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Biomedical subjects

K Choi

Publications and source records attributed to K Choi.

At least 37 records · Page 2Linked to original sources

Basic fibroblast growth factor positively regulates hematopoietic development.

Recently identified BLast Colony Forming Cells (BL-CFCs) from in vitro differentiated embryonic stem (ES) cells represent the common progenitor of hematopoietic and endothelial cells, the hemangioblast. Access to this initial cell population committed to the hematopoietic lineage provides a unique opportunity to characterize hematopoietic commitment events. Here, we show that BL-CFC expresses the receptor tyrosine kinase, Flk1, and thus we took advantage of the BL-CFC assay, as well as fluorescent activated cell sorter (FACS) analysis for Flk1(+) cells to determine quantitatively if mesoderm-inducing factors promote hematopoietic lineage development. Moreover, we have analyzed ES lines carrying targeted mutations for fibroblast growth factor receptor-1 (fgfr1), a receptor for basic fibroblast growth factor (bFGF), as well as scl, a transcription factor, for their potential to generate BL-CFCs and Flk1(+) cells, to further define events leading to hemangioblast development. Our data suggest that bFGF-mediated signaling is critical for the proliferation of the hemangioblast and that cells expressing both Flk1 and SCL may represent the hemangioblast.

Activins↗

Complications of buttress plate stabilization of cervical corpectomy.

STUDY DESIGN: A retrospective analysis of 14 patients treated with cervical corpectomy and buttress plate fixation. OBJECTIVES: To determine the complications of buttress plate fixation following multilevel cervical corpectomies. SUMMARY OF BACKGROUND DATA: Buttress plate fixation of multilevel cervical corpectomy has recently been reported. Biomechanical data suggests that it is preferable to long plates spanning the entire corpectomy site. There are no clinical studies that have specifically addressed the complications of this type of plate fixation. METHODS: The records and radiographs of all patients who had undergone cervical buttress plate fixation following anterior cervical corpectomy for myelopathy were independently reviewed. Twelve of the patients had three-level corpectomies and two had two-level corpectomies. All patients had placement of a short plate at the inferior end of the construct with sufficient overhang to act as a buttress against graft extrusion. Three patients underwent posterior cervical fusion in addition to the anterior procedure. RESULTS: Graft extrusion. One patient had complete graft extrusion on the third post-operative night. A second patient who had undergone circumferential fusion had minimal plate dislodgement secondary to graft settling. Pseudarthrosis. Three patients had pseudarthroses. Two of these required revision posterior surgery. Neurologic. None of the patients suffered neurologic complications. With the exception of the one patient who died, the rest of the patients all improved by at least one Nurick grade. CONCLUSION: The most catastrophic complication in the present series was plate dislodgement causing airway compromise and eventually resulting in death. Surgeons who utilize these types of buttress plates without additional posterior instrumentation should be aware of the potential complications of buttress plate fixation.

Adult↗

Combinatorial Methods for the Synthesis of Aluminophosphate Molecular Sieves.

Automatic dispensing of reagents into autoclave blocks followed by synthesis, isolation, and automated structure analysis with X-ray diffractometry represents an efficient methodology for the combinatorial synthesis of microporous materials. The figure shows a typical diffractogram of as-synthesized AFI-type molecular sieves taken with a CCD camera.

Journal Article↗

In vitro hematopoietic and endothelial potential of flk-1(-/-) embryonic stem cells and embryos.

Mice deficient in the Flk-1 receptor tyrosine kinase are known to die in utero because of defective vascular and hematopoietic development. Here, we show that flk-1(-/-) embryonic stem cells are nevertheless able to differentiate into hematopoietic and endothelial cells in vitro, although they give rise to a greatly reduced number of blast colonies, a measure of hemangioblast potential. Furthermore, normal numbers of hematopoietic progenitors are found in 7.5-day postcoitum flk-1(-/-) embryos, even though 8. 5-day postcoitum flk-1(-/-) embryos are known to be deficient in such cells. Our results suggest that hematopoietic/endothelial progenitors arise independently of Flk-1, but that their subsequent migration and expansion require a Flk-1-mediated signal.

Animals↗

Release of renal dipeptidase from rabbit renal proximal tubules and its inhibition by gentamicin.

