CDH repair. METHODS: This is a retrospective analysis of 24 consecutive infants with CDH treated at University of California, Irvine Medical Center (UCIMC) during a 36-month period from January 1993 to December 1996. RESULTS: Two patients were excluded from the study: one fetus with a prenatal diagnosis was referred for fetal surgery; one infant received CDH repair at another institution 2 weeks before transfer to UCIMC. Eight (36%) infants were inborn, and nine (41%) had a prenatal diagnosis of CDH. Median gestational age was 40 weeks (range, 29 to 42 weeks). Median birth weight was 3,019 g (range, 1,205 to 4,337 g). The defect was left sided in 18 infants (86%). Twenty-one infants were intubated within 5 hours of life, 15 had an AaDO2 greater than 610, 11 had an oxygenation index greater than 40, and 11 had a pH of less than 7.2. The median ratio of pulmonary artery pressure to systemic blood pressure was 0.93 (range, 0.51 to 1.15) in 12 infants. Eighteen infants were placed on HFOV within a median of 1 hour of life. Nitric oxide was given to six infants and surfactant to eight. Four infants were referred for extracorporeal membrane oxygenation (ECMO). Repair of CDH was performed on infants at a median age of 33.5 hours (range, 5.5 to 322). Six (30%) received a prosthetic patch. Overall 18 of 22 infants survived (81%); three survivors received ECMO. Two infants of the survivor group had congenital heart anomalies: one ventricular septal defect (VSD) and one double-outlet right ventricle with a VSD. Of the four nonsurvivors, one had lethal cardiac anomalies and bilateral CDH, two had severe bilateral pulmonary hypoplasia (one received ECMO), and one infant was a 29-week premature baby who did not qualify for ECMO. CONCLUSION: We report a survival rate of 81% (18 of 22) with the management of CDH by delayed surgical repair, early postnatal HFOV, and selective referral for ECMO.

Extracorporeal Membrane Oxygenation↗

PubMed1998

Analysis of an activator:coactivator complex reveals an essential role for secondary structure in transcriptional activation.

Ser-133 phosphorylation of CREB within the kinase-inducible domain (KID) promotes target gene activation via complex formation with the KIX domain of the coactivator CBP. Concurrent phosphorylation of CREB at Ser-142 inhibits transcriptional induction via an unknown mechanism. Unstructured in the free state, KID folds into a helical structure upon binding to KIX. Using site-directed mutagenesis based on the NMR structure of the KID:KIX complex, we have examined the mechanisms by which Ser-133 and Ser-142 phosphorylation regulate CREB activity. Our results indicate that phospho-Ser-133 stablizes whereas phospho-Ser-142 disrupts secondary structure-mediated interactions between CREB and CBP. Thus, differential phosphorylation of CREB may form the basis by which upstream signals regulate the specificity of target gene activation.

Amino Acid Sequence↗

PubMed1997

A directional clustering technique for random data classification.

This paper introduces a new clustering technique for random data classification based on an enhanced version of the Voronoi diagram. This technique is optimized to deal in the best way possible with data distributions which in their spatial representations experience overlap. A mathematical framework is given in view of this enhanced analysis and provides insight to key issues involving (a) the use of a correction process to complement the traditional Voronoi diagram and (b) the introduction of directional vectors in Gaussian and elliptical data distributions for enhanced data clustering. The computational requirements of the proposed approach are provided, and the computer results involving both randomly generated and real-world data prove the soundness of this clustering technique.

Data Interpretation, Statistical↗

PubMed1997

Cytomegalovirus enteritis in a premature infant.

BACKGROUND/PURPOSE: Up to 2.5% of newborn infants are cytomegalovirus (CMV) positive at birth. Five percent will be symptomatic at birth, including cytomegalic inclusion disease. Symptoms such as hearing loss and mental retardation will ultimately develop in 15%. METHODS: The authors describe a case of CMV enteritis in a 2.2-kg newborn that presented as necrotizing enterocolitis (NEC) and subsequently developed a colonic stricture. RESULTS: There are four reports of neonatal CMV enteritis in the nonEnglish-language literature. Cytomegalovirus enteritis has become prevalent among the immunosuppressed pediatric and adult patient population. CONCLUSIONS: We propose the addition of CMV to the list of pathogens responsible for NEC. A review of neonatal CMV infection is provided.

Cytomegalovirus Infections↗

PubMed1997

Fetal lung maturation. Comparison of biochemical indices in gestational diabetic and nondiabetic pregnancies.

OBJECTIVE: To compare the biochemical maturation of the components of the lung profile according to gestational age between reliably dated gestational diabetic and nondiabetic pregnancies. STUDY DESIGN: Lung maturation was compared in reliably dated pregnancies in 501 gestational diabetic women and 561 nondiabetic women. Lecithin/sphingomyelin ratio (L/S) and phosphatidylglycerol (PG) were evaluated by analysis of variance according to the presence or absence of diabetes and weeks of gestational age. The effect of gestational diabetes on fetal lung maturation was determined by analysis of variance. RESULTS: The gestational diabetic group had no clinical or statistical differences in L/S ratios as compared to the nondiabetic patients at any gestational age. There were no differences in mean percent PG between the diabetic and nondiabetic groups at any gestational age. By 37 completed weeks, 86% of the L/S ratios and 78% of the PG values were mature in the diabetic group as compared to 80% of the L/S ratios and 78% of the PG values in the control group (P = .33 and .43, respectively). CONCLUSION: In reliably dated gestational diabetic pregnancies, biochemical maturation of the fetal lung strongly correlates with gestational age and does not appear to be significantly delayed when compared to a nondiabetic control group.

