Biomedical subjects

Julie Park

Publications and source records attributed to Julie Park.

10 recordsLinked to original sources

PubMed2006

Genome Snapshot: a new resource at the Saccharomyces Genome Database (SGD) presenting an overview of the Saccharomyces cerevisiae genome.

Sequencing and annotation of the entire Saccharomyces cerevisiae genome has made it possible to gain a genome-wide perspective on yeast genes and gene products. To make this information available on an ongoing basis, the Saccharomyces Genome Database (SGD) (http://www.yeastgenome.org/) has created the Genome Snapshot (http://db.yeastgenome.org/cgi-bin/genomeSnapShot.pl). The Genome Snapshot summarizes the current state of knowledge about the genes and chromosomal features of S.cerevisiae. The information is organized into two categories: (i) number of each type of chromosomal feature annotated in the genome and (ii) number and distribution of genes annotated to Gene Ontology terms. Detailed lists are accessible through SGD's Advanced Search tool (http://db.yeastgenome.org/cgi-bin/search/featureSearch), and all the data presented on this page are available from the SGD ftp site (ftp://ftp.yeastgenome.org/yeast/).

Chromosomes, Fungal↗

PubMed2006

Strain-specific differences in two large Mycobacterium tuberculosis genotype clusters in isolates collected from homeless patients in New York City from 2001 to 2004.

We studied two large Mycobacterium tuberculosis genotype clusters associated with recent outbreaks in homeless persons to determine factors associated with these tuberculosis (TB) strains. Isolates from all culture-positive TB cases diagnosed from 1 January 2001 to 31 December 2004 were genotyped. Patients whose isolates had identical restriction fragment length polymorphism patterns and spoligotypes were considered clustered. Health department records were reviewed and reinterviews attempted for clustered cases. Patients with the Cs30 and BEs75 strains were compared to other genotypically clustered cases and to each other. The two largest genotype clusters among homeless persons were the Cs30 strain (n = 105) and the BEs75 strain (n = 47). Fifty-one (49%) patients with the Cs30 strain and 28 (60%) with the BEs75 strain were homeless. Compared to patients with the BEs75 strain, patients with the Cs30 strain were less likely to be respiratory acid-fast bacillus smear positive (51% versus 72%). Furthermore, patients with the BEs75 strain were more likely to be HIV infected (74% versus 42%), which suggests that most patients with this strain advanced to disease after recent infection. Cases in clusters of strains that have been circulating in the community over a long time period, such as the Cs30 strain, require additional investigation to determine whether clustering is a result of recent transmission or reactivation of remote infection.

Adolescent↗

PubMed2005

Response.

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Child↗

PubMed2004

Mutational analysis of the N-terminal DNA-binding domain of sleeping beauty transposase: critical residues for DNA binding and hyperactivity in mammalian cells.

The N-terminal domain of the Sleeping Beauty (SB) transposase mediates transposon DNA binding, subunit multimerization, and nuclear translocation in vertebrate cells. For this report, we studied the relative contributions of 95 different residues within this multifunctional domain by large-scale mutational analysis. We found that each of four amino acids (leucine 25, arginine 36, isoleucine 42, and glycine 59) contributes to DNA binding in the context of the N-terminal 123 amino acids of SB transposase, as indicated by electrophoretic mobility shift analysis, and to functional activity of the full-length transposase, as determined by a quantitative HeLa cell-based transposition assay. Moreover, we show that amino acid substitutions within either the putative oligomerization domain (L11A, L18A, L25A, and L32A) or the nuclear localization signal (K104A and R105A) severely impair its ability to mediate DNA transposition in mammalian cells. In contrast, each of 10 single amino acid changes within the bipartite DNA-binding domain is shown to greatly enhance SB's transpositional activity in mammalian cells. These hyperactive mutations functioned synergistically when combined and are shown to significantly improve transposase affinity for transposon end sequences. Finally, we show that enhanced DNA-binding activity results in improved cleavage kinetics, increased SB element mobilization from host cell chromosomes, and dramatically improved gene transfer capabilities of SB in vivo in mice. These studies provide important insights into vertebrate transposon biology and indicate that Sleeping Beauty can be readily improved for enhanced genetic research applications in mammals.