Effects of several drugs on rabbit renal proximal tubules were examined for the applicability of renal dipeptidase (RDPase, EC 3. 4. 13. 11) release as a model system to study nephrotoxicity. The proximal tubule prepared by the method of Taub (1990) released RDPase spontaneously in the control experiment which was confirmed by Western blotting. RDPase was also released from cisplatin, lipopolysaccharide (LPS), and indomethacin-treated tubules. Gentamicin inhibited RDPase release in a concentration-dependent manner. This RDPase release system may not be a general model to screen nephrotoxicity but could be a useful source of RDPase purification in a simple and inexpensive way.

Animals↗

Optimal operating parameters in the composting of swine manure with wastepaper.

A series of experiments were conducted to determine the optimal conditions for composting of swine manure and wastepaper. The aeration rate and mixing ratio were the variables investigated. In the first study (Study-1), four experiments each with the same mixing ratio but a different aeration rate were carried out. In the second study (Study-2), different mixing ratios were investigated, each however with the same aeration rate which was found to be optimal from Study-1. Composting efficiencies were evaluated on the temperature profile and the reduction of C/N ratio. From the aeration rates of 200, 500, 1000, and 1500 mL/min.kg_vs that were evaluated, the aeration rate of 500 mL/min.kg_vs and higher showed good results. In Study-2, where the initial C/N ratios were 20, 25, 30, and 35 respectively, the C/N ratio of 30 was found to be optimal. In conclusion, the composting of swine manure with the amendment of wastepaper was best carried out at the aeration of > 500 mL/min.kg_vs and C/N ratio of 30.

Air↗

Acute bereavement care in the emergency department: does the professional-supported volunteers model work?

The aims of our study were to study the early impact of bereavement and to evaluate the effectiveness of the bereavement care given by our multidisciplinary team to close relatives of a sudden death, measured by the intensity of grief reaction (Texas Revised Inventory of Grief). The study sample consisted of close relatives of patients certified dead at the accident and emergency department (AED) between March 1996 and February 1997. The relatives received immediate care at the AED and were supported continually by the members of the bereavement care team. The control sample (without acute bereavement care) consisted of close relatives contacted by the liaison nursing officer in the previous year. The intensity of grief reactions were assessed by the volunteer grief counsellors at 6 months. The mean score of the intensity of grief reactions were 41.8 and 34.6 in the control (n = 11) and study (n = 18) groups respectively among high risk sample (p = 0.04). However, in the low risk sample, the mean scores were 35.3 and 30.2 in the control (n = 18) and study (n = 25) groups respectively (p = 0.11). Our study suggests that the bereavement care was especially effective in reducing the intensity of the grief at 6 months in the high risk group.

Adolescent↗

Generation of a primitive erythroid cell line and promotion of its growth by basic fibroblast growth factor.

An immortalized cell line representing the primitive erythroid (EryP) lineage was established from in vitro-differentiated progeny (embryoid bodies [EBs]) of embryonic stem (ES) cells using a retroviral insertional mutation, and has been termed EB-PE for embryoid body-derived primitive erythroid. Even though EB-PE cells are immortalized, they show characteristics of normal EryP cells, such as gene expression and growth factor dependency. In addition, EB-PE cells can differentiate further in culture. Investigation of growth factor requirements of EB-PE cells showed that basic fibroblast growth factor (bFGF) and erythropoietin (Epo) play unique roles in EB-PE proliferation and differentiation. While bFGF was a strong mitogen, Epo was required for both proliferation and differentiation. The unique proliferative response to bFGF coincided with upregulation of its receptor, fibroblast growth factor receptor (fgfr-1), and downregulation of erythropoietin receptor (EpoR) gene expression. Studies of primary EryP cells derived from early EBs, when tested in a colony-formation assay, also provided evidence for the mitogenic role of bFGF in concert with Epo.

Animals↗

Production and characterization of monoclonal antibodies to oxidized LDL.

Oxidized low density lipoprotein (LDL) seems to take a part in atherogenesis through direct interactions with macrophages, endothelial cells, and smooth muscle cells, and is thought to participate in renal glomerular injury. For the purpose of illustrating the role of oxidized LDL in the human diseases, monoclonal antibodies were developed and characterized, recognizing oxidized LDL-specific epitopes that do not exist on native LDL. LDL was oxidized by the incubation with CuSO4, and used as immunogen. Splenocytes from the immunized mouse and mouse myeloma cells were fused to produce hybridomas, which were screened for the secretion of oxidized LDL-specific antibodies. Immunoblot analysis and binding affinity assay showed that these monoclonal antibodies recognize malondialdehyde-conjugated peptide epitopes.