Adult↗

PubMed1996

A complete genomic screen for multiple sclerosis underscores a role for the major histocompatability complex. The Multiple Sclerosis Genetics Group.

Multiple sclerosis (MS), an inflammatory autoimmune demyelinating disorder of the central nervous system, is the most common cause of acquired neurological dysfunction arising in the second to fourth decades of life. A genetic component to MS is indicated by an increased relative risk of 20-40 to siblings compared to the general population (lambda s), and an increased concordance rate in monozygotic compared to dizygotic twins. Association and/or linkage studies to candidate genes have produced many reports of significant genetic effects including those for the major histocompatability complex (MHC; particularly the HLA-DR2 allele), immunoglobulin heavy chain (IgH), T-cell receptor (TCR) and myelin basic protein (MBP) loci. With the exception of the MHC, however, these results have been difficult to replicate and/or apply beyond isolated populations. We have therefore conducted a two-stage, multi-analytical genomic screen to identify genomic regions potentially harbouring MS susceptibility genes. We genotyped 443 markers and 19 such regions were identified. These included the MHC region on 6p, the only region with a consistently reported genetic effect. However, no single locus generated overwhelming evidence of linkage. Our results suggest that a multifactorial aetiology, including both environmental and multiple genetic factors of moderate effect, is more likely than an aetiology consisting of simple mendelian disease gene(s).

Chromosome Mapping↗

PubMed1996

Interactions among receptors, thyroid hormone response elements, and ligands in the regulation of the rat uncoupling protein gene expression by thyroid hormone.

Uncoupling protein (UCP) is essential to the thermogenic function of brown adipose tissue (BAT). Thyroid hormone stimulates the rat UCP gene through two thyroid hormone response elements (TRE) located upstream of -2,300 and separated by 27 bp. They are an everted repeat (upstream TRE or upTRE) and a direct repeat (down-stream TRE or dnTRE). The goal of the present studies was to investigate whether these TREs interact and how such an interaction could contribute to explain the UCP responsiveness to T3 in vivo. We therefore aimed to define: the heterodimeric partner of the T3 receptor (T3R); the role of T3 in the receptor-receptor and receptors-DNA interactions; how such in vitro interactions relate to the enhancer function of TREs; and how the two TREs interact. Studies included electrophoretic mobility shift assays, utilizing T3R and retinoid X receptors (RXR); DNA footprinting; and transient transfections of HIB-1B cells, a BAT-derived cell line. As in many previously described TREs, the partner of the T3R is RXR. The unliganded T3Rs bind to the TREs as homodimers, which act as repressors of transcription. T3 reduces the binding of T3R homodimers, hence relieving the repression, and stimulates the binding of heterodimers and transcription in proportion to the heterodimer binding to the elements. Although qualitatively similar in these regards, there were important quantitative differences between both TREs. The upTRE binds more T3R homodimers and less T3R-RXR heterodimers than the dnTRE, and T3 more readily facilitates heterodimer binding to the dn- than to the upTRE. These in vitro characteristics are reflected in a lower efficiency of T3 to relieve T3R homodimer-mediated repression and to stimulate transcription through up-than through dnTRE. There were also significant interactions between the two TREs both in the binding of the receptors, T3R and RXR, and in the responsiveness to T3. By itself, each TRE responded modestly to T3, upTRE with lower sensitivity and dnTRE with higher sensitivity than traditional TREs, whereas together, in the context of the gene sequence, they mediated a response greater than the sum of those mediated by each TRE separately, with an intermediate sensitivity to T3. Thus, two TREs that are inadequate to explain the responsiveness of the UCP gene to T3, together form a complex unit appropriate for the regulation of the gene by thyroid hormone. These interactions represent yet another way TREs can shape up the responsiveness of genes to thyroid hormone.

Adipocytes↗

PubMed1996

A complex retinoic acid response element in the uncoupling protein gene defines a novel role for retinoids in thermogenesis.

