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Biomedical subjects

Judy Anderson

Publications and source records attributed to Judy Anderson.

13 recordsLinked to original sources
PubMed2006

Normalizing the bone marrow microenvironment with p38 inhibitor reduces multiple myeloma cell proliferation and adhesion and suppresses osteoclast formation.

The multiple myeloma (MM) bone marrow (BM) microenvironment plays a critical role in supporting tumor growth and survival as well as in promoting formation of osteolytic lesions. Recent results suggest that the p38 mitogen-activated protein kinase (MAPK) is an important factor in maintaining this activated environment. In this report, we demonstrate that the p38alpha MAPK inhibitor, SCIO-469, suppresses secretion of the tumor-supportive factors IL-6 and VEGF from BM stromal cells (BMSCs) as well as cocultures of BMSCs with MM cells, resulting in reduction in MM cell proliferation. Additionally, we show that SCIO-469 prevents TNFalpha-induced adhesion of MM cells to BMSCs through an ICAM-1- and VCAM-1-independent mechanism. Microarray analysis revealed a novel set of TNFalpha-induced chemokines in BMSCs that is strongly inhibited by SCIO-469. Furthermore, reintroduction of chemokines CXCL10 and CCL8 to BMSCs overcomes the inhibitory effect of SCIO-469 on TNFalpha-induced MM adhesion. Lastly, we show that SCIO-469 inhibits secretion and expression of the osteoclast-activating factors IL-11, RANKL, and MIP-1alpha as well as prevents human osteoclast formation in vitro. Collectively, these results suggest that SCIO-469 treatment can suppress factors in the bone marrow microenvironment to inhibit MM cell proliferation and adhesion and also to alleviate osteolytic activation in MM.

Animals↗
PubMed2006

Alpha9beta1: a novel osteoclast integrin that regulates osteoclast formation and function.

UNLABELLED: We identified a previously unknown integrin, alpha(9)beta(1), on OCLs and their precursors. Antibody to alpha(9) inhibited OCL formation in human marrow cultures, and OCLs from alpha(9) knockout mice had a defect in actin ring reorganization and an impaired bone resorption capacity. INTRODUCTION: Integrins play important roles in osteoclast (OCL) formation and function. Mature OCLs mainly express alpha(v)beta(3) integrin, a heterodimer adhesion receptor that has been implicated in osteoclastic bone resorption. We identified ADAM8, a disintegrin and metalloproteinase, as a novel stimulator of OCL differentiation and showed that the disintegrin domain of ADAM8 mediated its effects on OCL formation. Because the disintegrin domain of ADAM8 does not bind Arg-Gly-Asp (RGD) sequences, we determined which integrin bound ADAM8 and characterized its role in OCL formation and activity. MATERIALS AND METHODS: Chinese hamster ovary cells (CHO) expressing different integrin subunits were tested for their capacity to bind the disintegrin domain of ADAM8. Mouse or human bone marrow cells and purified OCL precursors were tested for alpha(9)beta(1) integrin expression by Western blot, immunocytochemistry, and real-time RT-PCR. A monoclonal antibody to human alpha(9) was used to block alpha(9)beta(1) on OCL precursors stimulated by 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] or RANKL. Vertebrae of 7-day-old alpha(9)(-/-) mice and wildtype (WT) littermates were compared using bone histomorphometry and 3D microCT analysis. RESULTS: Alpha(9) integrin was expressed by mouse and human bone marrow-derived OCLs and their precursors. Importantly, the anti-alpha(9) antibody inhibited human OCL formation stimulated by 1alpha,25(OH)(2)D(3) or RANKL dose-dependently. Furthermore, analysis of OCLs formed in marrow cultures from alpha(9)(-/-) mice showed that the OCLs formed were more contracted and formed significantly less bone resorption pits on dentin slices. Histologic analysis of alpha(9)(-/-) vertebrae showed thickened trabecular regions and retained cartilage within vertebral bodies of alpha(9)(-/-) mice. 3D microCT analysis of alpha(9)(-/-) vertebrae also showed a significant increase in trabecular bone volume/total tissue volume and a tendency for decreased trabecular separation compared with WT mice. CONCLUSIONS: These results support a previously unknown role for alpha(9)beta(1) integrin in OCL formation and function.

