Biomedical subjects

J L Kim

Publications and source records attributed to J L Kim.

46 records · Page 3Linked to original sources

PubMed1997

Renal ischemia-reperfusion injury does not induce pulmonary dysfunction in sheep.

It has already been shown that pulmonary injury is induced after intestinal or hind limb ischemia-reperfusion injury. The purpose of this study was to determine the effect of renal ischemia-reperfusion injury on the pulmonary system. We compared the pulmonary effects of 60 and 90 minutes ischemia followed by 24 hour reperfusion in sheep kidneys. Standard hemodynamic measurements, arterial and mixed venous blood gas analysis, urine output, creatinine clearance, and blood urea nitrogen concentration were measured at baseline, during ischemia and reperfusion periods. After 24 hours of reperfusion, animals were sacrificed and underwent autopsy with collection of samples for wet/dry lung-weight ratio, lung tissue conjugated dienes, and renal histology. As expected, renal ischemia resulted in an increased serum creatinine and blood urea nitrogen concentrations, decreased creatinine clearance, and histological evidence of renal damage. There was no evidence of pulmonary hypertension or hypoxemia during renal ischemia-reperfusion. There was also no significant difference in the wet/dry lung-weight ratios or lung tissue conjugated denies between the two ischemic groups (60 and 90 minutes) and nonischemic control group. These results suggest that renal ischemia-reperfusion injury was not associated with a significant degree of pulmonary dysfunction.

Animals↗

PubMed1996

Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide.

An estimated 1% of the global human population is infected by hepatitis C viruses (HCVs), and there are no broadly effective treatments for the debilitating progression of chronic hepatitis C. A serine protease located within the HCV NS3 protein processes the viral polyprotein at four specific sites and is considered essential for replication. Thus, it emerges as an attractive target for drug design. We report here the 2.5 angstrom resolution X-ray crystal structure of the NS3 protease domain complexed with a synthetic NS4A activator peptide. The protease has a chymotrypsin-like fold and features a tetrahedrally coordinated metal ion distal to the active site. The NS4A peptide intercalates within a beta sheet of the enzyme core.

Amino Acid Sequence↗

PubMed1996

Mutual hairless rat skin permeation-enhancing effect of ethanol/water system and oleic acid.

The mutual hairless rat skin permeation-enhancing effect of ethanol (EtOH)/water systems and oleic acid (OA) was investigated with model lipophilic (estradiol, progesterone, levonorgestrel) and hydrophilic drugs (zalcitabine, didanosine, zidovudine). The aqueous solubility and hairless rat skin permeation rate of each drug, saturated in various compositions of EtOH/water system (with and without OA), was determined at 37 degrees C. The hairless rat skin permeation rates of ethanol from EtOH/water systems (with and without OA) were also measured to investigate the skin permeation-enhancing mechanism of EtOH/water systems and OA. Both saturated solubility and steady-state permeation rates of each drug in EtOH/water systems increased exponentially as the volume fraction of ethanol increased, reached the maximum value, and then decreased with further increases in the ethanol volume fraction. Moreover, the hairless rat skin permeation rate of each drug had a good linear relationship with that of ethanol up to 70% (v/v) of ethanol in the EtOH/water system. The addition of OA in the EtOH/water system (70:30 and 60:40 for lipophilic and hydrophilic drugs, respectively) further enhanced the skin permeation rate of both ethanol and drugs. However, > 2.0% (v/v) OA was required to achieve the plateau level in the skin permeation rate of lipophilic drugs, whereas only 0.3% (v/v) OA was required for hydrophilic drugs. The skin permeation rate of ethanol also increased with the addition of OA in the EtOH/water systems (70:30 and 60:40), reached the plateau level with < 1.0% (v/v) OA, and did not significantly change with higher OA concentration. These results suggest that the addition of OA in the EtOH/water system is a useful method to enhance the hairless rat skin permeation rate of both hydrophilic and lipophilic drugs, with more enhancement for hydrophilic drugs.

Animals↗

PubMed1995

X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex.

The X-ray structure of the ternary complex of a calcineurin A fragment, calcineurin B, FKBP12, and the immunosuppressant drug FK506 (also known as tacrolimus) has been determined at 2.5 A resolution, providing a description of how FK506 functions at the atomic level. In the structure, the FKBP12-FK506 binary complex does not contact the phosphatase active site on calcineurin A that is more than 10 A removed. Instead, FKBP12-FK506 is so positioned that it can inhibit the dephosphorylation of its macromolecular substrates by physically hindering their approach to the active site. The ternary complex described here represents the three-dimensional structure of a Ser/Thr protein phosphatase and provides a structural basis for understanding calcineurin inhibition by FKBP12-FK506.

