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Biomedical subjects

B Elliott

Publications and source records attributed to B Elliott.

At least 19 recordsLinked to original sources
PubMed2002

Double-strand breaks and translocations in cancer.

The correct repair of double-strand breaks (DSBs) is essential for the genomic integrity of a cell, as inappropriate repair can lead to chromosomal rearrangements such as translocations. In many hematologic cancers and sarcomas, translocations are the etiological factor in tumorigenesis, resulting in either the deregulation of a proto-oncogene or the expression of a fusion protein with transforming properties. Mammalian cells are able to repair DSBs by pathways involving homologous recombination and nonhomologous end-joining. The analysis of translocation breakpoints in a number of cancers and the development of model translocation systems are beginning to shed light on specific DSB repair pathway(s) responsible for the improper repair of broken chromosomes.

Burkitt Lymphoma↗
PubMed2001

Co-operative effect of c-Src tyrosine kinase and Stat3 in activation of hepatocyte growth factor expression in mammary carcinoma cells.

We have previously shown coexpression of hepatocyte growth factor (HGF) and its receptor Met in the invasive tumor front of human breast carcinomas. We have also demonstrated secretion of HGF, constitutive activation of Met, and increased invasion in a murine breast carcinoma cell line, SP1. These observations suggest the presence of an HGF autocrine loop in some breast carcinoma cells, which confers increased survival, growth, and invasiveness during tumor progression and metastasis. c-Src tyrosine kinase, which is critical in regulating the expression of many genes, is activated in SP1 carcinoma cells, as well as in most human breast cancers. We therefore examined the role of c-Src kinase in HGF expression in breast carcinoma cells. Expression of activated c-Src in SP1 cells increased transcription from the HGF promoter and expression of HGF mRNA and protein, while dominant negative c-Src had the opposite effect. Using deletion analysis, we showed that the region between -254 and -70 base pairs was required for c-Src responsiveness of the HGF promoter. This region contains two putative consensus sequences (at -110 and -149 base pairs) for the Stat3 transcription factor, which bind protein complexes containing Stat3 (but not Stat1, -5A, or -5B). Coexpression of activated c-Src and Stat3 synergistically induced strong HGF promoter activity in SP1 cells, as well as in a nonmalignant epithelial cell line, HC11 (HGF negative). c-Src kinase activity correspondingly increased the tyrosine 705 phosphorylation and DNA binding affinity of Stat3 (but not Stat1, -5A, or -5B). Collectively, our data indicate a cooperative effect of c-Src kinase and Stat3 in the activation of HGF transcription and protein expression in breast carcinoma cells. This process may be important in overriding the strong repression of HGF expression in nonmalignant epithelium, and thereby promote tumorigenesis.

Animals↗
PubMed2001

Repair of double-strand breaks by homologous recombination in mismatch repair-defective mammalian cells.

Chromosomal double-strand breaks (DSBs) stimulate homologous recombination by several orders of magnitude in mammalian cells, including murine embryonic stem (ES) cells, but the efficiency of recombination decreases as the heterology between the repair substrates increases (B. Elliott, C. Richardson, J. Winderbaum, J. A. Nickoloff, and M. Jasin, Mol. Cell. Biol. 18:93-101, 1998). We have now examined homologous recombination in mismatch repair (MMR)-defective ES cells to investigate both the frequency of recombination and the outcome of events. Using cells with a targeted mutation in the msh2 gene, we found that the barrier to recombination between diverged substrates is relaxed for both gene targeting and intrachromosomal recombination. Thus, substrates with 1.5% divergence are 10-fold more likely to undergo DSB-promoted recombination in Msh2(-/-) cells than in wild-type cells. Although mutant cells can repair DSBs efficiently, examination of gene conversion tracts in recombinants demonstrates that they cannot efficiently correct mismatched heteroduplex DNA (hDNA) that is formed adjacent to the DSB. As a result, >20-fold more of the recombinants derived from mutant cells have uncorrected tracts compared with recombinants from wild-type cells. The results indicate that gene conversion repair of DSBs in mammalian cells frequently involves mismatch correction of hDNA rather than double-strand gap formation. In cells with MMR defects, therefore, aberrant recombinational repair may be an additional mechanism that contributes to genomic instability and possibly tumorigenesis.

