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Michael A Thomas

Publications and source records attributed to Michael A Thomas.

18 recordsLinked to original sources
PubMed2006

Model use in phylogenetics: nine key questions.

Models of character evolution underpin all phylogeny estimations, thus model adequacy remains a crucial issue for phylogenetics and its many applications. Although progress has been made in selecting appropriate models for phylogeny estimation, there is still concern about their purpose and proper use. How do we interpret models in a phylogenetic context? What are their effects on phylogeny estimation? How can we improve confidence in the models that we choose? That the phylogenetics community is asking such questions denotes an important stage in the use of explicit models. Here, we examine these and other common questions and draw conclusions about how the community is using and choosing models, and where this process will take us next.

Animals↗
PubMed2006

The monosaccharide transporter gene family in land plants is ancient and shows differential subfamily expression and expansion across lineages.

BACKGROUND: In plants, tandem, segmental and whole-genome duplications are prevalent, resulting in large numbers of duplicate loci. Recent studies suggest that duplicate genes diverge predominantly through the partitioning of expression and that breadth of gene expression is related to the rate of gene duplication and protein sequence evolution.Here, we utilize expressed sequence tag (EST) data to study gene duplication and expression patterns in the monosaccharide transporter (MST) gene family across the land plants. In Arabidopsis, there are 53 MST genes that form seven distinct subfamilies. We created profile hidden Markov models of each subfamily and searched EST databases representing diverse land plant lineages to address the following questions: 1) Are homologs of each Arabidopsis subfamily present in the earliest land plants? 2) Do expression patterns among subfamilies and individual genes within subfamilies differ across lineages? 3) Has gene duplication within each lineage resulted in lineage-specific expansion patterns? We also looked for correlations between relative EST database representation in Arabidopsis and similarity to orthologs in early lineages. RESULTS: Homologs of all seven MST subfamilies were present in land plants at least 400 million years ago. Subfamily expression levels vary across lineages with greater relative expression of the STP, ERD6-like, INT and PLT subfamilies in the vascular plants. In the large EST databases of the moss, gymnosperm, monocot and eudicot lineages, EST contig construction reveals that MST subfamilies have experienced lineage-specific expansions. Large subfamily expansions appear to be due to multiple gene duplications arising from single ancestral genes. In Arabidopsis, one or a few genes within most subfamilies have much higher EST database representation than others. Most highly represented (broadly expressed) genes in Arabidopsis have best match orthologs in early divergent lineages. CONCLUSION: The seven subfamilies of the Arabidopsis MST gene family are ancient in land plants and show differential subfamily expression and lineage-specific subfamily expansions. Patterns of gene expression in Arabidopsis and correlation of highly represented genes with best match homologs in early lineages suggests that broadly expressed genes are often highly conserved, and that most genes have more limited expression.

Arabidopsis↗
PubMed2006

Trizygotic quintuplet pregnancy following simultaneous embryo splitting in an oocyte donatin cycle.

PURPOSE: To report a trizygotic quintuplet pregnancy following simultaneous embryo splitting in an oocyte donation cycle after transfer of 3 embryos. METHODS: A 40-year-old Caucasian female G3P1 with two previous spontaneous abortions and diminished ovarian reserve presented for IVF. The patient underwent an oocyte donation cycle secondary to diminished ovarian reserve. Three embryos were transferred per patient request. RESULTS: The three embryo transfer resulted in a trizygotic quintuplet pregnancy. Selective embryo reduction was performed at 11 weeks leaving a dizygotic twin gestation. The patient underwent SVD, or spontaneous vaginal delivery at 36 weeks gestation with respective weights and apgars of 2673 g (apgars 7(1), 9(5)) and 2722 g (apgars 7(1), 9(5)). The twins are presently doing well without complications. CONCLUSIONS: Although rare, the possibility of simultaneous embryo splitting must be factored into determining number of embryos for fresh transfer.

Adult↗
PubMed2006

Embryo morphology score on day 3 is predictive of implantation and live birth rates.

PURPOSE: To determine if embryo cleavage state or morphology on day 3 correlates with implantation or live birth rates. A retrospective cohort study of all fresh embryo transfers over 2 years. METHODS: Patients were grouped by the average cleavage state and morphology. Cleavage state groups were: <6, > or =6, <8, and > or =8 cells. Morphology groups by average grade were: group 1 (best) = 1, group 2 = >1< or =2, group 3 = >2< or =3, and group 4 (worst) = >3< or =4. RESULTS: The overall implantation rate for 158 cycles was 28.1% with a live birth rate of 37.3%. Morphologic state was highly predictive of both implantation rate and live birth rate. Implantation rates by group were 54.8% (group 1), 30.4% (group 2), 23.8% (group 3), and 11.1% (group 4). Likewise, live birth rates among groups were 61.5, 39, 20, and 21%, respectively. Cleavage state was not predictive of outcome. CONCLUSIONS: Embryo grade is highly predictive of implantation and live birth rate and can be used to determine the number of embryos to transfer. Cleavage state is not predictive of outcome.