ADAM Proteins↗
PubMed2005

Thalidomide derivative CC-4047 inhibits osteoclast formation by down-regulation of PU.1.

CC-4047, an immunomodulatory analog of thalidomide, inhibits multiple myeloma with unknown effects on the human osteoclast lineage. Early osteoclast progenitors are of hematopoietic origin and differentiate into mature bone resorbing multinucleated osteoclasts. We investigated the effects of CC-4047 and thalidomide on human osteoclastogenesis, using in vitro receptor activator of NFkappa-B ligand/macrophage colony-stimulating factor-stimulated bone marrow cell cultures. Treating bone marrow cultures with CC-4047 for 3 weeks decreased osteoclast formation accompanied by complete inhibition of bone resorption. The inhibitory effect was similar when cultures were treated for 3 weeks or for only the first week (90% inhibition), indicating that CC-4047 inhibits early stages of osteoclast formation. Inhibition of osteoclastogenesis by CC-4047 was mediated by a shift of lineage commitment to granulocyte colony-forming units at the expense of granulocyte-macrophage colony-forming units. Further studies revealed that this shift in lineage commitment was mediated through down-regulation of PU.1. Treatment with thalidomide resulted in significantly less potent inhibition of osteoclast formation and bone resorption. These results provide evidence that CC-4047 blocks osteoclast differentiation during early phases of osteoclastogenesis. Therefore, CC-4047 might be a valuable drug for targeting both tumors and osteoclastic activity in patients with multiple myeloma and other diseases associated with osteolytic lesions.

Angiogenesis Inhibitors↗
PubMed2005

Utilization of different aquaporin water channels in the mouse cervix during pregnancy and parturition and in models of preterm and delayed cervical ripening.

Biochemical changes of cervical connective tissue, including progressive disorganization of the collagen network and increased water content, occur during gestation to allow for cervical dilatation during labor, but the mechanisms that regulate cervical fluid balance are not fully understood. We examined whether aquaporins (AQPs), a family of membrane channel proteins that facilitate water transport, help mediate fluid balance in the mouse cervix during parturition. Of the 13 known murine AQPs, AQP0-2, 6, 7, 9, 11, and 12 were absent or at the limits of detection. By Northern blot and real-time PCR, AQP3 expression was low in nongravid and mid-pregnancy cervices with peak expression on d 19 and postpartum d 1 (PP1). AQP4 expression was generally low throughout pregnancy but showed a small upward trend at the time of parturition. AQP5 and AQP8 expression were significantly increased on d 12-15 but fell to nongravid/baseline by d 19 and PP1. By in situ hybridization and immunohistochemistry, AQP3 was preferentially expressed in basal cell layers of the cervical epithelium, whereas AQP4, 5, and 8 were primarily expressed in apical cell layers. Females with LPS-induced preterm labor had similar trends in AQP4, 5, and 8 expression to mice with natural labor at term gestation. Mice with delayed cervical remodeling due to deletion of the steroid 5alpha-reductase type 1 gene showed significant reduction in the levels of AQP3, 4, and 8 on d 19 or PP1. Together, these studies suggest that AQPs 3, 4, 5, and 8 regulate distinct aspects of cervical water balance during pregnancy and parturition.

Animals↗
PubMed2005

Antioxidative function of L-FABP in L-FABP stably transfected Chang liver cells.