Animals↗
PubMed2001

The Health Insurance Portability and Accountability Act (HIPAA) and physician compliance.

The Administration and Simplification Provisions and the Standards for Privacy of Individually Identifiable Health Information Section of HIPAA (Health Insurance Portability and Accountability Act) will have a significant impact on the daily operations of most physicians' practices. The HIPAA legislation is summarized, and these two sections of HIPAA are discussed in detail. The rationale for the regulations, their substance and intent, and physician compliance strategies are discussed.

Delaware↗
PubMed2001

Bioterrorism, physician education, and the Internet.

To meet the challenges of bioterrorism, the practicing physician must have information that is authoritative, specific, and timely with respect to any outbreaks or suspected outbreaks of bioterrorism. Educational activities for physicians and other health care workers are important. In the United States, bioterrorism was not an issue until October 2001, and bioterrorism disease organisms are not ones commonly dealt with in civilian health care. Web sites that satisfy these information and educational requirements are discussed.

Bioterrorism↗
PubMed2000

High volume medical web sites.

In 1998, 22 million individuals reported surfing the web for medical information, and this number will increase to over 30 million by 2000. Fifteen of the highest volume medical web sites are described in this paper. Sponsorship and/or ownership of the fifteen sites varied. The government sponsors one, and some are the products of well-known educational institutions. One site is supported by a consumer health organization, and the American Medical Association was in the top 15. However, the most common owners are commercial, for-profit businesses. Attributes of the ideal site were categorized, and include a robust privacy and disclosure statement with an emphasis on education and an appropriate role for advertising. The covering of Complementary and Alternative Medicine (CAM) should be in a balanced and unbiased manner. There has to be an emphasis on knowledge based evidence as opposed to testimonials, and sources should be timely and reviewed. Bibliographies of authors need to be available. Hyperlinking to other web resources is valuable, as even the largest of sites cannot come close to covering all of medicine.

Confidentiality↗
PubMed2000

Cooperative effect of hepatocyte growth factor and fibronectin in anchorage-independent survival of mammary carcinoma cells: requirement for phosphatidylinositol 3-kinase activity.

Anchorage-independent survival and growth are critical characteristics of malignant cells. We showed previously that the addition of exogenous hepatocyte growth factor (HGF) and the presence of fibronectin fibrils stimulate anchorage-independent colony growth of a murine mammary carcinoma, SP1, which expresses both HGF and HGF receptor (Met; R. Saulnier et al., Exp. Cell Res., 222: 360-369, 1996). We now show that tyrosine phosphorylation of Met in carcinoma cells is augmented by cell adhesion and spreading on fibronectin substratum. In contrast, detached serum-starved cells exhibit reduced tyrosine phosphorylation of Met and undergo apoptotic cell death within 18-24 h. Under these conditions, the addition of HGF stimulates tyrosine phosphorylation of Met and restores survival of carcinoma cells. Soluble fibronectin also stimulates cell survival and shows a cooperative survival response with HGF but does not affect tyrosine phosphorylation of Met; these results indicate that fibronectin acts via a pathway independent of Met in detached cells. We demonstrated previously that inhibition of phosphatidylinositol (PI) 3-kinase activity blocks HGF-induced DNA synthesis of carcinoma cells (N. Rahimi et al., J. Biol. Chem., 271: 24850-24855, 1996). We now show in detached cells a cooperative effect of HGF and FN in the activation of PI 3-kinase and on the phosphorylation of PKB/Akt at serine 473. PI 3-kinase activity is also required for the HGF- and fibronectin-induced survival responses, as well as anchorage-independent colony growth. However, c-Src kinase or MEK1/2 activities are not required for the cell survival effect. Together, these results demonstrate that the PI 3-kinase/Akt pathway is a key effector of the HGF- and fibronectin-induced survival response of breast carcinoma cells under detached conditions and corroborate an interaction between integrin and HGF/ Met signalling pathways in the development of invasive breast cancer.

