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Full-Text Articles in Medicine and Health Sciences
Like Father, Like Son, Katrina Bramstedt
Like Father, Like Son, Katrina Bramstedt
Katrina A. Bramstedt
This is a review of the Japanese film, Like Father, Like Son. The movie tells the story of two families attempting to resolve the dilemma of learning that their 6-year old sons are actually not their biological children, but rather children swapped at birth by a nurse with malicious intent.
A Mouse Model For Beta 0-Thalassemia., Baoli Yang, S. Kirby, J. Lewis, P. Detloff, N. Maeda, O. Smithies
A Mouse Model For Beta 0-Thalassemia., Baoli Yang, S. Kirby, J. Lewis, P. Detloff, N. Maeda, O. Smithies
Baoli Yang
We have used a "plug and socket" targeting technique to generate a mouse model of beta 0-thalassemia in which both the b1 and b2 adult globin genes have been deleted. Mice homozygous for this deletion (Hbbth-3/Hbbth-3) die perinatally, similar to the most severe form of Cooley anemia in humans. Mice heterozygous for the deletion appear normal, but their hematologic indices show characteristics typical of severe thalassemia, including dramatically decreased hematocrit, hemoglobin, red blood cell counts, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration, as well as dramatically increased reticulocyte counts, serum bilirubin concentrations, and red cell distribution …
Appropriate Tissue- And Cell-Specific Expression Of A Single Copy Human Angiotensinogen Transgene Specifically Targeted Upstream Of The Hprt Locus By Homologous Recombination., B. Cvetkovic, Baoli Yang, R. Williamson, C. Sigmund
Appropriate Tissue- And Cell-Specific Expression Of A Single Copy Human Angiotensinogen Transgene Specifically Targeted Upstream Of The Hprt Locus By Homologous Recombination., B. Cvetkovic, Baoli Yang, R. Williamson, C. Sigmund
Baoli Yang
Development of experimental models by genetic manipulation in mice has proven to be very useful in determining the significance of particular genes in the development of or susceptibility to hypertension. Advances in molecular genetics, transgenic mouse technology, and physiological measurements in mice provided an opportunity to go a step further and develop models to analyze the physiological significance of specific gene variants potentially causing hypertension. In this report, we describe the development of a human angiotensinogen transgenic mouse model generated by targeting the human angiotensinogen gene upstream of the mouse HPRT locus by homologous recombination. The main benefit of this …
Identification Of A Tripartite Basal Promoter Which Regulates Human Terminal Deoxynucleotidyl Transferase Gene Expression., D. Bhaumik, Baoli Yang, T. Trangas, J. Bartlett, M. Coleman, D. Sorscher
Identification Of A Tripartite Basal Promoter Which Regulates Human Terminal Deoxynucleotidyl Transferase Gene Expression., D. Bhaumik, Baoli Yang, T. Trangas, J. Bartlett, M. Coleman, D. Sorscher
Baoli Yang
In order to locate the promoter region of the human terminal deoxynucleotidyl transferase gene, serially truncated segments of the 5'-flanking region of the gene were cloned into a chloramphenicol acetyltransferase reporter vector. Transient transfection analyses of the terminal transferase-reporter gene constructs identified the basal promoter region within -34 to +40 base pairs relative to the transcription start site. Three promoter elements were defined in this region. The primary element is within 34 base pairs upstream of the transcription start site. The CAP site is 62 base pairs upstream of the translation start site. The secondary element involves sequences around the …
Regulation Of Terminal Deoxynucleotidyl Transferase Gene Expression In Mice And Men., M. Coleman, Baoli Yang, D. Sorscher
Regulation Of Terminal Deoxynucleotidyl Transferase Gene Expression In Mice And Men., M. Coleman, Baoli Yang, D. Sorscher
Baoli Yang