Antibodies, Monoclonal↗

Magnetic resonance studies of intramuscular interferon beta-1a for relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group.

The Multiple Sclerosis Collaborative Research Group trial was a double-blind, randomized, multicenter, phase III, placebo-controlled study of interferon beta-1a (IFNbeta-1a; AVONEX) in relapsing forms of multiple sclerosis. Initial magnetic resonance imaging results have been published; this report provides additional results. Treatment with IFNbeta-1a, 30 microg once weekly by intramuscular injection, resulted in a significant decrease in the number of new, enlarging, and new plus enlarging T2 lesions over 2 years. The median increase in T2 lesion volume in placebo and IFNbeta-1a patients was 455 and 152 mm3, respectively, at 1 year and 1,410 and 628 mm3 at 2 years, although the treatment group differences did not reach statistical significance. For active patients, defined as those with gadolinium enhancement at baseline, the median change in T2 lesion volume in placebo and IFNbeta-1a patients was 1,578 and -12 mm3 and 2,980 and 1,285 mm3 at 1 and 2 years, respectively. Except for a minimal correlation of 0.30 between relapse rate and the number of gadolinium-enhanced lesions, correlations between MR and clinical measures at baseline and throughout the study were in general poor. Once weekly intramuscular IFNbeta-1a appears to impede the development of multiple sclerosis lesions at an early stage and has a favorable impact on the long-term sequelae of these inflammatory events as indicated by the slowed accumulation of T2 lesions.

Brain↗

Orbital subperiosteal hematoma, cholesterol granuloma, and infection. Evaluation with MR imaging and CT.

Orbital subperiosteal space, a potential space, is an important entity due to its unique anatomy and susceptibility to various pathologic processes. CT scan and MR imaging are important tools in the diagnosis of orbital subperiosteal hematomas, cholesterol granulomas, and infections. MR imaging has emerged as the modality of choice in the evaluation of hematomas and infections of this space due to its multiplanar capability and various imaging sequences giving better information. High-resolution CT scan offers good differentiation in most of these cases. Osseous changes in a cholesterol granuloma is better seen in CT scan, although MR imaging offers better differentiation from epidermoid or dermoid cysts and other subperiosteal process, as well as lacrimal fossa lesions. Subperiosteal abscesses are best evaluated using MR imaging.

Abscess↗

A common precursor for hematopoietic and endothelial cells.

Embryonic stem cell-derived embryoid bodies contain a unique precursor population which, in response to vascular endothelial growth factor, gives rise to blast colonies in semi-solid medium. Upon transfer to liquid culture with appropriate cytokines, these blast colonies generate both hematopoietic and adherent, stromal-type cells. Cells within the adherent population display characteristics of endothelial lineage including the expression of CD31, flk-1, flt-1, tie-2, the capacity to take up acetylated LDL and the presence of cytoplasmic Weibel-Palade bodies. Mixing studies demonstrated that the hematopoietic and endothelial precursors within the blast colonies develop from the same cell, the blast colony-forming cell. Kinetic analysis showed that the blast colony-forming cell represents a transient cell population that develops early and is lost quickly during embryoid body development. These findings provide strong evidence that the blast colony-forming cell represents the long-hypothesized hemangioblast, the common precursor of the hematopoietic and endothelial lineages.

Animals↗

Hemangioblast development and regulation.

Hematopoietic and endothelial cell lineages are the first to mature from mesoderm in the developing embryo. However, little is known about the molecular and (or) cellular events leading to hematopoietic commitment. The recent applications of technology utilizing gene targeted mice and the employment of many available in vitro systems have facilitated our understanding of hematopoietic establishment in the developing embryo. It is becoming clear that embryonic hematopoiesis occurs both in the extra-embryonic yolk sac and within the embryo proper in the mouse. The existence of the long pursued hemangioblast, a common progenitor of hematopoietic and endothelial cells, is now formally demonstrated. Based on this new information, many studies are being conducted to understand hematopoietic commitment events from mesoderm. In this review, we will first discuss the establishment of the hematopoietic system with special emphasis on the most primitive hematopoietic committed cells, the hemangioblast. We will then discuss mesoderm-inducing factors and their possible role in hematopoietic lineage commitment.