Liver fatty acid binding protein (L-FABP) contains amino acids that are known to possess antioxidant function. In this study, we tested the hypothesis that L-FABP may serve as an effective endogenous cytoprotectant against oxidative stress. Chang liver cells were selected as the experimental model because of their undetectable L-FABP mRNA level. Full-length L-FABP cDNA was subcloned into the mammalian expression vector pcDNA3.1 (pcDNA-FABP). Chang cells were stably transfected with pc-DNA-FABP or vector (pcDNA3.1) alone. Oxidative stress was induced by incubating cells with 400 micromol/L H2O2 or by subjecting cells to hypoxia/reoxygenation. Total cellular reactive oxygen species (ROS) was determined using the fluorescent probe DCF. Cellular damage induced by hypoxia/reoxygenation was assayed by lactate dehydrogenase (LDH) release. Expression of L-FABP was documented by regular reverse transcription polymerase chain reaction (RT-PCR), real-time RT-PCR, and Western blot. The pcDNA-FABP-transfected cells expressed full-length L-FABP mRNA, which was absent from vector-transfected control cells. Western blot showed expression of 14-kd L-FABP protein in pcDNA-FABP-transfected cells, but not in vector-transfected cells. Transfected cells showed decreased DCF fluorescence intensity under oxidative stress (H2O2 and hypoxia/reoxygenation) conditions versus control in inverse proportion to the level of L-FABP expression. Lower LDH release was observed in the higher L-FABP-expressed cells in hypoxia/reoxygenation experiments. In conclusion, we successfully transfected and cloned a Chang liver cell line that expressed the L-FABP gene. The L-FABP-expressing cell line had a reduced intracellular ROS level versus control. This finding implies that L-FABP has a significant role in oxidative stress.

Antioxidants↗
PubMed2005

Documentation of preoperative counselling for female sterilisation: a complete audit cycle.

BACKGROUND: Female sterilisation is a commonly performed gynaecological procedure that attracts a disproportionate number of complaints and litigation. Documentation of the key counselling issues provides an important record of the information given to the woman prior to undergoing sterilisation. METHODS: Auditable standards were obtained from published guidelines. After the initial audit of 100 cases a proforma was introduced in an effort to improve documentation. A re-audit of 50 cases was undertaken to ascertain compliance of documentation following the introduction of the proforma. RESULTS: The proforma was used in 62% of cases and in all such cases documentation was 100% compliant with the auditable standards. Overall, documentation of standards pre- and post-proforma, respectively, was as follows (all the figures quoted are percentage values, with the range given in parentheses): 33 (24-43) vs 68 (53-80) for long-term alternatives, 94 (87-98) vs 78 (62-87) for irreversibility, 96 (90-99) vs 78 (64-88) for failure rate, 48 (38-58) vs 66 (51-79) for ectopic pregnancy risk if sterilisation fails, 39 (29-49) vs 66 (51-79) for the intended method, 67 (57-76) vs 66 (51-79) for operative risks and 37 (28-47) vs 64 (49-77) for continuing current contraception until sterilisation performed. CONCLUSIONS: Documentation of preoperative counselling for female sterilisation is often incomplete and does not comply with published recommendations. The introduction of a proforma resulted in a mixture of both improvement and deterioration of documentation. When the proforma was used, compliance with recommendations was 100%.

Counseling↗
PubMed2004

Patency of the preterm fetal ductus arteriosus is regulated by endothelial nitric oxide synthase and is independent of vasa vasorum in the mouse.