A nontemplate directed DNA polymerase, terminal deoxynucleotidyl transferase (terminal transferase) is expressed in a tissue-specific and development stage-specific manner. Its enzymatic properties and tissue localization have implicated the protein in development of normal immune function. Significant progress has been made in understanding the enzymology and important domains of this protein. More recently, studies have focused on regulation of the gene that codes for the protein in mice and humans. The murine gene has yielded to these studies more readily than the human gene. A murine basal promoter element has been identified along with several trans-acting protein factors that may regulate …
Mutational Analysis Of Residues In The Nucleotide Binding Domain Of Human Terminal Deoxynucleotidyl Transferase., Baoli Yang, K. Gathy, M. Coleman
Mutational Analysis Of Residues In The Nucleotide Binding Domain Of Human Terminal Deoxynucleotidyl Transferase., Baoli Yang, K. Gathy, M. Coleman
Baoli Yang
Human terminal deoxynucleotidyl transferase (TdT) was overexpressed in a baculovirus system. The pure recombinant enzyme was identical in size, activity, kinetic constants, and metal effects to native enzyme. Three amino acids, within either the putative nucleotide binding domain and part of a DNA polymerase consensus sequence, YGDTDSLF, or a TdT consensus sequence, GGFRRGK, were altered by site-directed mutagenesis. The four mutant forms of terminal transferase were also overexpressed in the baculovirus expression system and purified from Trichoplusia ni larvae by a monoclonal antibody affinity column and compared with wild-type enzyme with respect to thermostabilities, secondary structure, metal effects, and kinetic …
Pharmacogenetic Screening For Susceptibility To Fetal Malformations In Women, D. Van Dyke, V. Ellingrod, M. Berg, Jennifer Niebyl, A. Sherbondy, D. Trembath
Pharmacogenetic Screening For Susceptibility To Fetal Malformations In Women, D. Van Dyke, V. Ellingrod, M. Berg, Jennifer Niebyl, A. Sherbondy, D. Trembath
Jennifer R Niebyl
OBJECTIVE: To present a review of the literature and research on the pharmacogenetics of congenital defects, with a focus on the need for predictive maternal genotype assays. DATA SOURCE: MEDLINE searches (January 1985-January 1999), past reference reviews, and unpublished research. STUDY SELECTION: Review of relevant human, animal, and basic science studies. DATA EXTRACTION: Data on research on polymorphisms, genotyping, cytochrome P450 enzyme systems, epoxide hydrolase, folate metabolism, metabolism of anticonvulsant medications, molecular genetics of neural tube defects, variations in drug metabolism, and environmental exposures were evaluated. DATA SYNTHESIS: Data synthesis includes not only a review of the literature but suggests …
Progesterone Regulation Of Activating Protein-1 Transcriptional Activity: A Possible Mechanism Of Progesterone Inhibition Of Endometrial Cancer Cell Growth, Donghai Dai, E. S. Litman, E. Schonteich, K. K. Leslie
Progesterone Regulation Of Activating Protein-1 Transcriptional Activity: A Possible Mechanism Of Progesterone Inhibition Of Endometrial Cancer Cell Growth, Donghai Dai, E. S. Litman, E. Schonteich, K. K. Leslie
Donghai Dai
The uterine endometrium and cancers derived from it are classic models of hormone action: estrogen promotes growth and progesterone inhibits proliferation and results in differentiation. We have now identified a major pathway through which progesterone causes these growth-limiting effects. Ligand-bound progesterone receptors modulate the composition and transcriptional activity of members of the activating protein-1 (AP-1) family, and in particular, c-Jun. First, a dominant negative form of c-Jun inhibits the constitutive growth of Hec50co cells in a manner similar to the effects of progesterone through progesterone B receptors. Second, progesterone inhibits the transcriptional activity of the AP-1 complex in reporter gene …