Animals↗
PubMed2000

Diagnosing and treating hypothyroidism.

Hypothyroidism is a common endocrine disorder affecting 1.4% to 2.0% of women and 0.1% to 0.2% of men. The prevalence of both overt and subclinical hypothyroidism increases with age, affecting 5% to 10% of women over age 50 and 1.25% of men over age 60, with an increasing incidence in women ages 40 to 50. Typical symptoms are consistent with declining metabolic functions and range from vague complaints of fatigue in subclinical deficiency to overt clinical symptoms involving changes in mentation and memory, lethargy, weight gain, cold intolerance, constipation, and goitrous enlargement of the thyroid gland. Atypical presentations such as weight loss, hearing impairment, tinnitus, and carpal tunnel syndrome may occur, especially in the elderly. This case report reviews the presenting symptomatology of an otherwise healthy 43-year-old woman who exhibited typical and atypical symptoms of underlying thyroid deficiency.

Adult↗
PubMed2000

Creating a physician web site: Part One.

The reasons why physicians should have professional web sites for their practices are presented. The options available to practitioners who want to create a site are reviewed. Advantages and disadvantages of virtual and non-virtual hosting are discussed. How to find and register one's own domain name, obtain a hosting service, and avenues available to build the web site are also described. Future articles will address finding specific hosting services and details regarding site construction.

Humans↗
PubMed2000

Creating a physician Web site: Part 2.

An individual physician web site is a valuable augmentation to a professional practice. Enhancing patient care and increasing customer satisfaction are the most important goals of a physician web venue. Broadening your patient base, improving practice efficiencies, helping ensure corporate compliance, and decreasing liability exposure can also be accomplished by a well thought out and constructed site. Pages presenting information about the practice, the delineation of patient responsibilities, and evidence-based clinical content information will constitute the majority of the site. A user agreement and disclaimer page, feedback page, and corporate compliance page constitute the supplementary pages on the site.

Delaware↗
PubMed1999

Ready, steady?

Explore the source record for details and available documents.

Financing, Government↗
PubMed1999

Biomechanics: an integral part of sport science and sport medicine.

Biomechanics is one of the disciplines in the field of Human Movement and Exercise Science and it can be divided into three broad categories from a research perspective. Clinical biomechanics involves research in the areas of gait, neuromuscular control, tissue mechanics, and movement evaluation during rehabilitation from either injury or disease. Occupational biomechanics typically involves research in the areas of ergonomics and human growth or morphology as they influence movement. While these two categories will briefly be discussed, the primary aim of this paper is to show the role of biomechanics in sports science and sports medicine. Research in sports biomechanics may take the form of describing movement from a performance enhancement (such as matching of impulse curves in rowing) or injury reduction perspective (such as diving in swimming or the assessment of knee joint loading during downhill walking). However, the strength of sports biomechanics research is the ability to establish an understanding of causal mechanisms for selected movements (such as the role of internal rotation of the upper arm in hitting or striking, and the influence of elastic energy and muscle pre-stretch in stretch-shorten-cycle actions). The growth of modelling and computer simulation has further enhanced the potential use of sports biomechanics research (such as quantification of knee joint ligament forces from a dynamic model and optimising gymnastics performance through simulation of in-flight movements). Biomechanics research may also play an integral role in reducing the incidence and severity of sporting injuries (such as identification of the causes of back injuries in cricket, and the causes of knee joint injuries in sport). In the following discussion no attempt will be made to reference all papers published in each of these areas because of the enormity of the task. Published and current work from the biomechanics laboratory at the Department of Human Movement and Exercise Science at The University of Western Australia will generally be used to illustrate the scope of biomechanics research within that institution.

Athletic Injuries↗
PubMed1999

Medical text books on the World Wide Web.

