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Biomedical subjects

J G Kim

Publications and source records attributed to J G Kim.

At least 55 records · Page 3Linked to original sources

GM-CSF-based mobilization effect in normal healthy donors for allogeneic peripheral blood stem cell transplantation.

It is important to optimize methods to mobilize hematopoietic stem cells into peripheral blood (PB) for successful allogeneic peripheral blood stem cell (PBSC) transplantation. Our primary intent was to investigate the role of GM-CSF for mobilization in normal healthy donors and to compare its efficacy in mobilizing stem cells alone, in concurrent combination and in sequential combination with G-CSF in this study. We analyzed the results of the PBSC harvest through large volume leukapheresis from 48 normal healthy donors mobilized by three different regimens including GM-CSF. Donors were assigned sequentially to one of the following regimens for mobilization: GM-CSF 10 microg/kg/day alone (group 1, n = 9); concurrent combination (group 2, n = 20) of G-CSF 5 microg/kg/day and GM-CSF 5 microg/kg/day; sequential combination (group 3, n = 19) of GM-CSF alone 10 microg/kg/day for 3 days followed by G-CSF alone 10 microg/kg/day for 2-3 days. The harvested CD34(+) cell count (P < 0.05) was statistically higher in group 3 than in group 1 or 2. Pre-collection WBC count in donors (P < 0.05), harvested MNC (P < 0.05) and CD3(+) cell count (P < 0.05) of group 2 or 3 were significantly higher than those of group 1. Recipients who received stem cells mobilized with combination regimens showed an earlier recovery of WBC and platelets count than those with GM-CSF alone. The incidence of acute graft-versus-host disease was not statistically different among three recipient groups. GM-CSF-based mobilization was well tolerated in normal healthy donors. The sequential combination regimen appears to be an excellent mobilization strategy and might be preferred as the optimal method in some clinical situations that need a higher number of stem cells.

Adult↗

D609-sensitive tyrosine phosphorylation is involved in Fas-mediated phospholipase D activation.

Both Fas and PMA can activate phospholipase D via activation of protein kinase Cbeta in A20 cells. Phospholipase D activity was increased 4 fold in the presence of Fas and 2.5 fold in the presence of PMA. The possible involvement of tyrosine phosphorylation in Fas-induced activation of phospholipase D was investigated. In five minute after Fas cross-linking, there was a prominent increase in tyrosine phosphorylated proteins, and it was completely inhibited by D609, a specific inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC). A tyrosine kinase inhibitor, genistein, can partially inhibit Fas-induced phospholipase D activation. There were no effects of genistein on Fas-induced activation of PC-PLC and protein kinase C. These results strongly indicate that tyrosine phosphorylation may in part account for the increase in phospholipase D activity by Fas cross-linking and D609 can block not only PC-PLC activity but also tyrosine phosphorylation involved in Fas-induced phospholipase D activation.

Animals↗

Biomechanical evaluation of diagonal fixation in pedicle screw instrumentation.