Quantitative Interpretation Of A Genetic Model Of Carcinogenesis Using Computer Simulations, Donghai Dai, B. Beck, X. Wang, C. Howk, Y. Li
Quantitative Interpretation Of A Genetic Model Of Carcinogenesis Using Computer Simulations, Donghai Dai, B. Beck, X. Wang, C. Howk, Y. Li
Donghai Dai
The genetic model of tumorigenesis by Vogelstein et al. (V theory) and the molecular definition of cancer hallmarks by Hanahan and Weinberg (W theory) represent two of the most comprehensive and systemic understandings of cancer. Here, we develop a mathematical model that quantitatively interprets these seminal cancer theories, starting from a set of equations describing the short life cycle of an individual cell in uterine epithelium during tissue regeneration. The process of malignant transformation of an individual cell is followed and the tissue (or tumor) is described as a composite of individual cells in order to quantitatively account for intra-tumor …
Selective Down-Regulation Of Progesterone Receptor Isoform B In Poorly Differentiated Human Endometrial Cancer Cells: Implications For Unopposed Estrogen Action., N. Kumar, J. Richer, G. Owen, E. Litman, K. Horwitz, Kimberly Leslie
Selective Down-Regulation Of Progesterone Receptor Isoform B In Poorly Differentiated Human Endometrial Cancer Cells: Implications For Unopposed Estrogen Action., N. Kumar, J. Richer, G. Owen, E. Litman, K. Horwitz, Kimberly Leslie
Kimberly K. Leslie
The uterine endometrium responds to unopposed estrogen stimulation with rapid cell proliferation. Progesterone protects the endometrium against the hyperplastic effects of estradiol (E2) through progesterone receptors (PRs), of which two isoforms are expressed: human (h) PRA and PRB. hPRB has a longer NH2 terminus and may function differently from hPRA. Thus, the relative expression of hPRA:hPRB is likely to be important for the action of progesterone. We hypothesized that the hPRA:hPRB ratios may be abnormal in endometrial cancer, leading to a lack of normal progesterone protection against the growth-promoting effects of E2. To test this hypothesis, well-differentiated Ishikawa endometrial cancer …
Estrogen Receptors Are Present In Human Granulosa Cells., B. Hurst, M. Zilberstein, J. Chou, B. Litman, J. Stephens, Kimberly Leslie
Estrogen Receptors Are Present In Human Granulosa Cells., B. Hurst, M. Zilberstein, J. Chou, B. Litman, J. Stephens, Kimberly Leslie
Kimberly K. Leslie
Recent studies failed to detect estrogen receptors in primate follicles. This study was initiated to determine whether estrogen receptor (ER) messenger ribonucleic acid (mRNA) is present in human granulosa cells and, further, if functional ER proteins are present. To evaluate the presence of ER, RNA from human granulosa cells obtained at the time of oocyte retrieval for assisted reproduction was extracted, and complementary DNA synthesis was performed by the reverse transcriptase-polymerase chain reaction. Oligonucleotide primers were used to amplify basepairs 570-852 in the B- and C- domains of the ER mRNA. Southern blotting was performed and confirmed that the amplified …
The Role Of Oestrogen In Follicular Development., B. Hurst, Kimberly Leslie
The Role Of Oestrogen In Follicular Development., B. Hurst, Kimberly Leslie
Kimberly K. Leslie
Most of our knowledge of ovarian physiology is based upon studies that have demonstrated functional oestrogen receptors in the ovaries of lower animal species. The presence of oestrogen receptors in primate granulosa cells has been questioned by some investigators. However, we have found oestrogen receptor messenger RNA in human granulosa cells by reverse transcriptase-PCR assay. Furthermore, using immortalized granulosa cell lines transfected with a plasmid containing an oestrogen response element, a functional oestrogen receptor was confirmed. These experiments strongly support the hypothesis that human granulosa cells express biologically active oestrogen receptor.
