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Biomedical subjects

E A Stewart

Publications and source records attributed to E A Stewart.

At least 19 recordsLinked to original sources
PubMed2001

A high-resolution radiation hybrid map of the human genome draft sequence.

We have constructed a physical map of the human genome by using a panel of 90 whole-genome radiation hybrids (the TNG panel) in conjunction with 40,322 sequence-tagged sites (STSs) derived from random genomic sequences as well as expressed sequences. Of 36,678 STSs on the TNG radiation hybrid map, only 3604 (9.8%) were absent from the unassembled draft sequence of the human genome. Of 20,030 STSs ordered on the TNG map as well as the assembled human genome draft sequence and the Celera assembled human genome sequence, 36% of the STSs had a discrepant order between the working draft sequence and the Celera sequence. The TNG map order was identical to one of the two sequence orders in 60% of these discrepant cases.

Algorithms↗
PubMed2001

Uterine fibroids.

Uterine leiomyomas (fibroids or myomas), benign tumours of the human uterus, are the single most common indication for hysterectomy. They are clinically apparent in up to 25% of women and cause significant morbidity, including prolonged or heavy menstrual bleeding, pelvic pressure or pain, and, in rare cases, reproductive dysfunction. Thus, both the economic cost and the effect on quality of life are substantial. Surgery has been the mainstay of fibroid treatment, and various minimally invasive procedures have been developed in addition to hysterectomy and abdominal myomectomy. Formation of new leiomyomas after these conservative therapies remains a substantial problem. Although medications that manipulate concentrations of steroid hormones are effective, side-effects limit long-term use. A better approach may be manipulation of the steroid-hormone environment with specific hormone antagonists. There has been little evidence-based evaluation of therapy. New research into the basic biology of these neoplasms may add new treatment options for the future as the role of growth factors and genetic mutations in these tumours are better understood.

Abdominal Pain↗
PubMed2000

Transcervical placement of a Malecot catheter after hysteroscopic evaluation provides for easier entry into the endometrial cavity for women with histories of difficult intrauterine inseminations and/or embryo transfers: a prospective case series.

OBJECTIVE: To evaluate a new technique designed to improve access to the endometrial cavity through tortuous and/or stenotic endocervical canals in women with histories of difficult IUIs, ETs, or endometrial biopsies. DESIGN: Prospective case series. SETTING: Tertiary care center. PATIENT(S): Women with histories of difficult intrauterine procedures because of tortuous and/or stenotic endocervical canals who continued to undergo treatment. INTERVENTION(S): Hysteroscopic evaluation and/or correction of the endocervix, followed by transcervical placement of a Malecot catheter (CR Bard Inc., Covington, GA) for an average of 10 days. MAIN OUTCOME MEASURE(S): Improvement in the ease of access to the endometrial cavity during IUIs or ETs. RESULT(S): Thirty-two of 36 patients had significantly easier procedures after the placement and removal of a Malecot catheter. CONCLUSION(S): Hysteroscopic evaluation and placement of a Malecot catheter is a useful technique that allows easier entry through the cervical canal in patients in whom previous IUIs, ETs, and endometrial biopsies have been difficult. This procedure may lead to improved pregnancy rates, particularly with IVF-ET, as the ease of ET has been correlated with improved implantation rates.

Adult↗
PubMed2000

Towards the social analysis of twinship.

The article examines the proposition that twinship is an irreducibly social phenomenon. Gender, age, birth order, socio-economic status and other variables are considered, along with the role of different patterns of socialization as these affect twinship. It is argued that, to a very large extent, from conception. through gestation, childbirth and subsequently childhood and adolescence, the social processing and regulation of social members take place in unitary terms and that therefore twins (and higher multiples) are an anomaly in relation to such processes. Twins' reactions to stigma, stereotyping and labelling are explored as an integral aspect of the social structuring of twinship. The role of the twin, as distinct from the role of the non-twin, is examined in the context of cultural expectations of twinship regarding similarity of identity and similarity of behaviour. Subsequent or concurrent processes of differentiation between twins are also examined. The article concludes with suggestions for further analyses of twinship.