STUDY DESIGN: Flexibility tests and finite element analyses were performed for the biomechanical evaluation of diagonal transfixation in pedicle screw instrumentation. OBJECTIVE: To assess the biomechanical advantages of diagonal transfixation compared with conventional horizontal transfixation. SUMMARY AND BACKGROUND DATA: A few pedicle screw instrumentation systems allow the use of cross-links in the diagonal direction. Such a diagonal transfixation is anticipated to improve the surgical construct stability, but its biomechanical qualities have not been completely evaluated. METHODS: Flexibility tests were performed on 10 calf lumbar spines (L2-L5). Specimens were subjected to pure moments up to 8.2 Nm in flexion, extension, lateral bending, and extension while the resulting movements of L3 and L4 were measured by a three-dimensional motion analysis system. The tested cases included (1) intact, (2) pedicle screw fixation without transfixation after total removal of the L3-L4 disc, (3) pedicle screw fixation with diagonal transfixation, and (4) pedicle screw fixation with horizontal transfixation. Three-dimensional finite element models of the tested surgical constructs were also developed by use of three-dimensional beam elements to investigate the effect of diagonal transfixation and horizontal transfixation on the construct stability and the corresponding stress changes in the screws. RESULTS: When compared with no transfixation, horizontal transfixation significantly improved the lateral bending and axial rotation stability by 15.7% and 13.9%, respectively, but there was no improvement of stability in flexion and extension. By contrast, diagonal transfixation significantly improved the flexion and extension stability by 12% and 10.7%, respectively, but not the lateral bending and axial rotation stability in comparison with no transfixation. Comparison between horizontal transfixation and diagonal transfixation showed that the stabilizing effect of diagonal transfixation was greater in flexion and extension (13% and 11%, P < 0.01) than that of horizontal transfixation but smaller in lateral bending (11%, P < 0.05) and axial rotation (6.6%, P > 0.1). Finite element model predictions of the motion changes were similar to the changes observed in flexibility tests. In horizontal transfixation, the load changes, compared with no transfixion, were a 0.02% increase in flexion-extension, a 27.5% increase in lateral bending, and a 58% decrease in axial rotation, and the magnitudes of the moments applied on both the right and left pedicle screws were identical. However, when diagonal transfixation was achieved by connecting the left superior screw and the right inferior screw, the loads in the left screw were increased by 11.5% in flexion-extension, 43.6% in lateral bending, and 7.9% in axial rotation, whereas the loads in the right screw were decreased by 10.9% in flexion-extension, increased by 0.06% in lateral bending, and decreased by 18.1% in axial rotation. CONCLUSIONS: The results of this study showed that diagonal transfixation provides more rigid fixation in flexion and extension but less in lateral bending and axial rotation in comparison with horizontal transfixation. Furthermore, greater stresses in the pedicle screws were predicted in the diagonal transfixation model. These limitations of diagonal transfixation should be considered carefully for clinical application.

Animals↗

Synthesis of a tetrahomodioxacalix[4]arene tetraamide and the crystal structure of its lead ion complex.

The 1,4-alternate tetrahomodioxacalix[4]arene tetraamide 4 with four p-phenyl groups on its upper rim was synthesized. In two-phase metal picrate extraction, 4 exhibited Pb2+ selectivity with formation of a 1:1 complex in chloroform. In the solid-state structure of the 4*Pb(Pic)2 complex, Pb2+ is bound by the carbonyl oxygens of two adjacent amide groups and an aryl-alkyl ether oxygen atom of one of these amide-containing substituents. The crystal structure and 1H NMR spectrum of the 4*Pb2+ complex reveals pi-metal ion complexation of one aromatic ring in the ligand with Pb2+.

Journal Article↗

Altered expression of the fragile histidine triad gene in primary gastric adenocarcinomas.

Genomic alterations and abnormal expression of the fragile histidine triad (FHIT) gene in gastric carcinomas were examined to determine whether the FHIT gene is actually a frequent target for alteration during gastric carcinogenesis. To correlate DNA and RNA lesions of the FHIT gene with the effect on FHIT protein expression, we have investigated the FHIT gene for loss of heterozygosity (LOH), aberrant transcripts, point mutations, and protein expression in 35 gastric adenocarcinomas. Allelic loss at D3S1300 was detected in 7 of 33 (21%) informative cases. Aberrant transcripts, with deletions and/or insertions, were observed in 20 of 35 (57.1%) cases and resulted from alternative splicing through exon skipping and/or insertion of the FHIT intron 5 sequence or activation of the cryptic splice site. Point mutations were not found in the FHIT coding region but detected in noncoding exon 2, 3, 4, or 5 of eight aberrant transcripts. Significant reduction of FHIT protein expression was observed in 22 of 35 (62.9%) cases. Aberrant FHIT transcription was shown to be associated with loss of FHIT protein expression. However, aberrant FHIT transcripts themselves were not associated with any clinicopathological parameters, such as age, sex, tumor site, or clinical stage. Moreover, there was no association between the presence of LOH at D3S1300 and the expression of aberrant FHIT transcripts. Nevertheless, high frequency of aberrant FHIT transcripts, significant rate of LOH at D3S1300, and altered expression of the FHIT protein indicate that alterations of the FHIT gene can play an important role in gastric carcinogenesis.