Adult↗
PubMed2006

Successful use of vaginal sildenafil citrate in two infertility patients with Asherman's syndrome.

Vaginal sildenafil citrate (Viagra, Pfizer, Inc., New York, NY) has been shown to be useful in increasing endometrial thickness and achieving pregnancy in women with varied uterine disorders. However, it failed to demonstrate favorable results in the setting of Asherman's syndrome, a condition characterized by the presence of uterine synechiae. We have successfully applied this treatment in two women noted to have inadequate endometrium after surgical resection of uterine synechiae. Both patients had a history of a postpartum uterine curettage with subsequent secondary infertility. Asherman's syndrome was surgically demonstrated and treated in both patients. Postoperatively, both patients were noted to have a thin endometrium and failed to conceive despite fertility treatment. Subsequently, these women achieved pregnancy in the first treatment cycle with vaginal sildenafil citrate. Using transvaginal ultrasound, endometrial thickness was noted to improve when sildenafil citrate was administered. It is suspected that this medication causes selective vasodilatation, resulting in improved endometrial development.

Administration, Intravaginal↗
PubMed2005

The effect of multiple cycles in oocyte donors.

OBJECTIVE: The purpose of this study was to determine whether multiple controlled ovarian hyperstimulation cycles in oocyte donors affect the ovarian response, the oocytes retrieved, or the pregnancy rates. STUDY DESIGN: A retrospective chart review of repeat donor in vitro fertilization cycles between 1992 and 2003 at the University of Cincinnati Center for Reproductive Health was performed. The variables that were examined included the peak estradiol level, the length of stimulation, the number of follicles >15 mm, the amount of gonadotropins that were used, the number of oocytes that were retrieved and inseminated, the average number of cells per embryo at the time of transfer, and the clinical pregnancy rates. RESULTS: A total of 107 in vitro fertilized donor oocyte cycles were analyzed, of which 45 young healthy women underwent at least 2 cycles and 17 women underwent 3 cycles. Donors who underwent a second or third cycle demonstrated no differences in the cycle parameters that were observed. CONCLUSION: Repeated controlled ovarian hyperstimulation cycles in a donor population does not demonstrate a diminished ovarian response to exogenous gonadotropins. Oocyte donors can undergo up to 3 stimulation cycles without a negative affect on the ovarian response to gonadotropins, the number of mature oocytes retrieved, the embryo quality, or the clinical pregnancy rate.

Adult↗
PubMed2005

Stabilization and regression of a recurrent desmoid tumor with the antiestrogen toremifene.

OBJECTIVE: To report a case of a pelvic desmoid tumor that was treated with the antiestrogen toremifene after a failed attempt at surgical excision. DESIGN: Case report. SETTING: University reproductive endocrine practice. PATIENT(S): A reproductive-aged woman with a recurrent desmoid tumor. INTERVENTION(S): After surgical excision of a desmoid tumor that presented during childbirth, subsequent recurrence resulted in the use of toremifene for tumor stabilization. MAIN OUTCOME MEASURE(S): Magnetic resonance imaging was used to monitor desmoid tumor size. RESULT(S): One year after postsurgical recurrence of the desmoid tumor, the patient began treatment with the antiestrogen toremifene. Tumor stabilization and regression with symptomatic relief was observed. Nine years of antiestrogen use revealed no progression in tumor size or patient symptoms. After the patient demonstrated perimenopausal symptoms, toremifene administration was discontinued without a return of symptoms or tumor growth after 3 years. CONCLUSION(S): Our case demonstrates that toremifene is a safe and effective therapy that can be used for the stabilization and regression of desmoid tumors. An antiestrogen should be considered as adjuvant therapy after surgery and as a first-line treatment with disease recurrence. Discontinuation of antiestrogen therapy was shown to be done safely after the patient started to show signs of decreased endogenous estrogen production.

Adult↗
PubMed2005

A comparison of three downregulation approaches for poor responders undergoing in vitro fertilization.

