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Denia Ramirez-Montealegre

Publications and source records attributed to Denia Ramirez-Montealegre.

5 recordsLinked to original sources
PubMed2006

Standardized assessment of behavior and adaptive living skills in juvenile neuronal ceroid lipofuscinosis.

We obtained information about the behavioral, psychiatric, and functional status of 26 children (13 males, 13 females) with juvenile neuronal ceroid lipofuscinosis (JNCL; mean age 12y 3mo [SD 3y 4mo]; range 6y 9mo to 18y 8mo). Twenty-five children had visual impairment and 18 were known to have a positive seizure history before enrollment. Parents completed the Child Behavior Checklist, Scales of Independent Behavior - Revised, and a structured interview to assess obsessive-compulsive symptoms. Participants exhibited a broad range of behavioral and psychiatric problems, rated as occurring frequently and/or as severe in more than half of the sample. Males and females did not differ with regard to the number of behavioral and psychiatric problems. Children were also limited in their ability to perform activities of daily living, including self-care, hygiene, socialization, and other age-appropriate tasks. Results provide a quantitative baseline for behavioral and psychiatric problems and functional level in JNCL, against which further decline can be measured. Longitudinal assessment of behavioral and psychiatric symptoms and functional abilities is continuing and will provide much-needed data on the natural history of JNCL.

Activities of Daily Living↗
PubMed2005

Defective lysosomal arginine transport in juvenile Batten disease.

Mutations in the CLN3 gene, which encodes a lysosomal membrane protein, are responsible for the neurodegenerative disorder juvenile Batten disease. A previous study on the yeast homolog to CLN3, designated Btn1p, revealed a potential role for CLN3 in the transport of arginine into the yeast vacuole, the equivalent organelle to the mammalian lysosome. Lysosomes isolated from lymphoblast cell lines, established from individuals with juvenile Batten disease-bearing mutations in CLN3, but not age-matched controls, demonstrate defective transport of arginine. Furthermore, we show that there is a depletion of arginine in cells derived from individuals with juvenile Batten disease. We have, therefore, characterized lysosomal arginine transport in normal lysosomes and show that it is ATP-, v-ATPase- and cationic-dependent. This and previous studies have shown that both arginine and lysine are transported by the same transport system, designated system c. However, we report that lysosomes isolated from juvenile Batten disease lymphoblasts are only defective for arginine transport. These results suggest that the CLN3 defect in juvenile Batten disease may affect how intracellular levels of arginine are regulated or distributed throughout the cell. This assertion is supported by two other experimental approaches. First, an antibody to CLN3 can block lysosomal arginine transport and second, expression of CLN3 in JNCL cells using a lentiviral vector can restore lysosomal arginine transport. CLN3 may have a role in regulating intracellular levels of arginine possibly through control of the transport of this amino acid into lysosomes.

Adenosine Triphosphate↗
PubMed2004

Homogeneous polymerase chain reaction nucleobase quenching assay to detect the 1-kbp deletion in CLN3 that causes Batten disease.

Batten disease is an autosomal recessive disorder also known as juvenile neuronal ceroid lipofuscinosis. The most common mutation for this disease is an approximately 1-kbp deletion in the CLN3 gene, which accounts for about 80 to 85% of the mutation load. We developed a rapid assay for this mutation using the PCR to produce amplicons that are detected by nucleobase quenching of the fluorescent signal from a probe labeled with a fluorescent dye. The probe overlaps the deletion breakpoint and is completely base paired to the mutant amplicon. However, three bases at the 5' end of the probe do not base pair with the wild-type amplicon. The alleles are distinguished by the different melting temperatures of the probe amplicon hybrids. Comparison of this new method with an allele-specific PCR and gel electrophoresis-based method showed 100% concordance in determination of the genotype for 30 specimens (11 homozygous mutant, 8 heterozygotes, and 11 homozygous normal). PCR followed by allele-specific melting curve analysis using nucleobase quenching has utility as a rapid method for detection of the most common mutation that causes Batten disease.

Female↗
PubMed2003

A role in vacuolar arginine transport for yeast Btn1p and for human CLN3, the protein defective in Batten disease.

In Saccharomyces cerevisiae, transport of arginine into the vacuole has previously been shown to be facilitated by a putative H+/arginine antiport. We confirm that transport of arginine into isolated yeast vacuoles requires ATP and we demonstrate a requirement for a functional vacuolar H+-ATPase. We previously reported that deletion of BTN1 (btn1-delta), an ortholog of the human Batten disease gene CLN3, resulted in a decrease in vacuolar pH during early growth. We report that this altered vacuolar pH in btn1-delta strains underlies a lack of arginine transport into the vacuole, which results in a depletion of endogenous vacuolar arginine levels. This arginine transport defect in btn1-delta is complemented by expression of either BTN1 or the human CLN3 gene and strongly suggests a function for transport of, or regulation of the transport of, basic amino acids into the vacuole or lysosome for yeast Btn1p, and human CLN3 protein, respectively. We propose that defective transport at the lysosomal membrane caused by an absence of functional CLN3 is the primary biochemical defect that results in Batten disease.

Arginine↗