The availability of medical textbooks for physicians on the web is rapidly increasing. Internet sites that maintain a listing of such resources are briefly described, and descriptions of particularly valuable fee based and free medical textbooks web sites are categorized.

Internet↗
PubMed1998

c-Src kinase activity is required for hepatocyte growth factor-induced motility and anchorage-independent growth of mammary carcinoma cells.

Overexpression and amplification of hepatocyte growth factor (HGF) receptor (Met) have been detected in many types of human cancers, suggesting a critical role for Met in growth and development of malignant cells. However, the molecular mechanism by which Met contributes to tumorigenesis is not well known. The tyrosine kinase c-Src has been implicated as a modulator of cell proliferation, spreading, and migration; these functions are also regulated by Met. To explore whether c-Src kinase is involved in HGF-induced cell growth, a mouse mammary carcinoma cell line (SP1) that co-expresses HGF and Met and a nonmalignant epithelial cell line (Mv1Lu) that expresses Met but not HGF were used. In this study, we have shown that c-Src kinase activity is constitutively elevated in SP1 cells and is induced in response to HGF in Mv1Lu cells. In addition, c-Src kinase associates with Met following stimulation with HGF. The enhanced activity of c-Src kinase also correlates with its ability to associate with Met. Expression of a dominant negative double mutant of c-Src (SRC-RF), lacking both kinase activity (K295R) and a regulatory tyrosine residue (Y527F), in SP1 cells significantly reduced c-Src kinase activity and strongly blocked HGF-induced motility and colony growth in soft agar. In contrast, expression of the dominant negative c-Src mutant had no effect on HGF-induced cell proliferation on plastic. Taken together, our data strongly suggest that HGF-induced association of c-Src with Met and c-Src activation play a critical role in HGF-induced cell motility and anchorage-independent growth of mammary carcinomas and further support the notion that the presence of paracrine and autocrine HGF loops contributes significantly to the transformed phenotype of carcinoma cells.

Animals↗
PubMed1998

Autocrine secretion of TGF-beta 1 and TGF-beta 2 by pre-adipocytes and adipocytes: a potent negative regulator of adipocyte differentiation and proliferation of mammary carcinoma cells.

We have developed an in vitro system to examine the influence of adipocytes, a major mammary stromal cell type, on the growth of a murine mammary carcinoma, SP1. Previously, we have shown that 3T3-L1 adipocytes release a mitogenic factor, hepatocyte growth factor, which strongly stimulates proliferation of SP1 cells. We now show that 3T3-L1 pre-adipocytes secrete active inhibitory molecules which inhibit DNA synthesis in SP1 cells. In addition, latent inhibitory activity is present in conditioned media (CM) from both pre-adipocytes and adipocytes, and is activated following acid treatment. CM also inhibited DNA synthesis in Mv1Lu wild type epithelial cells, but not DR27 mutant epithelial cells which lack TGF-beta type II receptor. Inhibitory activity of CMs was partially abrogated by neutralizing anti-TGF-beta1 and anti-TGF-beta2 antibodies, and was removed following ultrafiltration through membranes of 10,000 Mr but not 30,000 Mr pore size. These results show that the inhibitory effect on DNA synthesis is mediated by TGF-beta1-like and TGF-beta2-like molecules. In addition, acid-treated CM as well as purified TGF-beta inhibited differentiation of pre-adipocytes. Untreated pre-adipocyte CM, but not mature adipocyte CM, spontaneously inhibited adipocyte differentiation. Together, these findings indicate that pre-adipocytes spontaneously activate their own secreted TGF-beta, whereas mature adipocytes do not, and suggest that activation of TGF-beta has a potent negative regulatory effect on adipocyte differentiation and tumor growth. Thus, TGF-beta may be an important modulator of tumor growth and adipocyte differentiation via both paracrine and autocrine mechanisms. These findings emphasize the importance of adipocyte-tumor interactions in the regulation of tumor microenvironment.

3T3 Cells↗