Adolescent↗
PubMed2000

The comparative constitution of twinship: strategies and paradoxes.

In both traditional and modern societies, twinship, as an unusual mode of reproduction, involves difficulties for social systems in maintaining consistent classification systems. It is proposed that the most prevalent response to twinship involves various 'strategies of normalisation' to defuse and contain the potential disruption. This proposition is illustrated and analysed in relation to ethnographic maternal drawn mainly (but not exclusively) from African communities in the twentieth century. Following a discussion of twin infanticide as the most extreme of the normalising strategies, the article concludes by identifying a number of paradoxes in the social construction of twinship.

Africa↗
PubMed1999

Messenger ribonucleic acid for the gonadal luteinizing hormone/human chorionic gonadotropin receptor is not present in human endometrium.

OBJECTIVE: To determine whether messenger RNA for the gonadal LH/hCG receptor is present in human endometrium with the use of reverse-transcriptase polymerase chain reaction. DESIGN: In vitro experiment. SETTING: Academic medical center. PATIENT(S): Premenopausal women who were not receiving hormonally active medications and who were undergoing hysterectomy for uterine leiomyomas, menorrhagia, pelvic pain, or uterine prolapse. INTERVENTION(S): Tissue from hysterectomy specimens was processed for RNA and treated with deoxyribonuclease where appropriate, and RNA was reverse-transcribed to complementary DNA. MAIN OUTCOME MEASURE(S): An appropriately sized band after reverse-transcriptase polymerase chain reaction, followed by sequencing to confirm the results. RESULT(S): A primer pair that spanned the extracellular domain was unable to amplify receptor complementary DNA from human endometrial tissue. For a primer pair that spanned transmembrane regions 2-6 of the receptor and was contained wholly in exon 11, a 552-base pair fragment was amplified successfully in 19 of 25 human endometrial samples. CONCLUSION(S): The traditional gonadal LH/hCG receptor does not appear to be present in human endometrial tissue. The presence of a portion of the transmembrane part of the molecule suggests that human endometrium may express a truncated or variant form of the receptor.

Adult↗
PubMed1999

Onapristone suppresses prolactin production in explant cultures of leiomyoma.

OBJECTIVE: To assess the action of onapristone, a type I antiprogestin, on prolactin (PRL) production by explant cultures of leiomyoma and myometrium. DESIGN: Explant cultures of myometrium and leiomyomas from 3 premenopausal women undergoing hysterectomy in the proliferative phase of the menstrual cycle. MAIN OUTCOME MEASURES: PRL secretion measured by radioimmunoassay. RESULTS: PRL secretion was decreased in leiomyomas by onapristone. There was no effect in the myometrium. There was no additional effect with the addition of the type II antiprogestin mifepristone (RU 486). CONCLUSION: PRL production is suppressed in leiomyomas but not in myometrium after treatment with onapristone in vitro. This suppression may serve as a marker for the clinical effectiveness of agents used in the treatment of leiomyomas.

Culture Techniques↗
PubMed1999

Prolactin is an autocrine or paracrine growth factor for human myometrial and leiomyoma cells.

OBJECTIVE: To test the hypothesis that prolactin (PRL) acts as a mitogenic growth factor for human leiomyoma and myometrial cells. METHODS: To test this hypothesis, we performed three different types of experiments. First, we assessed whether exogenous PRL acted as a mitogen for cultured uterine smooth muscle cells. Second, we examined the role of endogenous PRL by assessing the cell number after exposure of the cultures to a neutralizing antibody to PRL. Finally, we examined both fresh tissues and cultured cells for expression of the PRL receptor messenger ribonucleic acid using the techniques of reverse-transcriptase polymerase chain reaction and Southern blotting. RESULTS: A significant suppression in cell number was seen after 5 days of culture for leiomyoma cells but not for myometrial cells after treatment with exogenous PRL. Both cell types showed a significant decrease in cell number after treatment with anti-PRL antibody. A 893-bp segment consistent with the cytoplasmic domain of the long form of the PRL receptor was amplified from both fresh and cultured tissues and confirmed by Southern blotting and sequencing. CONCLUSIONS: PRL appears to be an autocrine or paracrine growth factor for both leiomyoma and myometrial cells. However, there are some differences between tissues in their sensitivity to this growth factor.