OBJECTIVE: To assess the efficacy of three different GnRH agonist (GnRH-a) stimulation regimens to improve ovarian response in poor responders undergoing IVF. DESIGN: Retrospective cohort study. SETTING: Center for Reproductive Health at the University of Cincinnati Medical Center. PATIENT(S): Women diagnosed as poor responders who presented consecutively from January 1999 to January 2004. INTERVENTION(S): Patients underwent three different stimulation regimens during IVF cycles: [1] stop protocol: GnRH-a 500 microg/d administered from the midluteal phase to the start of menses, then gonadotropins from day 2 of cycle, [2] microdose flare: GnRH-a 20 microg administered twice daily with gonadotropins from day 2 to the day of hCG administration, or [3] regular dose flare: gonadotropins beginning with GnRH-a on day 2 at 1 mg/d for 3 days, followed by 250 microg/d until the day of hCG administration. MAIN OUTCOME MEASURE(S): Ovarian response, implantation rates, clinical pregnancy and delivery rates. RESULT(S): Sixty-one IVF cycles were included in the study. None of the comparisons reached statistical significance; however, the microdose group demonstrated a trend toward a higher completed pregnancy rate. CONCLUSION(S): The microdose flare protocol for poor responders demonstrated a trend toward higher delivery rates. A larger prospective study would need to be performed to determine whether this trend leads to a significant finding in this patient population.

Adult↗
PubMed2005

Association of leptin with poor ovarian stimulation during in vitro fertilization.

OBJECTIVE: To evaluate whether serum leptin levels are predictive of in vitrofertilization (IVF) outcome. STUDY DESIGN: A nested, case-control study was performed on patients undergo-formed on patients undergoing IVF. Ovarian stimulation was performed with a set protocol. At the conclusion of the stimulation, patients were divided into 2 groups, poor stimulator (PS) and high stimulator (HS), based on the number of follicles seen on ultrasound. The PS group contained patients with < 12 follicles > 13 mm in diameter; the HS group contained patients with > or = 12 follicles > 13 mm. Blood from the start of the cycle in which human chorionic gonadotropin (hCG) was administered was assayed for leptin and estradiol. The number of follicles obtained, number of oocytes retrieved, quality of the oocytes and quality of the embryos were calculated. Mean leptin and estradiol levels were compared using Student's t test. Pearson correlation coefficients were calculated to assess the relationship between leptin and the other outcome variables. RESULTS: Mean leptin levels (+/- SEM) at the start of the cycle (21.5 +/- 2.9 ng/dL for PS and 34.6 +/- 14.0 ng/dL for HS) and on the day of hCG (53.2 +/- 5.37 ng/dL for PS and 50.4 +/- 9.1 ng/dL for HS) were not significantly different. CONCLUSION: Leptin levels obtained at the start of stimulation or on the day of hCG administration are not predictive of IVF outcome.

Adult↗
PubMed2004

Integrative annotation of 21,037 human genes validated by full-length cDNA clones.

The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.

Alternative Splicing↗
PubMed2004

Genomics for the ecological toolbox.

Genomics technologies have expanded the types of question that can be addressed in human genetics and health and in fields such as ecology. Genome-scale approaches provide ways to examine physiological changes that occur when a pathogen invades a host, the response of an organism to a change in its environment, and the way in which changes in the microbial community affect ecosystem function. Here, we examine successful applications of genomics to ecological science to date and describe ways that classic ecological research disciplines might benefit from genomic approaches. We also address some of the challenges of using this methodology, and discuss how ecological researchers embracing these approaches enhance its effectiveness in applications such as gene hunting and gene expression analysis.

Journal Article↗
PubMed2004

Comparative recombination rates in the rat, mouse, and human genomes.

Levels of recombination vary among species, among chromosomes within species, and among regions within chromosomes in mammals. This heterogeneity may affect levels of diversity, efficiency of selection, and genome composition, as well as have practical consequences for the genetic mapping of traits. We compared the genetic maps to the genome sequence assemblies of rat, mouse, and human to estimate local recombination rates across these genomes. Humans have greater overall levels of recombination, as well as greater variance. In rat and mouse, the size of the chromosome and proximity to telomere have less effect on local recombination rate than in human. At the chromosome level, rat and mouse X chromosomes have the lowest recombination rates, whereas human chromosome X does not show the same pattern. In all species, local recombination rate is significantly correlated with several sequence variables, including GC%, CpG density, repetitive elements, and the neutral mutation rate, with some pronounced differences between species. Recombination rate in one species is not strongly correlated with the rate in another, when comparing homologous syntenic blocks of the genome. This comparative approach provides additional insight into the causes and consequences of genomic heterogeneity in recombination.

Animals↗
PubMed2004

Successful surrogate pregnancy after ovarian transposition, pelvic irradiation and hysterectomy.

BACKGROUND: Treatment of cervical cancer is often effective but at the cost of the woman's fertility. Ovarian transposition with subsequent oocyte retrieval and surrogate pregnancy can enable these patients to become genetic parents. We present the third reported such case. CASE: A 22-year-old woman was diagnosed with bulky, stage IB cervical cancer. Following transposition of both ovaries to the upper abdomen, she underwent pelvic irradiation followed by total abdominal hysterectomy. Eleven years later she presented for assisted reproduction. Two oocytes were retrieved following ovarian stimulation and transcutaneous, abdominal oocyte retrieval. One embryo was transferred to the gestational surrogate, resulting in a single intrauterine pregnancy and successful delivery at term. CONCLUSION: These procedures can preservefertility while successfully treating cervical cancer.

