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Biomedical subjects

Young-Mi Kim

Publications and source records attributed to Young-Mi Kim.

26 records · Page 2Linked to original sources

Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1.

Endostatin, a fragment of collagen XVIII, is a potent anti-angiogenic protein, but the molecular mechanism of its action is not yet clear. We examined the effects of endostatin on the biological and biochemical activities of vascular endothelial growth factor (VEGF). Endostatin blocked VEGF-induced tyrosine phosphorylation of KDR/Flk-1 and activation of ERK, p38 MAPK, and p125(FAK) in human umbilical vein endothelial cells. Endostatin also inhibited the binding of VEGF(165) to both endothelial cells and purified extracellular domain of KDR/Flk-1. Moreover, the binding of VEGF(121) to KDR/Flk-1 and VEGF(121)-stimulated ERK activation were blocked by endostatin. The direct interaction between endostatin and KDR/Flk-1 was confirmed by affinity chromatography. However, endostatin did not bind to VEGF. Our findings suggest that a direct interaction of endostatin with KDR/Flk-1 may be involved in the inhibitory function of endostatin toward VEGF actions and responsible for its potent anti-angiogenic and anti-tumor activities in vivo.

Antineoplastic Agents↗

Holmium-166-DTPA as a liquid source for endovascular brachytherapy.

Liquid radiation sources with beta emitters have advantages of accurate positioning and uniform dose distribution to the vessel walls to prevent the restenosis of coronary artery. As a liquid radiation source, 166Ho-DTPA was prepared and evaluated its in-vivo pharmacokinetic behavior through animal studies.166Ho-DTPA was prepared by simple mixing the Holmium with DTPA at room temperature. The radiolabelling yield was 100% when the DTPA/Holmium molar ratio was >2. Radiolabelling of 166Ho-DTPA was not dependent on the pH range of 1.7-7.5. High radiochemical stability (>98%) was maintained over a period of 6 hours even with a radioactivity ( approximately 11.1 GBq/12 mg of DTPA) stored at room temperature. Biodistribution of 166Ho-DTPA in rats and gamma camera images in rabbits showed that 166Ho-DTPA was quickly excreted via the urinary system. The average of T(max) and T(1/2) of 166Ho-DTPA in the kidneys of rabbits were 3.71 +/- 1.18 min and 9.15 +/- 3.15 min. 166Ho-DTPA is a potential liquid radiation source for radiation brachytherapy to prevent the restenosis of the coronary artery using a liquid-filled balloon.

Animals↗

HFR1, a phytochrome A-signalling component, acts in a separate pathway from HY5, downstream of COP1 in Arabidopsis thaliana.

HFR1, a basic helix-loop-helix protein, is known to be required for a subset of phytochrome A (phyA)-dependent photoresponses. To investigate the role of HFR1 in light signalling, we have examined the genetic interaction between HFR1 and HY5, a positive regulator of light signalling, and COP1, a repressor of photomorphogenesis. Double mutant analysis suggests that HFR1 mediates phyA-dependent inhibition of hypocotyl elongation independently of HY5. HFR1 was shown to be necessary for a subset of cop1-triggered photomorphogenic phenotypes in the dark, including inhibition of hypocotyl elongation, gravitropic hypocotyl growth, and expression of the light-inducible genes CAB and RBCS. Phenotypic analysis of the triple mutant cop1hy5hfr1 indicated that both HFR1 and HY5 are required for cop1-mediated photomorphogenic seedling development in darkness, consistent with their additive roles in phyA-dependent signalling. Taken together, these results suggest that HFR1 might act downstream of COP1, in a separate pathway from HY5, to mediate photomorphogenesis in Arabidopsis.

Arabidopsis↗

Impact of supervision and self-assessment on doctor-patient communication in rural Mexico.

OBJECTIVE: To determine whether supervision and self-assessment activities can improve doctor-patient communication. SETTING AND PARTICIPANTS: Six supervisors, 60 doctors in their last year of training, and 232 primary health care patients at rural health clinics in Michoacan, Mexico. DESIGN: The main evaluation compared post-intervention measures in control and intervention groups. A small panel study also examined changes from baseline to post-intervention rounds in both groups. INTERVENTION: Over a 4-month period, specially trained supervisors added 1 hour of supervision on interpersonal communication and counseling (IPC/C) to regular site visits. Doctors, who had received prior IPC/C training, periodically audiotaped and assessed their own consultations. MAIN OUTCOME MEASURES: These comprised frequency of doctors' facilitative communication, doctors' biomedical information-giving, and patients' active communication. RESULTS: The performance of all doctors improved markedly over the study period, but gains in facilitative communication and information-giving were significantly greater in the intervention than the control group. No single component of the intervention was responsible for the improvement; it resulted from the combination of activities. The doctors appreciated the more supportive relationship with supervisors that resulted from the intervention and found listening to themselves on audiotape a powerful, although initially stressful, experience. CONCLUSION: Supportive supervision and self-assessment activities can reinforce IPC/C training, prompt reflection and learning, and help novice doctors improve their interpersonal communication skills.

Communication↗

Measuring the quality of supervisor-provider interactions in health care facilities in Zimbabwe.