Amino Acid Sequence↗

PubMed2003

Oncogenic targeting of an activated tyrosine kinase to the Golgi apparatus in a glioblastoma.

Activating oncogenic mutations of receptor tyrosine kinases (RTKs) have been reported in several types of cancers. In many cases, genomic rearrangements lead to the fusion of unrelated genes to the DNA coding for the kinase domain of RTKs. All RTK-derived fusion proteins reported so far display oligomerization sequences within the 5' fusion partners that are responsible for oncogenic activation. Here, we report a mechanism by which an altered RTK gains oncogenic potential in a glioblastoma cell line. A microdeletion on 6q21 results in the fusion of FIG, a gene coding for a Golgi apparatus-associated protein, to the kinase domain of the protooncogene c-ROS. The fused protein product FIG-ROS is a potent oncogene, and its transforming potential resides in its ability to interact with and become localized to the Golgi apparatus. Thus we have found a RTK fusion protein whose subcellular location leads to constitutive kinase activation and results in oncogenic transformation.

Animals↗

PubMed2003

Fusion of FIG to the receptor tyrosine kinase ROS in a glioblastoma with an interstitial del(6)(q21q21).

The transmembrane proto-oncogene receptor tyrosine kinase (RTK) ROS is an orphan receptor that is aberrantly expressed in neoplasms of the central nervous system. Here, we report the fusion of its carboxy-terminal kinase domain to the amino-terminal portion of a protein called FIG (Fused in Glioblastoma) in a human glioblastoma multiforme (GBM). By characterizing both FIG and ROS genes in normal and in U118MG GBM cells, we determined that an intra-chromosomal homozygous deletion of 240 kilobases on 6q21 is responsible for the formation of the FIG-ROS locus. The FIG-ROS transcript is encoded by 7 FIG exons and 9 ROS-derived exons. We also demonstrate that the FIG-ROS locus encodes for an in-frame fusion protein with a constitutively active kinase activity, suggesting that FIG-ROS may act as an oncogene. This is the first example of a fusion RTK protein that results from an intra-chromosomal deletion, and it represents the first fusion RTK protein isolated from a human astrocytoma.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Clinical and molecular study in congenital muscular dystrophy with partial laminin alpha 2 (LAMA2) deficiency.

Complete laminin alpha2 (LAMA2) deficiency causes approximately half of congenital muscular dystrophy (CMD) cases. Many loss-of-function mutations have been reported in these severe, neonatal-onset patients, but only single missense mutations have been found in milder CMD with partial laminin alpha2 deficiency. Here, we studied nine patients diagnosed with CMD who showed abnormal white-matter signal at brain MRI and partial deficiency of laminin alpha2 on immunofluorescence of muscle biopsy. We screened the entire 9.5 kb laminin alpha2 mRNA from patient muscle biopsy by direct capillary automated sequencing, single strand conformational polymorphism (SSCP), or denaturing high performance liquid chromatography (DHPLC) of overlapping RT-PCR products followed by direct sequencing of heteroduplexes. We identified laminin alpha2 sequence changes in six of nine CMD patients. Each of the gene changes identified, except one, was novel, including three missense changes and two splice-site mutations. The finding of partial laminin alpha2 deficiency by immunostaining is not specific for laminin alpha2 gene mutation carriers, with only two patients (22%) showing clear causative mutations, and an additional three patients (33%) showing possible mutations. The clinical presentation and disease progression was homogeneous in the laminin alpha2-mutation positive and negative CMD patients.

Clubfoot↗

PubMed2003

Treatment of neuroblastoma in patients with neurocristopathy syndromes.

