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Biomedical subjects

H Suh

Publications and source records attributed to H Suh.

At least 55 records · Page 3Linked to original sources
PubMed1999

Coordinate regulation of RAG1 and RAG2 by cell type-specific DNA elements 5' of RAG2.

RAG1 and RAG2 are essential for V(D)J recombination and lymphocyte development. These genes are thought to encode a transposase derived from a mobile genetic element that was inserted into the vertebrate genome 450 million years ago. The regulation of RAG1 and RAG2 was investigated in vivo with bacterial artificial chromosome (BAC) transgenes containing a fluorescent indicator. Coordinate expression of RAG1 and RAG2 in B and T cells was found to be regulated by distinct genetic elements found on the 5' side of the RAG2 gene. This observation suggests a mechanism by which asymmetrically disposed cis DNA elements could influence the expression of the primordial transposon and thereby capture RAGs for vertebrate evolution.

Animals↗
PubMed1999

Continued RAG expression in late stages of B cell development and no apparent re-induction after immunization.

Models of B-cell development in the immune system suggest that only those immature B cells in the bone marrow that undergo receptor editing express V(D)J-recombination-activating genes (RAGs). Here we investigate the regulation of RAG expression in transgenic mice carrying a bacterial artificial chromosome that encodes a green fluorescent protein reporter instead of RAG2. We find that the reporter is expressed in all immature B cells in the bone marrow and spleen. Endogenous RAG messenger RNA is expressed in immature B cells in bone marrow and spleen and decreases by two orders of magnitude as they acquire higher levels of surface immunoglobulin M (IgM). Once RAG expression is stopped it is not re-induced during immune responses. Our findings may help to reconcile a series of apparently contradictory observations, and suggest a new model for the mechanisms that regulate allelic exclusion, receptor editing and tolerance.

Alleles↗
PubMed1999

Secondary V(D)J recombination in B-1 cells.

B-1 B cells are a self-renewing population of B cells that differ from conventional B cells (B-2 cells) in that they are particularly predisposed to auto-antibody production. Although much is known about the signalling pathways that control B-1-cell growth and development, less is known about why these cells are prone to produce autoreactive antibodies. Here we show that B-1 cells, like germinal-centre B cells, can express recombinase-activating genes 1 and 2 (RAG1 and RAG2) and undergo secondary V(D)J recombination of immunoglobulin genes. In addition, B cells from autoimmune-prone NZB mice show high levels of RAG messenger RNA and recombination. We propose that secondary immunoglobulin-gene rearrangements outside organized lymphoid organs may contribute to the development of autoreactive antibodies.

Animals↗
PubMed1999

Dosage requirement of Pitx2 for development of multiple organs.

Pitx2 is a homeodomain transcription factor that is mutated in Rieger syndrome, a haploinsufficiency disorder affecting eyes and teeth. Pitx2 also has a postulated role in left-right axis determination. We assessed the requirements for Pitx2 directly by generating hypomorphic and null alleles. Heterozygotes for either allele have eye abnormalities consistent with Rieger syndrome. The ventral body wall fails to close in embryos homozygous for the null allele, leaving the heart and abdominal organs externalized and the body axis contorted. In homozygotes for either allele, the heart tube undergoes normal, rightward looping and the stomach is positioned normally. In contrast, homozygotes for both alleles exhibit right isomerization of the lungs. Thus, Pitx2 is required for left-right asymmetry of the lungs but not other organs. Homozygotes for either allele exhibit septal and valve defects, and null homozygotes have a single atrium proving that a threshold level of Pitx2 is required for normal heart development. Null homozygotes exhibit arrest of pituitary gland development at the committed Rathke pouch stage and eye defects including optic nerve coloboma and absence of ocular muscles. This allelic series establishes that Pitx2 is required for the development of mulitple organs in a dosage-sensitive manner.

Abnormalities, Multiple↗
PubMed1999

Evaluation of the degree of cross-linking in UV irradiated porcine valves.