Patency of the fetal ductus arteriosus (DA) is maintained in an environment of low relative oxygen tension and a preponderance of vasodilating forces. In addition to prostaglandins, nitric oxide (NO), a potent vasodilator in the pulmonary and systemic vasculatures, has been implicated in regulation of the fetal DA. To further define the contribution of NO to DA patency, the expression and function of NO synthase (NOS) isoforms were examined in the mouse DA on days 17-19 of pregnancy and after birth. Our results show that endothelial NOS (eNOS) is the predominant isoform expressed in the mouse DA and is localized in the DA endothelium by in situ hybridization. Despite rapid constriction of the DA after birth, eNOS expression levels were unchanged throughout the fetal and postnatal period. Pharmacological inhibition of prostaglandin vs. NO synthesis in vivo showed that the preterm fetal DA on day 16 is more sensitive to NOS inhibition than the mature fetal DA on day 19, whereas prostaglandin inhibition results in marked DA constriction on day 19 but minimal effects on the day 16 DA. Combined prostaglandin and NO inhibition caused additional DA constriction on day 16. The contribution of vasa vasorum to DA regulation was also examined. Immunoreactive platelet endothelial cell adhesion molecule and lacZ tagged FLK1 localized to DA endothelial cells but revealed the absence of vasa vasorum within the DA wall. Similarly, there was no evidence of vasa vasorum by vascular casting. These studies indicate that eNOS is the primary source of NO in the mouse DA and that vasomotor tone of the preterm fetal mouse DA is regulated by eNOS-derived NO and is potentiated by prostaglandins. In contrast to other species, mechanisms for DA patency and closure appear to be independent of any contribution of the vasa vasorum.

Animals↗
PubMed2003

Molecular phenotype of spontaneously arising 4N (G2-tetraploid) intermediates of neoplastic progression in Barrett's esophagus.

Elevated 4N (G(2)-tetraploid) cell populations are unstable intermediates in the development of many human cancers. However, 4N cell populations are intermixed with larger diploid fractions in vivo, limiting investigation of these key intermediates of neoplastic progression. Therefore, to study elevated 4N cell populations in human neoplasia, we used flow cytometry to purify populations of spontaneously arising TP53(wt) and TP53(mut) 4N cells from cell strains derived from premalignant Barrett's esophagus biopsies. Using oligonucleotide arrays, we identified 625 genes differentially expressed in at least one replicate 2N/4N comparison in each strain and in hTERT-immortalized cultures of the TP53(mut) strains. Strikingly, when hierarchically clustered, these data contained a large node of 124 genes that were up-regulated in 4N TP53(mut) cells in the absence of condensed chromosomes. Most of these genes function in G(2)-M to mediate processes such as chromosome condensation and segregation. These results describe the molecular phenotype of dysregulated G(2)-M functions and cell cycle checkpoints in a key intermediate of human neoplastic progression.

Barrett Esophagus↗
PubMed2003

Neonatal pemphigus foliaceus.

The term "pemphigus" refers to a group of diseases that are characterized by the presence of cutaneous or mucosal blisters and erosions, and antiepidermal autoantibodies. There are several case reports of neonatal pemphigus vulgaris in the literature. Although pemphigus foliaceus antibodies have been shown to cross the placenta, to our knowledge, this is only the second reported case of neonatal pemphigus foliaceus. The proposed mechanism of disease transfer is the passive transfer of maternal IgG antibodies across the placenta.

Administration, Topical↗
PubMed2002

Activation of muscle satellite cells in single-fiber cultures.

Satellite stem cell activation is the process by which quiescent precursor cells resident on muscle fibers are recruited to cycle and move. Two processes are reported to affect satellite cell activation. In vivo, nitric oxide (NO) produced by NO synthase in fibers (NOS-Imu) promotes activation. In cell cultures, hepatocyte growth factor (HGF) is the major activating factor isolated from crushed muscle extract (CME). In this study we hypothesized that distinct and possibly related events were mediated by NO and HGF during activation. Intact fibers were cultured in the presence of bromodeoxyuridine (BrdU) to label DNA synthesis over 48 h. Experiments were designed to test the effects of CME, HGF, a NOS substrate L-arginine, and the NOS inhibitor L-NAME on activation, determined as the number of BrdU-positive satellite cells per fiber. Activation was increased significantly by CME, HGF, and L-arginine. L-Arginine increased activation in a dose-response manner. CME-induced activation was reduced significantly by NOS inhibition. Exposure to marcaine (10 min) caused reversible membrane damage without hypercontraction, as shown by characterizing the sarcolemmal integrity. The resulting decrease in satellite cell activation could be overcome by exogenous HGF. Results support the hypothesis that NO is involved in recruiting to cycle those satellite cells resident on fibers. Separate assessments of resident and free muscle cells showed that HGF and NO also participate in mobilizing satellite cells. Since HGF counteracted NOS inhibition and marcaine-induced membrane damage, data suggest that NO may mediate early steps in activation and precede HGF-mediated events.