Embryo Transfer↗
PubMed2004

Timing of hCG administration does not affect pregnancy rates in couples undergoing intrauterine insemination using clomiphene citrate.

BACKGROUND: Therapeutic intrauterine insemination (IUI) combined with clomiphene citrate ovarian stimulation is widely used to improve pregnancy rates for a variety of disorders. The goal of this study was to elucidate whether hCG administration at 24 or 36 hours after clomiphene citrate stimulation impacts pregnancy rates. METHODS: The study was conducted as a retrospective chart review of 182 clomiphene citrate/IUI cycles in 90 women at the Center for Reproductive Health at the University of Cincinnati Medical Center. Comparisons were made between IUls performed at 24 hours versus 36 hours after hCG. Clinical variables included age of the female partner, semen concentration and motility, and infertility diagnosis. Outcomes were pregnancy rates and live birth rates. Data analysis was performed using Chi square for proportions and Student's t-test for continuous variables. RESULTS: The pregnancy rate was 7% in the 24-hour group and 15.9% in the 36-hour group (P=0.057). However, the live birth rate was 4.0% in the 24-hour group and 8.5% in the 36-hour group (P=0.2). CONCLUSIONS: There is no significant difference in pregnancy rates in couples utilizing clomiphene citrate and undergoing IUI, whether hCG is administered at 24 hours or 36 hours prior to the procedure.

Adult↗
PubMed2003

Evolutionary dynamics of oncogenes and tumor suppressor genes: higher intensities of purifying selection than other genes.

Oncogenes and tumor suppressor genes (hereafter referred to as "cancer genes") result in cancer when they experience substitutions that prevent or distort their normal function. We examined evolutionary pressures acting on cancer genes and other classes of disease-related genes and compared our results to analyses of genes without known association to disease. We compared synonymous and nonsynonymous substitution rates in 3,035 human genes-approximately 10% of the genome-measuring the intensity of purifying selection on 311 human disease genes, including 122 cancer-related genes. Although the genes examined are similar to nondisease genes in product, expression, function, and pathway affiliation, we found intriguing differences in the selective pressures experienced by cancer genes relative to other (noncancer) disease-related and non-disease-related genes. We found a statistically significant increase in the intensity of purifying selection exerted on cancer genes (the average ratio of nonsynonymous to synonymous substitutions, omega, was 0.079) relative to all other disease-related genes groups (omega = 0.101) and non-disease-related genes (omega = 0.100). This difference indicates a striking increase in selection against nonsynonymous substitutions in oncogenes and tumor suppressor genes. This finding provides insight into the etiology of cancer and the differences between genes involved in cancer and those implicated in other human diseases. Specifically, we found a significant overlap between human oncogenes and tumor suppressor genes and "essential genes," human homologs of mouse lethal genes identified by knockout experiments. This insight may improve our ability to identify cancer-related genes and enhances our understanding of the nature of these genes.

Evolution, Molecular↗
PubMedDate not supplied

The motility of epididymal or testicular spermatozoa does not directly affect IVF/ICSI pregnancy outcomes.

Our objective was to determine whether the presence of motility in surgically obtained sperm samples improves fertilization and pregnancy rates for patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). This was a retrospective study in a hospital-based infertility center. Sixty-seven couples with a diagnosis of azoospermia or severe oligozoospermia who had undergone a sperm retrieval procedure in conjunction with 100 IVF/ICSI cycles from 1995 to 2004 were evaluated. The impact of sperm motility on fertilization and clinical pregnancy rates was determined. The motile and nonmotile sperm groups differed in the number of mature oocytes retrieved (10.7 +/- 5.8 vs 13.4 +/- 6.0), but fertilization (56.7% vs 59.1%) and embryo cryopreservation rates (35.9% vs 39.3%) were statistically similar. Clinical pregnancy rates did not differ between the motile (38.5%) and nonmotile (31.2%) groups, nor did they differ between obstructive and nonobstructive patients (35.3% vs 26.7%). There was also no statistical difference in pregnancy rates between testicular and epididymal aspiration (35.3% vs 26.7%), although epididymal sperm were significantly more likely to be motile than testicular sperm (100% vs 39.3%, P < .0001). Epididymal aspiration is more likely to produce motile sperm than testicular sperm retrieval. The use of motile sperm from epididymal or testicular samples, however, does not appear to enhance fertilization or clinical pregnancy rates.

Adult↗