A porcine heart valve was irradiated by Ultraviolet (UV) rays (10 W, 254 nm) for 2, 4, 8 and 24 hours at 4 degrees C to cross-link the structural collagen matrix. The degree of cross-linking was evaluated by assaying the released amount of hydroxyproline (Hyp) from the matrix, and comparing it with the positive controls of valves treated by glutaraldehyde (GA) solution (0.625 wt%) and the negative controls of non-treated fresh valves. The undigested weight ratio of the specimens increased by increasing the UV irradiation time. The undigested weight of the leaflets, tunica interna and tunica externa of the fresh, GA-treated and UV-irradiated specimens after collagenase digestion was compared. As UV irradiation increased, the amount of released hydroxyproline was gradually decreased until 8 hours of irradiation, after which the released hydroxyproline-reduction occurred slightly until 24 hours of irradiation time in this system. A total 47.68% of the hydroxyproline in the valve was cross-linked by UV irradiation after 24 hours, while 73.74% of the hydroxyproline in the positive control was crossed-linked. Light microscopic observation revealed that the typical crimp pattern of collagen fibers decreased and was rearranged into a dense flattened pattern as the UV irradiation induced interfibrilar cross-linking. GA-treated valves demonstrated a denser matrix pattern than the UV-irradiated specimens. Cross-linked collagenous tissue prepared by UV irradiation would be useful for improving durability and reducing the disadvantages related to using a chemical cross-linking agent.

Animals↗
PubMed1999

Viability and enzymatic activity of cryopreserved porcine heart valve.

Fibroblast viability of a natural tissue valve for replacing a defective heart valve through allograft or xenograft has been suggested to affect its clinical durability. In this study, the cell viability and enzymatic activity of porcine heart valve leaflets were examined in regard to concerning to the preservation process [variable warm ischemic time (WIT), cold ischemic time (CIT), and cryopreservation]. Porcine heart enblocs were obtained and valve dissection was performed after 2, 12, 24, or 36 hours, in respective groups A, B, C, and D, as WIT. Each group was stored for 24 hours as CIT and cryopreserved. Leaflets were dissected from a valved conduit after each process, and cell viability and enzymatic activity in the leaflet were investigated using trypan blue staining and API ZYM kits. WIT extension significantly decreased fibroblast viability (p < 0.05, 92.25 +/- 2.7% at 2 hours, 84.9 +/- 6.7% at 12 hours, 57.0 +/- 10.2% at 24 hours, 55.9 +/- 7.9% at 36 hours), while CIT for 24 hours was also influenced significantly (p < 0.05), whereas cryopreservation demonstrated no effect on cellular viability. In enzyme activity observation, several enzymes related to lipid or nucleotide degradation (esterase, esterase lipase, particularly phosphatase, phosphohydrolase) were remarkably changed following the valve-fabrication process. After 24 hours CIT, these enzymatic activities in groups B, C and D significantly increased, but the activities decreased after cryopreservation. Particularly, both the viability and enzymatic activity showed remarkable changes after CIT in group B (WIT = 12 hours). These results suggest that WIT is more important than CIT in maintaining viability of the valve, and that completing all the cryopreservation process within 12 hours after acquisition is recommended.

Animals↗
PubMed1999

Preclinical evaluation of prototype products.

Preclinical evaluation of medical devices (prototype products) offers the opportunity to investigate and study the intended use of device materials. Preclinical evaluation programs are designed to determine the efficacy, safety, and biocompatibility of biomaterials, prostheses, and medical devices. The purpose of safety testing is to determine if a material presents potential harm to the human; it evaluates the interaction of the material with the in vivo environment and determines the effect of the host on the implant. Preclinical evaluation is the determination of the ability of the prototype product to perform with appropriate host response in a specific application, considered from the perspective of human clinical use. Therefore, preclinical data should include materials science and engineering, biology, biochemistry, medicine, host reactions and their evaluation, the testing of biomaterials, and the degradation of materials in a biological environment.

Animals↗
PubMed1998

Ku80 is required for immunoglobulin isotype switching.