OBJECTIVE: Measuring performance is the first step on the road to improving it. This report presents the results of an exploratory study sponsored by the Quality Assurance (QA) Project to describe and quantify the quality of supervisor-provider interactions in health care facilities in Zimbabwe in 1999. Supervisors were district and municipal nursing officers who are responsible for guiding, assisting, and motivating health providers at government and missionary health facilities. DESIGN: The study's design was qualitative. It involved the triangulation of data from various sources: structured observations of supervisors, audiotaping of supervisor-provider interactions, recording of all supervisory activities, and interviews with supervisors and supervisees. A team composed of current and past supervisors, along with researchers, determined the supervisory practices that would be measured. STUDY PARTICIPANTS: Sixteen district-level government, municipality, and Zimbabwe National Family Planning Council supervisors from four provinces participated in the study. RESULTS: The study found that supervisors devoted <5% of their time to patient care issues. The supervisors' main strengths were in giving feedback on technical standards, discussing and analyzing data, and developing a rapport with the providers. They were most deficient in making suggestions, seeking client input, problem solving with the providers, and building on previous (and future) supervisory visits. None of the supervisors observed achieved the threshold set in advance by the team for exemplary performance. CONCLUSION: The study concludes with recommendations to the Ministry of Health and Child Welfare on how the quality of supervision in Zimbabwe could be improved.

Adult↗

Parental decisions of prenatally detected sex chromosome abnormality.

Because of the widespread use of amniocentesis, the prenatal recognition of sex chromosome abnormality (SCA) has become increasingly common. Recent literature provided an insight into the understanding of the natural history and prognosis for individuals with SCA. Our study was designed to review the parental decision on pregnancy with SCA. Over the last 10 yr, we diagnosed 38 cases (0.50%) with SCA out of 7,498 prenatal cases. We reviewed the records and the results of the pregnancies. We included the cases (n=25) of apparently normal anatomic fetus to analyze the factors influencing parental decision. We excluded 13 cases with obvious anomaly or presumably bad outcome. Fifteen (60%) couples continued their pregnancies and ten (40%) terminated theirs. Nine couples (64%) out of fourteen mosaicism cases continued their pregnancies. All five pregnancies assisted by reproductive technique continued their pregnancies. More pregnancies were continued when counseling was done by an MD geneticist rather than by an obstetrician. A significant trend was observed with a higher rate of pregnancy continuation in recent years. The genetic counseling is important to give appropriate information to the parents. Establishing guidelines and protocols will help both obstetricians and parents to make a decision.

Chromosome Aberrations↗

Amniotic fluid interphase fluorescence in situ hybridization (FISH) for detection of aneuploidy; experiences in 130 prenatal cases.

The major aneuploidies diagnosed prenatally involve the autosomes 13, 18, 21, and sex chromosomes X and Y. Fluorescence in situ hybridization (FISH) allows rapid analysis of chromosome copy number in interphase cells. We retrospectively reviewed 130 amniotic fluid interphase FISH analyses from January 1997 to December 2001. The review was done in order to assess the role of interphase FISH among the patients who were at the risk of fetal aneuploidies. The sample was considered to be aneuploid when 70% of or more than the total number of hybridized nuclei displayed the same abnormal hybridization pattern for a specific probe. All of 130 cases but one met the criteria. The results were considered as informative and they were obtained in 24-48 hr. The overall detection rate for aneuploidies was 100% (2 cases of trisomy 21, 2 cases of trisomy 18, and 1 case of Turner syndrome). In comparison to cytogenetics, the rates of both sensitivity and specificity were 100%. The experiment demonstrates that FISH can provide a rapid and accurate clinical method for prenatal identification of chromosome aneuploidies. The experiment can also serve as an adjunctive test to help cytogenetics to reduce significant amount of emotional stress of patients and physicians through early decision making process.

Adult↗

TNF-related activation-induced cytokine (TRANCE) induces angiogenesis through the activation of Src and phospholipase C (PLC) in human endothelial cells.

Angiogenesis is an essential step for many physiological and pathological processes. Tumor necrosis factor (TNF) superfamily cytokines are increasingly recognized as key modulators of angiogenesis. In this study, we tested whether TNF-related activation-induced cytokine (TRANCE), a new member of the TNF superfamily, possesses angiogenic activity in vitro and in vivo. TRANCE stimulated DNA synthesis, chemotactic motility, and capillary-like tube formation in primary cultured human umbilical vein endothelial cells (HUVECs). Both Matrigel plug assay in mice and chick chorioallantoic membrane assay revealed that TRANCE potently induced neovascularization in vivo. TRANCE had no effect on vascular endothelial growth factor (VEGF) expression in HUVECs and TRANCE-induced angiogenic activity was not suppressed by VEGF-neutralizing antibody, implying that TRANCE-induced angiogenesis may be the result of its direct action on endothelial cells. TRANCE evoked a time- and dose-dependent activation of the mitogen-activated protein kinases ERK1/2 and focal adhesion kinase p125(FAK) in HUVECs, which are closely linked to angiogenesis. These signaling events were blocked by the Src inhibitor PP1 or the phospholipase C (PLC) inhibitor. Furthermore, these inhibitors and the Ca(2+) chelator BAPTA-AM suppressed TRANCE-induced HUVEC migration. These results indicate that the angiogenic activity of TRANCE is mediated through the Src-PLC-Ca(2+) signaling cascade upon receptor engagement in endothelial cells, suggesting the role of TRANCE in neovessel formation under physiological and pathological conditions.

Calcium↗