Acid Anhydride Hydrolases↗

Effect of endplate conditions and bone mineral density on the compressive strength of the graft-endplate interface in anterior cervical spine fusion.

STUDY DESIGN: Destructive compression tests and finite element analyses were conducted to investigate the biomechanical strength at the graft-endplate interface in anterior cervical fusion. OBJECTIVES: To investigate the effect of endplate thickness, endplate holes, and bone mineral density of the vertebral body on the biomechanical strength of the endplate-graft interface in an anterior interbody fusion of the cervical spine. SUMMARY OF BACKGROUND: Subsidence of the graft into the vertebral body is a well-known complication in anterior cervical fusion. However, there is no information in the literature regarding the compressive strength of the graft-endplate interface in relation to the endplate thickness, holes in the endplate, and bone mineral density of the vertebral body. METHODS: Biomechanical destructive compression tests and finite element analyses were performed in this study. Cervical vertebral bodies (C3-C7) isolated from seven cadaveric cervical spines (age at death 69-86 years, mean 79 years) were used for compression tests. Bone mineral density of each vertebral body was measured using a dual energy radiograph absorptiometry unit. Endplate thickness was measured using three coronal computed tomography images of the middle portion of the vertebral body obtained using a computer-assisted imaging analysis. Then each vertebral body was cut into halves through the horizontal plane. A total of 54 specimens, consisting of one endplate and half of the vertebral body, were obtained after excluding eight vertebrae with gross pathology on plain radiograph. Specimens were assigned to one of three groups with different endplate conditions (Group I, intact; Group II, partial removal; and Group III, complete removal) so that group mean bone mineral density became similar. Each endplate was slowly compressed until failure using an 8-mm-diameter metal indenter, and the load to failure was determined as a maximum force on a recorded force-displacement curve. The effect on the strength of the graft-endplate interface of various hole patterns in the endplate was studied using a finite element technique. The simulatedhole patterns included the following: one large central hole, two lateral holes, two holes in the anterior and posterior portion of the endplate, and four holes evenly distributed from the center of the endplate. Stress distribution in the endplate was predicted in response to an axial compressive force of 110 N, and the elements with von Mises stress greater than 4.0 MPa were determined as failed. RESULTS: The endplate thickness and bone mineral density were similar at all cervical levels, and the superior and inferior endplates had similar thickness at all cervical levels. There was no significant association between bone mineral density and endplate thickness. Load to failure was found to have a significant association with bone mineral density but not with endplate thickness. However, load to failure tends to decrease with incremental removal of the endplate, and load to failure of the specimens with an intact endplate was significantly greater than that of the specimens with no endplate. Finite element model predictions showed significant influence of the hole pattern on the fraction of the upper endplate exposed to fracture stress. A large hole was predicted to be more effective than the other patterns at distributing a compressive load across the remaining area and thus minimizing the potential fracture area. CONCLUSION: Results of this study suggest that it is important to preserve the endplate as much as possible to prevent graft subsidence into the vertebral body, particularly in patients with poor bone quality. It is preferable to make one central hole rather than multiple smaller holes in the endplate for vascularity of the bone graft because it reduces the surface area exposed to fracture stresses.

Aged↗

Interferon alpha /beta promotes cell survival by activating nuclear factor kappa B through phosphatidylinositol 3-kinase and Akt.