Neuroblastoma, a neoplasm of neural crest cell origin, occasionally presents in association with other neural crest abnormalities such as Hirschsprung disease, congenital central hypoventilation, autonomic disturbances, and other tumors. These associations have been termed "neurocristopathy syndromes." In the past, chemotherapy has not been considered for patients with neurocristopathy-associated neuroblastoma because of their complicated medical problems. The authors describe two patients with neurocristopathy syndromes from our institution who underwent surgery and standard chemotherapy treatment of their intermediate-risk neuroblastoma. They represent two of only three long-term disease-free survivors of neurocristopathy-associated neuroblastoma reported in the literature.

Abnormalities, Multiple↗

PubMed2003

Inclusion of immigrant status in smoking prevalence statistics.

OBJECTIVES: Data from the 1995-1996 and 1998-1999 Current Population Survey tobacco use supplements were used to examine smoking prevalence statistics by race/ethnicity and immigrant status. METHODS: Smoking prevalence statistics were calculated, and these data were decomposed by country of birth for Asian immigrants to illustrate the heterogeneity in smoking rates present within racial/ethnic groups. RESULTS: Except in the case of male Asian/Pacific Islanders, immigrants exhibited significantly lower smoking prevalence rates than nonimmigrants. However, rates varied according to country of birth. CONCLUSIONS: This research highlights the need to disaggregate health statistics by race/ethnicity, sex, immigrant status, and, among immigrants, country of birth. Data on immigrants' health behaviors enhance the development of targeted and culturally sensitive public health smoking prevention programs.

Adolescent↗

PubMed2002

Peripheral blood stem cell support reduces the toxicity of intensive chemotherapy for children and adolescents with metastatic sarcomas.

BACKGROUND: To increase the dose intensity (DI) of chemotherapy for pediatric patients with metastatic sarcomas, including the Ewing sarcoma family of tumors (ESFT) and rhabdomyosarcoma (RMS), the authors tested the feasibility of an intensive regimen supported by granulocyte-colony stimulating factor (G-CSF) and peripheral blood stem cells (PBSC). METHODS: Twenty-three children and adolescents with metastatic sarcomas received vincristine, doxorubicin, cyclophosphamide, ifosfamide, sodium mercaptoethanesulfonate (mensa), and etoposide (VACIME) chemotherapy, consisting of 8 courses of vincristine 2 mg/m(2) on Day 0, doxorubicin 37.5 mg/m(2) per day on Days 0-1, cyclophosphamide 360 mg/m(2) per day on Days 0-4, ifosfamide 1800 mg/m(2) per day on Days 0-4, mesna 2400 mg/m(2) per day, and etoposide 100 mg/m(2) per day on Days 0-4. Doxorubicin was omitted in Courses 7 and 8. G-CSF was given after each course of therapy. Courses of therapy were repeated every 21 days or as soon as hematopoietic recovery permitted. PBSC were collected twice: first, after Course 2 (infused after Courses 3 and 4) and, second, after Course 4 (infused after Courses 5 and 6). Surgical resection followed Course 6, and radiotherapy followed Course 8. RESULTS: PBSC collections were adequate in 91% of all harvests. The mean DI was 82% (standard deviation, 14%) of the intended DI, which was greater than historic data without PBSC support. Seventeen patients (74%) achieved a complete response (CR), 12 patients with chemotherapy alone and 5 more patients after undergoing surgical resection. Fifteen patients developed progressive disease, with a 2-year event free survival (EFS) rate of 39% (95% confidence interval, 19-59%). Hematopoietic toxicity was severe and cumulative, although it was less than that seen previously without PBSC support. CONCLUSIONS: PBSC-supported multicycle chemotherapy is a feasible method to increase chemotherapy DI for pediatric patients with metastatic sarcomas. Although the CR rate compared favorably with previously reported response rates, the 2-year EFS rate was similar to that achieved with other intensive regimens.

Adolescent↗