Isotype switching is the DNA recombination mechanism by which antibody genes diversify immunoglobulin effector functions. In contrast to V(D)J recombination, which is mediated by RAG1, RAG2 and DNA double-stranded break (DSB) repair proteins, little is known about the mechanism of switching. We have investigated the role of DNA DSB repair in switch recombination in mice that are unable to repair DSBs due to a deficiency in Ku80 (Ku80(-/-)). B-cell development is arrested at the pro-B cell stage in Ku80(-/-) mice because of abnormalities in V(D)J recombination, and there are no mature B cells. To reconstitute the B-cell compartment in Ku80(-/-) mice, pre-rearranged VB1-8 DJH2 (mu i) and V3-83JK2 (kappa i) genes were introduced into the Ku80(-/-) background (Ku80(-/-)mu i/+kappa i/+). Ku80(-/-)mu i/+ kappai/+ mice develop mature mIgM+ B cells that respond normally to lipopolysaccharide (LPS) or LPS plus interleukin-4 (IL-4) by producing specific germline Ig constant region transcripts and by forming switch region-specific DSBs. However, Ku80(-/-)mu i/+kappa i/+ B cells are unable to produce immunoglobulins of secondary isotypes, and fail to complete switch recombination. Thus, Ku80 is essential for switch recombination in vivo, suggesting a significant overlap between the molecular machinery that mediates DNA DSB repair, V(D)J recombination and isotype switching.

Animals↗
PubMed1998

Regulation of smooth muscle cell proliferation using paclitaxel-loaded poly(ethylene oxide)-poly(lactide/glycolide) nanospheres.

Available data suggest that drugs should be delivered to a vascular lesion at a high concentration over an extended period of time to control vascular smooth muscle cell (VSMC) proliferation. This study was undertaken to formulate a paclitaxel, an antimicrotubule agent, into a biodegradable poly (ethylene oxide)-poly(lactide/glycolide) (PEO-PLGA) nanosphere as a sustained drug delivery system and to study its effects on VSMC in culture. The paclitaxel-loaded nanospheres (PT/NS), prepared by an emulsion-solvent evaporation method, had an average diameter of approximately 150 nm and showed a sustained release profile over 4 weeks. The PT/NS exhibited antiproliferative effects comparable to those observed with free paclitaxel. The cellular internalization of nanospheres was visualized using confocal fluorescence microscopy, and from a flow cytometry study the progressive cellular uptake profile, uptake inhibition at low temperature, and saturation uptake kinetics (concentration dependency) were observed. These suggest that (adsorptive) pinocytosis is a major uptake mechanism of the nanospheres. The sustained drug release profile and cellular internalization results suggest that nanospheres loaded with paclitaxel may potentially be used as an endocytizable, local sustained drug delivery system for the prevention of restenosis.

Animals↗
PubMed1998

Recent advances in biomaterials.

Biomaterials for medical use have been developed in accordance with progress of the fields of medicine, biochemistry, material science, and pharmaceutics. Advances in the medicine have changed the concept of surgery from the deletion of damage tissue for the preservation of the remaining healthy tissue to the reconstruction or replacement of damaged tissue by promoting regeneration of the natural tissue. All the materials used in medicine should be biocompatible. Conventional materials such as metals, ceramics, and synthetic polymers are usually bioinert and support the structural defects. But recently introduced biomaterials are designed to provide biological functions as much a possible by mimicking natural tissue structures.

Biocompatible Materials↗
PubMed1998

Use of Amuchina 50% solution versus povidone-iodine 10% solution for transfer-set change in peritoneal dialysis patients.

The goal of this study was to compare the safety and efficacy of Amuchina 50% solution versus that of povidone-iodine 10% solution for transfer-set change in peritoneal dialysis (PD) patients in a tertiary referral university hospital. The transfer sets were changed using povidone-iodine 10% solution as disinfectant prior to March 1995. Thereafter Amuchina 50% solution was used. Thus data were collected on all the transfer sets changed between January 1993 and August 1997. Amuchina is an electrolytic chloroxidizer. Chlorine is the active ingredient with a pH of 9.5-10.5. Amuchina 50% solution contains chlorine (0.55%). One hundred ninety-nine transfer sets were changed using povidone-iodine 10% solution in 60 PD patients from January 1993 to March 1995. One hundred twenty-eight transfer sets were changed using Amuchina 50% solution in 65 patients from April 1995 to August 1997. The soaking times and nursing times were 2 and 5 minutes, respectively, with Amuchina, and 10 and 20 minutes, respectively, with povidone-iodine 10%. No episode of peritonitis occurred related to transfer-set change in either group. The transfer-set change using Amuchina 50% solution is safe and cost-effective in PD patients.