Interferons (IFNs) play critical roles in host defense by modulating gene expression via activation of signal transducer and activator of transcription (STAT) factors. IFN-alpha/beta also activates another transcription factor, nuclear factor kappaB (NF-kappaB), which protects cells against apoptotic stimuli. NF-kappaB activation requires the IFN-dependent association of STAT3 with the IFNAR1 chain of the IFN receptor. IFN-dependent NF-kappaB activation involves the sequential activation of a serine kinase cascade involving phosphatidylinositol 3-kinase (PI-3K) and Akt. Whereas constitutively active PI-3K and Akt induce NF-kappaB activation, Ly294002 (a PI-3K inhibitor), dominant-negative PI-3K, and kinase-dead Akt block IFN-dependent NF-kappaB activation. Moreover, dominant-negative PI-3K blocks IFN-promoted degradation of kappaBox alpha. Ly294002, a dominant-negative PI-3K construct, and kinase-dead Akt block IFN-promoted cell survival, enhancing apoptotic cell death. Therefore, STAT3, PI-3K, and Akt are components of an IFN signaling pathway that promotes cell survival through NF-kappaB activation.

Apoptosis↗

Extracranial radiosurgery: immobilizing liver motion in dogs using high-frequency jet ventilation and total intravenous anesthesia.

PURPOSE: Extracranial radiosurgery requires control of organ motion. The purpose of this study is to quantitatively determine the extent of liver motion in anesthetized dogs with continuous i.v. propofol infusion with or without muscle relaxants and high-frequency jet ventilation. METHODS AND MATERIALS: Five dogs were used in the experiment. Each dog was restrained while anesthetized in the supine position using an alpha cradle. Surgical metal clips were implanted around the liver periphery so that its motion could be visualized using a fluoroscopic imaging device in a conventional simulator. Initially, two orthogonal simulation films were taken to correlate locations of implanted clips. Two orthogonal views of fluoroscopic images for each anesthetized dog were recorded on a magnetic tape and analyzed from the post-imaging data. Liver motion was documented under the following three conditions: 1) ventilated with a conventional mechanical ventilator, 2) ventilated with a high-frequency jet ventilator, and 3) ventilated with a high-frequency jet ventilator and total muscle paralysis (with vecuronium injection). The maximum liver motion for each dog was analyzed in three orthogonal directions: the inferior-to-superior direction, the anterior-to-posterior direction, and the right-to-left direction. RESULTS: When the anesthetized dogs were ventilated with a conventional mechanical ventilator, the average liver motions were 1.2 cm in the inferior-to-superior direction, 0.4 cm in the anterior-to-posterior direction, and 0.2 cm in the right-to-left direction, respectively. After the introduction of high-frequency jet ventilation, the average liver motions were reduced to 0.2 cm in the inferior-to-superior direction, 0.2 cm in the anterior-to-posterior direction, and 0.1 cm in the right-to-left direction. The maximum liver motion was dependent on ventilator settings. There was no additional measurable motion reduction with the addition of the muscle relaxant. CONCLUSION: The liver motion in each anesthetized dog was controlled under 3.0 mm in all directions with the use of high-frequency jet ventilation. No detectable advantage was identified by the injection of muscle relaxant in terms of further reducing the liver motion. The preclinical animal study indicated that the use of high-frequency jet ventilation (HFJV) would be able to limit the liver motion to an extent acceptable for the application of extracranial radiosurgery in humans. Radiosurgery for localized liver tumors warrants further investigation.

Anesthesia, Intravenous↗

Correlation of hematopoietic progenitor cell count determined by the SE-automated hematology analyzer with CD34(+) cell count by flow cytometry in leukapheresis products.