Retinoids have been implicated in the control of cell proliferation and differentiation, and in several developmental processes. We report here the molecular bases for a metabolic role of RA, by showing that the expression of the uncoupling protein (UCP), the key element in brown adipose tissue (BAT) thermogenesis, is stimulated by retinoic acid (RA). Both all-trans-RA and 9-cis-RA powerfully increase UCP messenger RNA levels in isolated rat brown adipocytes. Transient transfection experiments in HIB-1B cells, a BAT-derived cell line, identified the sequence -2399/-2490 (called R90) as the RA-responsive sequence in the rat UCP gene. R90 mediated a 20- to 70-fold stimulation of the chloramphenicol acetyl transferase reporter gene by maximal concentrations of all-trans-RA or 9-cis-RA. Non-BAT cells were significantly less responsive. RA effect was also less when chloramphenicol acetyl transferase gene was driven by a heterologous promoter instead of the UCP minimal promoter. By footprinting and site-directed mutagenesis, we identified three discrete sequences as being essential for the RA response within R90, thus defining the complex RA response element (RARE) of this gene. Critical bases in these sequences are arranged in pairs of putative half-sites. RAR gamma-RXR heterodimers can bind to the R90 as revealed by electrophoretic mobility shift assays using in vitro translated receptors, and HIB-1B nuclear extracts with anti-RAR gamma or anti-RXR antibodies. The participation of RAR gamma-RXR heterodimers in RA stimulation is further supported by transient transfection experiments overexpressing selected receptors and dose-response analyses of RA isomers and analogues. These results show that retinoids strongly stimulate the rat UCP gene expression through a complex RARE, composed of three pairs of half-sites, and define a novel role for retinoids in the regulation of facultative thermogenesis and energy expenditure.

Adipocytes↗

PubMed1994

Cytologic patterns of metastatic thymoma: diagnosis by fine-needle aspiration biopsy.

Thymomas are the most frequent primary tumors of the anterior mediastinum. These lesions are slow growing and can be locally invasive, but extrathoracic metastases are rare, occurring in less than 2% of cases. Fine-needle aspiration biopsy (FNAB) may be helpful in making the diagnosis of metastatic thymoma, with or without a clinical history of primary mediastinal thymoma. We report three cases of metastatic thymoma diagnosed by FNAB. Each case illustrates a distinctive cytologic pattern. While two of the patients had a history of histologically confirmed thymoma 11 and 13 years previously, a third patient presented with an enlarged supraclavicular lymph node and pulmonary nodules, and no prior diagnosis of thymoma. These cases demonstrate that based on distinctive cytologic patterns and features, a diagnosis of metastatic thymoma can be made with FNAB. Ancillary studies will often confirm the diagnosis.

Aged↗

PubMed1993

Hepatoid carcinoma of the stomach.

A patient with primary gastric carcinoma exhibiting hepatoid differentiation is described. The tumor itself was not associated with a high serum alpha-fetoprotein, but the cells stained positive for alpha-fetoprotein and alpha-1 antitrypsin. The patient underwent a total gastrectomy and wedge excision of the liver metastasis. The presence of metastatic hepatoid adenocarcinoma of the stomach should be considered in a patient who, during surgery for a primary gastric carcinoma, is found to have a liver metastasis that is diagnosed by frozen-section biopsy as a hepatoma. Because of lymph node and liver metastasis, prognosis appears to be poor for such patients.

Adenocarcinoma↗

PubMed1993

Simple technique for determination of the correct length of percutaneous tunnelled catheters in neonates and children.

A simple technique for determining the correct catheter length in percutaneous tunnelled catheters in infants and young children has been devised that virtually guarantees accurate catheter tip placement. Sixty-six patients, aged newborn to 5 years (mean, 1.6 years) have successfully undergone this technique. It is safe, simple, precise, quick, and cost effective. It requires only a hemostat, a suture, and the supplies provided in the prepackaged catheter kit. This technique should be used whenever a percutaneous technique for accessing the vein is used and fluoroscopy is available.

Anthropometry↗

PubMed1993

[Major adverse reactions to propylthiouracil in 586 cases of hyperthyroidism].

Aiming to know the incidence and evolution of major adverse reactions to propylthiouracil in patients with hyperthyroidism, we performed a retrospective analysis of 586 patients treated between 1982 and 1992. All known complications associated to the use of propylthiouracil were considered major adverse reactions, when other causes were discarded. Eight patients (1.4% of the sample) had major adverse reactions: three had agranulocytosis, 3 hepatitis, 1 cholestasis and 1 vasculitis. All had a good evolution after discontinuing the drug. The patients with agranulocytosis were treated with antibiotics and the patient with cholestasis received prednisone. We conclude that major adverse reactions to propylthiouracil are infrequent, that they occur preferentially during the first months of treatment, earlier after reexposure and that there was no associated mortality.

Adolescent↗

PubMed1992

Mycobacterium kansasii infection following primary pulmonary malignancy.

The purpose of this study was to determine whether any of the Mycobacterium kansasii cases were the consequences of primary lung malignancy. The records and chest x-ray films of 295 patients with M kansasii pulmonary infection were reviewed. The infection was found to complicate the primary lung neoplasm in four cases. Three patients had had treatment for malignancy: one patient with small cell carcinoma received chemotherapy, steroids and radiation; one with adenocarcinoma underwent a lobectomy and radiation; and the third patient had a lobectomy and radiation for malignant fibrohistiocytoma. The fourth patient developed the infection three years after lung malignancy manifested itself, which was only a few months before the clinical evidence of distant metastasis with adenocarcinoma was detected. We suggest that this infection be considered in patients from M kansasii endemic areas, especially after they have received radiation treatment for lung malignancy. This association has never been described before.

Humans↗