Antibodies↗
PubMed1998

A physical map of 30,000 human genes.

A map of 30,181 human gene-based markers was assembled and integrated with the current genetic map by radiation hybrid mapping. The new gene map contains nearly twice as many genes as the previous release, includes most genes that encode proteins of known function, and is twofold to threefold more accurate than the previous version. A redesigned, more informative and functional World Wide Web site (www.ncbi.nlm.nih.gov/genemap) provides the mapping information and associated data and annotations. This resource constitutes an important infrastructure and tool for the study of complex genetic traits, the positional cloning of disease genes, the cross-referencing of mammalian genomes, and validated human transcribed sequences for large-scale studies of gene expression.

Animals↗
PubMed1998

New concepts in the treatment of uterine leiomyomas.

Uterine leiomyomas are a common clinical occurrence for gynecologists. The current approach to treating these neoplasms is shaped by classic surgical principles and the knowledge that these tumors are responsive to the gonadal steroids estrogen and progesterone. As knowledge of leiomyomas advances through the techniques of molecular biology and molecular genetics, new concepts are developed that go beyond just myomas as steroid-responsive tumors. Understanding the molecular events involved in the transformation of a normal myometrial cell into a neoplastic cell and the subsequent growth of these leiomyoma cells will be important in determining the pathogenesis of these tumors and providing new targets for treatment. Knowing the role of peptide growth factors, including basic fibroblast growth factor and transforming growth factor-beta, in the pathogenesis of leiomyoma-related symptoms might lead to new treatments targeting these molecules or their receptors. As the effects of genes, including HMGIC and HMGI(Y), are determined; new treatments to prevent leiomyoma formation or growth may be developed. As we gain understanding of the molecular events that cause benign gynecologic conditions such as leiomyomas, safer and more effective treatments might be found as we enter the 21st century.

Female↗
PubMed1998

Interferon-alpha is a potent inhibitor of basic fibroblast growth factor-stimulated cell proliferation in human uterine cells.

PROBLEM: Abnormal uterine bleeding is a significant health problem for many women and is the number-one reason for performing hysterectomy in the United States. Leiomyomas (uterine fibroids) are benign neoplasms that are a frequent cause of abnormal uterine bleeding. The goal of this study was to assess the effects of the anti-angiogenic cytokine, interferon (INF)-alpha, on the proliferation of both leiomyoma and normal uterine cells. METHOD OF STUDY: Primary cultures of leiomyoma, myometrial, and endometrial stromal cells were established for in vitro study. The effects of INF-alpha (10, 100, and 1000 U/ml) were tested on serum-stimulated and basic fibroblast growth factor-stimulated cell proliferation using the [3H]thymidine incorporation assay. RESULTS: INF-alpha was a potent inhibitor of cell proliferation for all three cell types, with endometrial stromal cells showing the greatest sensitivity. The antiproliferative effect did not appear to result from toxic effects on the cells. CONCLUSION: INFs may prove to be useful therapeutic agents for the treatment of leiomyoma-related abnormal uterine bleeding.

Cell Division↗
PubMed1997

Expression of the fibroblast growth factor receptor in women with leiomyomas and abnormal uterine bleeding.

Basic fibroblast growth factor (bFGF) is a regulator of angiogenesis which is overexpressed in leiomyomas compared with matched myometrium. To understand the physiological significance of this finding we characterized the expression of the type 1 receptor for this ligand (FGFR1). Utilizing reverse transcription-polymerase chain reaction (RT-PCR) we identified the complete and alternatively spliced transmembrane forms and two secreted forms of the FGFR1 in endometrium, myometrium and leiomyomas from all patients. This is the first report of secreted forms in uterine tissue. Proteins consistent with each of these isoforms were identified by Western blot analysis in all three tissues. Immunohistochemistry revealed menstrual cycle-specific regulation of FGFR1 protein in the endometrial stroma of normal women but not in women with leiomyomas and abnormal uterine bleeding. Stromal FGFR1 expression is suppressed in the early luteal phase in normal women, but not in women with leiomyoma-related bleeding. These findings support the role of the bFGF ligand-receptor system in the pathogenesis of leiomyoma-related bleeding and may have implications for fertility and contraception since the differential FGFR1 expression occurs in the peri-implantation period of the early luteal phase.