The yield of stem cell collection after mobilization is crucial for autologous peripheral blood stem cell (PBSC) transplantation. Quantitative determinations of CD34(+) cells using flow cytometry or stem cell culture have been used, but these methods require much time, technical experience, and expensive reagents. The automated hematology analyzer (Sysmex SE-9000trade mark, TOA, Japan) equipped with the Immature Information (IMI) channel for immature myeloid cells can detect IMI(+) cells within 90 sec. Detection is made possible by the combination of a special reagent system and direct current/radiofrequency biosensors. We studied the relation of IMI(+) cells and variable cell counts with CD34(+) cell yield in autologous stem cell harvest. In a series of 32 patients (median age, 44 years; M:F = 11:21), 184 leukaphereses were performed after mobilization regimens with chemotherapy and G-CSF or G-CSF alone. Full blood cell counts were enumerated on peripheral blood (PB) samples taken prior to each leukapheresis. Mononuclear cell (MNC) and IMI(+) cell counts by automated hematology analyzer and flow cytometry based CD34(+) cell yield were measured on the harvested product. The relationship among PB white blood cells (WBC), PB monocytes, IMI(+) cells, MNC, and CD34(+) cell yield in a single leukapheresis was estimated by Pearson correlation analysis. PB WBC count showed no correlation with CD34(+) cell yield in a single leukapheresis (r = 0.02, P = 0.81). PB monocyte count showed a weak correlation (r = 0.21, P = 0.01) and MNC in harvest also showed a weak correlation (r = 0.36, P = 0.0001) with CD34(+) cell yield. In contrast, CD34(+) cell yield correlated well with IMI(+) cell count (r = 0.68, P = 0.0001), and data could be fitted by a linear regression equation, y = 0.330 + 0.974x. IMI(+) cell assay by the automated hematology analyzer correlated well with the CD34(+) cell yield in a mobilized autologous stem cell harvest. The IMI(+) cell count might be used as a simple and efficient indicator of blood stem cell mobilization and collection.

Adolescent↗

Fumigant toxicity of volatile natural products from Korean spices and medicinal plants towards the rice weevil, Sitophilus oryzae (L).

The fumigant toxicity of various volatile constituents of essential oils extracted from sixteen Korean spices and medicinal plants towards the rice weevil, Sitophilus oryzae L (Coleoptera: Curculionidae), was determined. The most potent toxicity was found in the essential oil from Mentha arvensis L. var piperascens (LC50 = 45.5 microliters litre-1 air). GC-MS analysis of essential oil from M arvensis showed it to be rich in menthol (63.2%), menthone (13.1%) and limonene (1.5%), followed in abundance by beta-pinene (0.7%), alpha-pinene (0.6%) and linalool (0.2%). Treatment of S oryzae with each of these terpenes showed menthone to be most active (LC50 = 12.7 microliters litre-1 air) followed by linalool (LC50 = 39.2 microliters litre-1 air) and alpha-pinene (LC50 = 54.9 microliters litre-1 air). Studies on inhibition of acetylcholinesterase activity of S oryzae showed menthone to have a nine-fold lower inhibitory effect than menthol, despite menthone being 8.1-fold more toxic than menthol to the rice weevil. Different modes of toxicity of these monoterpenes towards S oryzae are discussed.

Acetylcholinesterase↗

Histamine release induced by dendroaspis natriuretic peptide from rat mast cells.

Dendroaspis natriuretic peptide (DNP), recently isolated from the venom of the green Mamba snake Dendroaspis angusticeps, is a 38 amino acid peptide containing a 17 amino acid disulfide ring structure similar to that of the natriuretic peptide family. The natriuretic peptide family is known to induce histamine release from human and rat mast cells, but there are no published data concerning the effects of DNP on histamine release from mast cells. The purpose of this study is to investigate whether DNP induces the histamine release from rat peritoneal mast cells (RMPCs) and to determine the mechanism of DNP-induced histamine release from RPMCs. After treatment of RPMC with DNP, mast cell degranulation was observed, and calcium uptake and histamine release were measured. DNP released the histamine, induced the mast cell degranulation, and increased the calcium uptake of RPMCs, in a dose-dependent manner. The results indicate that DNP can increase Ca-uptake and induce histamine release.

Animals↗

Characterization of uterine epidermal growth factor during early pregnancy in pigs.