Anti-Infective Agents, Local↗
PubMed1997

V(D)J recombination in mature B cells: a mechanism for altering antibody responses.

The clonal selection theory states that B lymphocytes producing high-affinity immunoglobulins are selected from a pool of cells undergoing antibody gene mutation. Somatic hypermutation is a well-documented mechanism for achieving diversification of immune responses in mature B cells. Antibody genes were also found to be modified in such cells in germinal centers by recombination of the variable (V), diversity (D), and joining (J) segments. The ability to alter immunoglobulin expression by V(D)J recombination in the selective environment of the germinal center may be an additional mechanism for inactivation or diversification of immune responses.

Animals↗
PubMed1997

Anti-angiogenic activity of ursodeoxycholic acid and its derivatives.

Ursodeoxycholic acid (UDCA) and its derivatives were examined for anti-angiogenic activities by using the chick embryo chorioallantoic membrane (CAM) assay. The presence of UDCA or its derivatives inhibited angiogenesis in a dose-dependent manner; the dose required for half-maximal inhibition (ID50) was 4 microg per CAM for UDCA. The conjugate forms of UDCA with glycine methyl ester (HS-1030), L-leucine benzyl ester (HS-1068) and L-leucine methyl ester (HS-1133) were showing ID50 of 0.09, 0.08 and 0.6 microg per CAM, respectively. Also, the effect of UDCA and its derivatives on the viability of calf pulmonary artery endothelial (CPAE) cells was examined. Among them, HS-1030 effectively reduced the viability of CPAE cells in a concentration-dependent manner. Based on these results, we speculated that HS-1030 might be a promising candidate as angiogenesis inhibitor for use in the management of diseases accompanied by uncontrolled angiogenesis including solid tumor.

Animals↗
PubMed1997

Percutaneous absorption and disposition studies of methotrexate in rabbits and rats.

The absorption and disposition of methotrexate (MTX) in the plasma, synovial fluid (SF), skin, and muscle tissue were studied following administration of a topical MTX gel in rabbits and rats. In rabbits, MTX concentrations in the plasma increased steadily toward the peak (5.9 +/- 2.8 ng mL-1) which appeared at approximately 2 h postdose and declined with the elimination half-life of 4.48 +/- 1.74 h. At 1 h after the topical dose, the MTX concentrations in the skin (49.0 +/- 19.8 micrograms g-1), muscle (12.7 +/- 3.3 ng g-1), and SF (19.2 +/- 10.1 ng g-1) underneath the dosed stifle joint were significantly higher (p < 0.05) than those of the untreated stifle joint, indicating the potential therapeutic value of topical delivery of MTX for rheumatoid arthritis. A large fraction (approximately 59%) of MTX which was found in the skin at 1 h postdose was present in the stratum corneum, indicating its extensive binding capacity for MTX. The MTX concentrations in the muscle and SF of the dosed stifle joint at 1 h postdose were 1.8 and 2.6 times higher than those in the dosed elbow joint, respectively, reflecting the effect of dose site on the permeation of MTX. Using a new filter paper method, the amounts of SF obtained from the elbow and stifle joints of four rabbits were 26.3 +/- 8.3 and 48.8 +/- 5.2 mg, respectively. A significant enhancer effect of N,N-diethyl-n-toluamide (DEET) on the disposition of MTX in the stratum corneum of rabbit ear was observed (p < 0.05) by the tape-stripping method. In rats, the gel containing 4% DEET resulted in a twofold increase in the permeation of MTX into the muscle over the 4 h period postdose. A modified HPLC method with a linear calibration curve (r > 0.999) over the range of 2-50 ng mL-1. quantitation limit of 0.5 ng mL-1, and mean recovery of approximately 87% was used for the quantitation of MTX in the tissue and fluid samples.

Animals↗