Animals↗

A common precursor for primitive erythropoiesis and definitive haematopoiesis.

The generation of blood cells, haematopoiesis, in the mouse embryo begins with the development of primitive nucleated erythroid cells in the yolk sac followed by the appearance of precursors for multiple definitive haematopoietic lineages. The later developing lineages arise from multipotential stem cells, but the relationship of primitive erythroid cells to these other haematopoietic populations is unknown. Using an in vitro embryonic stem (ES) cell differentiation system, we show that primitive erythrocytes and other haematopoietic lineages arise from a common multipotential precursor that develops within embryoid bodies generated from differentiated ES cells. In response to vascular endothelial growth factor and c-kit ligand these precursors give rise to colonies containing immature cells (blasts) expressing marker genes characteristic of haematopoietic precursors. Many blast colonies also expressed betaH1 and beta major globins but not Brachyury, a mesodermal marker. Kinetic analysis demonstrated that the blast colony-forming cells represent a transient population, preceding the establishment of the primitive erythroid and other lineage-restricted precursors. This precursor population may represent the earliest stage of embryonic haematopoietic commitment.

Animals↗

A sensitive ocular perfusion apparatus measuring outflow facility.

PURPOSE: To build an improved apparatus for measuring outflow facility by one- and two-level, constant pressure perfusion. METHODS: A computer-controlled and -monitored tower adjusts the height of a fluid reservoir by a stepper motor every 5 min, to keep intraocular pressure (IOP) constant at one or two desired pressure levels (e.g. 2.5 and 12.0 mm Hg above the spontaneous IOP). The fluid flow rate is calculated by the equation Q = (Pres - IOP)/R, where Pres is the pressure of the reservoir as calculated by the term "pgh," h being the height of the reservoir, measured by the rotation of stepper motor, g, the gravity constant, and p, the fluid density. IOP is measured by the transducer, and R is the resistance of 180 microns tubing. Outflow facility is calculated by delta Q/ delta P. delta Q is the difference between flow rate at the two pressure levels, and delta P is the intraocular pressure difference. Perfusion was performed on live albino rat eyes by the two-level constant pressure technique, and on artificial steel eyes at a single constant pressure perfusion (20 mm Hg). RESULTS: Outflow facility of albino rat eyes and artificial steel eyes perfused for 40 and 30 min, respectively was 0.0507 +/- 0.0039 microliter/min/mm Hg and 0.3546 +/- 0.0034 microliter/min/mm Hg (mean +/- SD), respectively. CONCLUSIONS: Our perfusion apparatus is highly stable, sensitive, and capable of measuring subtle changes in outflow facility in vivo and in vitro.

Animals↗

Flk-1 expression defines a population of early embryonic hematopoietic precursors.

We have investigated the expression pattern of the Flk-1 receptor tyrosine kinase in mouse embryonic and fetal hematopoietic tissues as well as on hematopoietic precursor cells derived from these tissues. RNA analysis indicated that flk-1 was expressed in the yolk sac at day 10 of gestation, in the whole embryo at day 10 and 12 of gestation, in the liver throughout fetal life and in embryoid bodies (EBs) generated from ES cells differentiated in culture. Flk-1 message was also detected in erythroid and macrophage colonies generated from precursors of yolk sac, fetal liver, adult marrow and EB origin. Using an antibody directed against the extracellular portion of the molecule we have found that up to 50% of cells from EBs differentiated for 4 days express Flk-1. Following the development of this early Flk-1+ population the number of receptor-positive cells declines progressively to represent less than 5% of the EBs by day 12 of differentiation. Kinetic analysis revealed that the establishment of the EB Flk-1+ population precedes the development of cells which express CD34, Ly6A (Sca-1) and AA4.1. Cell sorting experiments demonstrated that all day-4 EB-derived hematopoietic precursors are Flk-1+ whereas greater than 95% of those found within the day-12 EBs are Flk-1-, suggesting that the precursor population which expresses this receptor represents an early but transient wave of hematopoietic development. Analysis of yolk sac and whole embryos at day 8.5 of gestation revealed a small but distinct Flk-1+ population that contained hematopoietic precursors. Day-12.5 fetal liver contained few Flk-1+ cells that showed little hematopoietic potential. Together these findings indicate that Flk-1 is expressed on an early population of hematopoietic precursors that may represent the onset of embryonic hematopoiesis.

Animals↗