Genomic research has identified a quantitative trait locus for uterine capacity, a component trait contributing to litter size, on porcine chromosome 8. The epidermal growth factor (EGF) gene, on porcine chromosome 8, may influence uterine capacity because of its growth-promoting activities. Using reverse transcription-polymerase chain reaction (PCR) and iterative screening of a porcine reproductive tissue cDNA library, 4932 bp cDNA sequence coding for porcine EGF precursor was obtained. The predicted protein sequence of the EGF precursor contained 1214 amino acids, similar to human EGF precursor (1207 amino acids, 81% identity). Curiously, the sequence of the mature peptide was less homologous between species than other regions of EGF precursor. The presence of conserved regions outside the mature peptide may suggest that these regions are functionally important. Expression of EGF mRNA in the endometrium of White crossbred gilts (n = 3 to 5 each) was determined by Northern blotting using 20 microg of total RNA from endometrium of D 10, 13, and 15 cyclic, and D 10, 13, 15, 20, 30, and 40 of pregnant gilts. A 3342 bp probe from EGF precursor was used. The bands corresponding to EGF mRNA were quantified by densitometry and results were analyzed by ANOVA. EGF mRNA expression decreased significantly from D 13 to 15 of the cycle and pregnancy (P = 0.04), and from D 30 to 40 of pregnancy (P = 0.01). These findings show that EGF mRNA expression is temporally regulated during the cycle and early pregnancy, and this pattern of gene expression may be important during early conceptus development.

3' Untranslated Regions↗

Low-density lipoprotein-antioxidant constituents of Saururus chinensis.

A new diarylbutane lignan, saururin A (1), and a known 8-O-4'-type neolignan, machilin D (2), were isolated from a total methanol extract of the underground parts of Saururus chinensis. The structures of 1 and 2 were elucidated by spectroscopic data analysis. Compounds 1, 2, and virolin (3) (the methyl ether of 2) exhibited significant low-density lipoprotein (LDL)-antioxidant activity in the thiobarbituric acid-reactive substance (TBARS) assay with IC(50) values of 8.5, 2.9, and 4.3 microM, respectively.

Anti-Inflammatory Agents, Non-Steroidal↗

Alternative embryo transfer on day 3 or day 5 for reducing the risk of multiple gestations.

PURPOSE: This study was carried out to reduce the possibility of high-order multiple gestations and the failure of embryo transfer by determining their replacement date based on the number and quality of 2-day embryos. METHODS: All zygotes were cocultured with cumulus cells in 10 microliters of YS medium containing 10% human follicular fluid (hFF) for 48 or 96 hr. In period I, all embryos were transferred on day 3 (1032 cycles). In period II, the embryos were transferred on either day 3 or day 5 by determining their replacement date based on the number and quality of 2-day embryos: there were 2701 patients in whom embryos were replaced on day 3 (in the case that the number of zygotes was less than eight and the number of good-quality embryos was less than three) and 1952 patients less than 40 years old in whom embryos were replaced on day 5 (in the case that the number of zygotes was eight or more and/or the number of good-quality embryos was three or more). On the other hand, patients who were 40 years old or more were alloted to day 3 transfer cycles, regardless of the number and quality of the 2-day embryos, due to the possibility of their not producing blastocyst-stage embryos in vitro. RESULTS: The number of embryos transferred in period II was 2.9 +/- 0.6, while that in period I was 3.7 +/- 0.5. The multiple pregnancy rate was significantly decreased in period II (30.7%) compared to that (49.6%) in period I, while the pregnancy and implantation rates in period II (36.1 and 16.4%, respectively) were not lower than those (34.9 and 16.1%, respectively) in period I. The rate of triplet or more gestations was significantly minimized in period II (2.3%) compared to that in period I (26.5%). CONCLUSIONS: We propose that determination of the date on which embryos should be transferred based on the number and quality of embryos on day 2 may help to maintain an acceptable pregnancy rate, while minimizing embryo transfer failure and high-order multiple gestations.

Adult↗