Amino Acid Sequence↗

PubMed1995

PCD/DCoH: more than a second molecular saddle.

Two recent crystal structures of the tetrameric pterin-4 alpha-carbinolamine dehydratase (PCD)/dimerization cofactor of HNF-1 (DCoH) protein provide fresh insights into how this multifunctional enzyme/transcriptional coactivator works.

Animals↗

PubMed1994

1.9 A resolution refined structure of TBP recognizing the minor groove of TATAAAAG.

The three-dimensional structure of a TATA box-binding protein (TBP) from Arabidopsis thaliana complexed with a fourteen base pair oligonucleotide bearing the Adenovirus major late promoter TATA element has been refined at 1.9 A resolution, giving a final crystallographic R-factor of 19.4%. Binding of the monomeric, saddle-shaped alpha/beta protein induces an unprecedented conformational change in the DNA. A detailed structural and functional analysis of this unusual protein-DNA complex is presented, with particular emphasis on the mechanisms of DNA deformation, TATA element recognition, and preinitiation complex assembly.

Amino Acid Sequence↗

PubMed1993

Co-crystal structure of TBP recognizing the minor groove of a TATA element.

The three-dimensional structure of a TATA-box binding polypeptide complexed with the TATA element of the adenovirus major late promoter has been determined by X-ray crystallography at 2.25 A resolution. Binding of the saddle-shaped protein induces a conformational change in the DNA, inducing sharp kinks at either end of the sequence TATAAAAG. Between the kinks, the right-handed double helix is smoothly curved and partially unwound, presenting a widened minor groove to TBP's concave, antiparallel beta-sheet. Side-chain/base interactions are restricted to the minor groove, and include hydrogen bonds, van der Waals contacts and phenylalanine-base stacking interactions.

Adenoviridae↗

PubMed1993

X-ray crystallographic studies of eukaryotic transcription factors.

Our X-ray crystallographic work on eukaryotic transcription factors traverses the entire length of a typical class II nuclear gene promoter, including the TATA-box-binding protein, two b/HLH/Z promoter proximal binding factors (Max and USF), and an enhancer-binding factor (HNF-3 gamma). These high-resolution studies of specific protein/DNA interactions will be extended to include homologous proteins complexed with similar oligonucleotides and a systematic examination of the roles of individual amino acids and bases implicated in specific DNA binding. In the longer term, we will turn our attention to the myriad of protein/protein interactions occurring within TFIID and the PIC, and between the PIC and factors binding to promoter proximal and distal enhancer elements.

Animals↗

PubMed1991

Responses of neurons in the ventromedial midbrain to noxious mechanical stimuli.

Neurons of the ventromedial midbrain in pentobarbital-anesthetized rats were examined by extracellular recording for responses to mechanical stimulation of the skin. Responses were absent from neurons clearly located in the interpeduncular nucleus (IPN) (n = 20), and from 92% of linear raphe (LR) neurons (n = 26). However, 37% of neurons in the ventral tegmental area of Tsai (VTA) (n = 38) and 63% of neurons in the small interfascicular nucleus (IF) (n = 9) were inhibited, often recovering with a delay of 1-2 min. A few cells (n = 4) were weakly excited in these 4 nuclei; none responded to innocuous mechanical stimulation of the skin. It is concluded that noxious cutaneous stimuli will not modify (by feedback) any influence of the IPN on pain perception, but could dampen behavior-reinforcing effects of the VTA and IF.

Animals↗

PubMedDate not supplied

Dosimetric properties of the newly developed KLT-300 (LiF:Mg,Cu,Na,Si) TL detector.

The dosimetric properties of the newly developed KLT-300 (KAERI LiF:Mg,Cu,Na,Si TL detector) in KAERI (Korea Atomic Energy Research Institute) were investigated. The sensitivity of the TL detector was about 30 times higher than that of the TLD-100 by light integration. In the study of the dose linearity of the detector, the dose response was very linear up to 10 Gy and a sublinear response was observed at higher doses. The energy response of the detector was studied for photon energies from 20 to 662 keV. The results show that a maximum response of 1.004 at 53 keV and a minimum response of 0.825 at 20 keV were observed. The reproducibility study for the TL detector was also carried out. The coefficients of variation for each detector separately did not exceed 0.016, and for all the 10 detectors collectively it was 0.0054. IEC Standard requires that the coefficient of variation shall not exceed 0.075. So, the reproducibility of this new TL detector sufficiently satisfied the IEC requirements. A detection threshold of the detector was investigated and found to be 70 nGy by Harshaw 4500 TLD Reader.

Copper↗