Estrogen Receptors Are Identified In The Glioblastoma Cell Line U138mg., Kimberly Leslie, D. Keefe, S. Powell, F. Naftolin
Estrogen Receptors Are Identified In The Glioblastoma Cell Line U138mg., Kimberly Leslie, D. Keefe, S. Powell, F. Naftolin
Kimberly K. Leslie
OBJECTIVE: The antiestrogen tamoxifen has been found to be effective in decreasing glioblastoma cell proliferation, but the mechanism underlying this effect and whether it is through the estrogen receptor (ER) is controversial. The objective of this study was to determine whether ERs are present in three human glioblastoma cell lines--HS683, U138MG, and JHN J889H--using the most sensitive techniques available. METHODS: Ligand binding and flow cytometry were employed to identify estrogen and progesterone receptors. The reverse transcriptase-polymerase chain reaction was used to identify ER mRNA, and a novel reporter gene transfection assay demonstrated that the ER was capable of activating gene …
A Phase Ii Evaluation Of Lapatinib In The Treatment Of Persistent Or Recurrent Epithelial Ovarian Or Primary Peritoneal Carcinoma: A Gynecologic Oncology Group Study, A. Garcia, M. Sill, H. Lankes, A. Godwin, R. Mannel, D. Armstrong, R. Carolla, M. Liepman, N. Spirtos, E. Fischer, Kimberly Leslie
A Phase Ii Evaluation Of Lapatinib In The Treatment Of Persistent Or Recurrent Epithelial Ovarian Or Primary Peritoneal Carcinoma: A Gynecologic Oncology Group Study, A. Garcia, M. Sill, H. Lankes, A. Godwin, R. Mannel, D. Armstrong, R. Carolla, M. Liepman, N. Spirtos, E. Fischer, Kimberly Leslie
Kimberly K. Leslie
OBJECTIVE: Activation and dimerization of the ERBB family play a role in the pathogenesis and progression of ovarian cancer. We conducted a phase II trial to evaluate the activity and tolerability of lapatinib in patients with recurrent or persistent epithelial ovarian cancer (EOC) and to explore the clinical value of expression levels of epidermal growth factor receptors (EGFR), phosphorylated EGFR, HER-2/neu, and Ki-67, and the presence of EGFR mutations. METHODS: Eligible patients had recurrent or persistent EOC or primary peritoneal carcinoma, measurable disease, and up to 2 prior chemotherapy regimens for recurrent disease. Patients were treated with lapatinib 1500 mg/day. …
Progesterone Regulation Of Activating Protein-1 Transcriptional Activity: A Possible Mechanism Of Progesterone Inhibition Of Endometrial Cancer Cell Growth, Donghai Dai, E. Litman, E. Schonteich, Kimberly Leslie
Progesterone Regulation Of Activating Protein-1 Transcriptional Activity: A Possible Mechanism Of Progesterone Inhibition Of Endometrial Cancer Cell Growth, Donghai Dai, E. Litman, E. Schonteich, Kimberly Leslie
Kimberly K. Leslie
The uterine endometrium and cancers derived from it are classic models of hormone action: estrogen promotes growth and progesterone inhibits proliferation and results in differentiation. We have now identified a major pathway through which progesterone causes these growth-limiting effects. Ligand-bound progesterone receptors modulate the composition and transcriptional activity of members of the activating protein-1 (AP-1) family, and in particular, c-Jun. First, a dominant negative form of c-Jun inhibits the constitutive growth of Hec50co cells in a manner similar to the effects of progesterone through progesterone B receptors. Second, progesterone inhibits the transcriptional activity of the AP-1 complex in reporter gene …
Microdeletions At Chromosome Bands 1q32-Q41 As A Cause Of Van Der Woude Syndrome, B. Schutte, A. Basart, Y. Watanabe, J. Laffin, K. Coppage, B. Bjork, Sandra Daack-Hirsch, S. Patil, M. Dixon, J. Murray
Microdeletions At Chromosome Bands 1q32-Q41 As A Cause Of Van Der Woude Syndrome, B. Schutte, A. Basart, Y. Watanabe, J. Laffin, K. Coppage, B. Bjork, Sandra Daack-Hirsch, S. Patil, M. Dixon, J. Murray
Sandra Daack-Hirsch
Van der Woude syndrome (VWS) is an autosomal dominant disorder comprising cleft lip and/or cleft palate and lip pits. We reported previously a family whose underlying mutation is a 500-800 kb deletion localized to chromosome bands 1q32-q41 [Sander et al., 1994: Hum Mol Genet 3:576-578]. Along with cleft lip/palate and lip pits, affected relatives exhibit developmental delays, suggesting that the function of a gene nearby may also be disrupted. To further localize the VWS gene we searched for other deletions that cause VWS. An allele loss assay was performed using a novel highly polymorphic marker, D1S3753. From a panel of …