Adult↗
PubMed1997

An STS-based radiation hybrid map of the human genome.

We have constructed a physical map of the human genome by using a panel of 83 whole genome radiation hybrids (the Stanford G3 panel) in conjunction with 10,478 sequence-tagged sites (STSs) derived from random genomic DNA sequences, previously mapped genetic markers, and expressed sequences. Of these STSs, 5049 are framework markers that fall into 1766 high-confidence bins. An additional 945 STSs are indistinguishable in their map location from one or more of the framework markers. These 5994 mapped STSs have an average spacing of 500 kb. An additional 4484 STSs are positioned with respect to the framework markers. Comparison of the orders of markers on this map with orders derived from independent meiotic and YAC STS-content maps indicates that the error rate in defining high-confidence bins is < 5%. Analysis of 322 random cDNAs indicates that the map covers the vast majority of the human genome. This STS-based radiation hybrid map of the human genome brings us one step closer to the goal of a physical map containing 30,000 unique ordered landmarks with an average marker spacing of 100 kb.

Animals↗
PubMed1996

A gene map of the human genome.

The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.

Amino Acid Sequence↗
PubMed1996

Transthoracic needle biopsy with a coaxially placed 20-gauge automated cutting needle: results in 122 patients.

PURPOSE: To determine the utility of coaxial transthoracic needle biopsy (TNB) with use of a 20-gauge automated cutting biopsy needle in the diagnosis of thoracic lesions. MATERIALS AND METHODS: A retrospective review was performed in 122 patients. Computed tomography was used to guide coaxial TNB, which was performed with aspirating (n = 87) and automated cutting (n = 99) needles. The sensitivities for malignant and benign lesions were determined, with a comparison of the relative yields from the two techniques. RESULTS: The overall diagnostic yield for coaxial TNB was 88%. For malignancy the sensitivity was 95%, whereas a specific benign diagnosis was obtained in 91%. Although no difference was found for fine-needle aspiration versus core biopsy of malignant lesions (92% vs 86%), a statistically significant difference was found for benign lesions (44% vs 100%, P<.05). Pneumothorax occurred in 54%. CONCLUSION: Coaxial TNB performed with an automated cutting needle helps provide a diagnosis in the majority of patients with focal chest disease and is particularly useful in the diagnosis of benign lesions.

Adolescent↗
PubMed1996

RU486 suppresses prolactin production in explant cultures of leiomyoma and myometrium.

OBJECTIVE: To assess the action of RU486 (mifepristone), in the presence and absence of P, on PRL production by explant cultures of leiomyoma and myometrium. DESIGN: Explant cultures using tissue from nine premenopausal women undergoing hysterectomy in the proliferative phase of the menstrual cycle; immunohistochemical staining of tissue sections from five patients for P receptor (PR) subtype. MAIN OUTCOME MEASURES: Prolactin secretion (measured by RIA), lactate dehydrogenase secretion (measured by quantitative colorimetric assay), and immunohistochemistry for PR subtype. RESULTS: Prolactin secretion was decreased in leiomyomas by RU486 at concentrations of 10(-7) M and 10(-5)M when normal serum-containing medium was used. In experiments with all detectable P removed from serum, PRL secretion was suppressed in both leiomyomas and myometrium at an RU486 concentration of 10(-7)M. Immunohistochemistry results suggest that the A form of the PR is the dominant form in both leiomyomas and myometrium. CONCLUSIONS: Prolactin production is suppressed in both leiomyomas and myometrium after treatment with RU486 in vitro, and this suppression may serve as a marker for the clinical effectiveness of agents used in the treatment of leiomyomas.

Culture Media↗