Animals↗
PubMed2002

A study to assess patient satisfaction of transitioning from Medicaid to managed care by sickle cell patients in Hampton Roads, Virginia.

Transition issues faced by the sickle cell patient who has a significant chronic illness or disability are many and often life threatening. The problems that are faced in transitioning from Medicaid to managed care are many that could hinder the process and patient satisfaction. Such problems during the transition periods could stem from interrupted health care services; improperly coordinated services; inappropriate intervention; and inappropriate or unfounded psychologically diagnosed cases (Blum, 1993). It is not known which health care programs are cost-effective and which are not. Nor is it known which health care program best meets the needs of patients with chronic illnesses or varying levels of severity; and it is not known if health status actually improves as a result of transitioning from one program to another. What factors then impact the satisfaction levels in transitioning from Medicaid to managed care for sickle cell patients in Hampton Roads, Virginia? This study looked at patient satisfaction with the transition from Medicaid to managed care as related to the cost of care, quality of care, and access to care.

Adolescent↗
PubMed1993

Lessons Learned and Baseline Data from Initiating Smoking Cessation Research with Southeast Asian Adults.

PURPOSES OF THE PAPER: The purposes of this paper are as follows: (1) discuss seven design considerations and their respective lessons learned or resolutions in initiating the National Institutes of Health's only funded smoking cessation grant targeting Asian Americans; (2) present empirical findings that resulted from the design considerations alluded to previously; and (3) delineate unresolved challenges on conducting smoking cessation research particularly for adult Southeast Asians. SUMMARY OF METHODS UTILIZED: The authors base this paper on their empirical data collected as part of the "Lay-led Smoking Cessation Approach for S.E. Asian men" study. Data collected include baseline data from 1553 adult Southeast Asians (721 women and 832 men) in Ohio as well as subsequent data collected on selected individuals. The investigators faced seven major, conceptual issues in initiating smoking cessation research focusing on Southeast Asian adults. These seven considerations related to: language, culture, nicotine addiction characteristics, verification of smoking exposure and smoking status, knowledge of the health consequences of smoking, social environmental factors, and criteria for evaluating effectiveness of the proposed intervention. Smoking cessation interventions must be conducted in the appropriate Asian language because current smokers are the least likely to understand spoken English. Culturally speaking, Cambodian and Laotian male smokers are significantly more likely to have traditional Southeast Asian values than their never smoker counterparts. As a measure of addiction to nicotine, the median time until the first cigarette was 30 minutes for both Cambodians and Vietnamese suggesting that these men are highly addicted. Cotinine levels were negatively correlated with time to the first cigarette and positively correlated with numbers of cigarettes. Knowledge of the health consequences of smoking is lower than mainstream populations. Almost 100 per cent of Southeast Asian male smokers have at least one "best" friend who smokes. Verification of smoking status through saliva cotinine testing suggest that actual smoking rates among Southeast Asians are higher than self­report rates. The largest proportion of Cambodian and Vietnamese smokers are in the precontemplation stage while Laotian smokers are proportionally more likely to be in the contemplation stage. CONCLUSIONS: Design considerations discussed represent considerations beyond those that are normally considered in community­based research for majority populations. The quality and quantity of empirical data collected with due attention to these conceptual considerations appear to substantiate the validity of these considerations. Authors delineated challenges for initiating smoking cessation research among Southeast Asians. RELEVANCE TO ASIAN PACIFIC ISLANDER AMERICAN POPULATIONS: This paper is particularly relevant for increasing the data base on adult Cambodians, Laotians, and Vietnamese. KEY WORDS: Asian Americans, Cambodians, Laotians, Vietnamese, culture, language, tobacco, smoking cessation, nicotine

Journal Article↗