Discordant Mz Twins With Cleft Lip And Palate: A Model For Identifying Genes In Complex Traits, M. Mansilla, J. Kimani, L. Mitchell, K. Christensen, D. Boomsma, Sandra Daack-Hirsch, B. Nepomucena, D. Wyszynski, T. Felix, N. Martin, J. Murray
Discordant Mz Twins With Cleft Lip And Palate: A Model For Identifying Genes In Complex Traits, M. Mansilla, J. Kimani, L. Mitchell, K. Christensen, D. Boomsma, Sandra Daack-Hirsch, B. Nepomucena, D. Wyszynski, T. Felix, N. Martin, J. Murray
Sandra Daack-Hirsch
Monozygotic (MZ) twins may be discordant for complex traits due to differential environmental exposure in utero, epigenetic variability in imprinting, X chromosome inactivation, or stochastic effects. Occasionally MZ twins may be discordant for chromosomal and single gene disorders due to somatic mosaicism. For complex traits, which are due to the interactive effects of multiple genes and environmental factors, the affected twin of a discordant MZ pair offers the possibility for identifying somatic mutations in candidate genes. DNA sequencing of candidate genes in discordant MZ twins can identify those rare etiologic mutational events responsible for the different phenotypes since the confounding …
X-Chromosome Inactivation Patterns In Monozygotic Twins And Sib Pairs Discordant For Nonsyndromic Cleft Lip And/Or Palate, J. Kimani, M. Shi, Sandra Daack-Hirsch, K. Christensen, D. Moretti-Ferreira, M. Marazita, L. Field, J. Canady, J. Murray
X-Chromosome Inactivation Patterns In Monozygotic Twins And Sib Pairs Discordant For Nonsyndromic Cleft Lip And/Or Palate, J. Kimani, M. Shi, Sandra Daack-Hirsch, K. Christensen, D. Moretti-Ferreira, M. Marazita, L. Field, J. Canady, J. Murray
Sandra Daack-Hirsch
Nonsyndromic clefts of the lip and/or palate are common birth defects with a strong genetic component. Based on unequal gender ratios for clefting phenotypes, evidence for linkage to the X chromosome and the occurrence of several X-linked clefting syndromes, we investigated the role of skewed X chromosome inactivation (XCI) in orofacial clefts. Our samples consisted of female monozygotic (MZ) twins (n = 8) and sister pairs (n = 152) discordant for nonsyndromic clefting. We measured the XCI pattern in peripheral blood lymphocyte DNA using a methylation based androgen receptor gene assay. Skewing of XCI was defined as the deviation in …
Interferon Regulatory Factor 6 (Irf6) Gene Variants And The Risk Of Isolated Cleft Lip Or Palate, T. Zucchero, M. Cooper, B. Maher, Sandra Daack-Hirsch, B. Nepomuceno, L. Ribeiro, D. Caprau, K. Christensen, Y. Suzuki, J. Machida, N. Natsume, K. Yoshiura, A. Vieira, I. Orioli, E. Castilla, L. Moreno, M. Arcos-Burgos, A. Lidral, L. Field, Y. Liu, A. Ray, T. Goldstein, R. Schultz, M. Shi, M. Johnson, S. Kondo, B. Schutte, M. Marazita, J. Murray
Interferon Regulatory Factor 6 (Irf6) Gene Variants And The Risk Of Isolated Cleft Lip Or Palate, T. Zucchero, M. Cooper, B. Maher, Sandra Daack-Hirsch, B. Nepomuceno, L. Ribeiro, D. Caprau, K. Christensen, Y. Suzuki, J. Machida, N. Natsume, K. Yoshiura, A. Vieira, I. Orioli, E. Castilla, L. Moreno, M. Arcos-Burgos, A. Lidral, L. Field, Y. Liu, A. Ray, T. Goldstein, R. Schultz, M. Shi, M. Johnson, S. Kondo, B. Schutte, M. Marazita, J. Murray
Sandra Daack-Hirsch
BACKGROUND: Cleft lip or palate (or the two in combination) is a common birth defect that results from a mixture of genetic and environmental factors. We searched for a specific genetic factor contributing to this complex trait by examining large numbers of affected patients and families and evaluating a specific candidate gene. METHODS: We identified the gene that encodes interferon regulatory factor 6 (IRF6) as a candidate gene on the basis of its involvement in an autosomal dominant form of cleft lip and palate, Van der Woude's syndrome. A single-nucleotide polymorphism in this gene results in either a valine or …