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Biomedical subjects

K J Kim

Publications and source records attributed to K J Kim.

At least 37 records · Page 2Linked to original sources
PubMed2001

Exponential gain and saturation of a self-amplified spontaneous emission free-electron laser.

Self-amplified spontaneous emission in a free-electron laser has been proposed for the generation of very high brightness coherent x-rays. This process involves passing a high-energy, high-charge, short-pulse, low-energy-spread, and low-emittance electron beam through the periodic magnetic field of a long series of high-quality undulator magnets. The radiation produced grows exponentially in intensity until it reaches a saturation point. We report on the demonstration of self-amplified spontaneous emission gain, exponential growth, and saturation at visible (530 nanometers) and ultraviolet (385 nanometers) wavelengths. Good agreement between theory and simulation indicates that scaling to much shorter wavelengths may be possible. These results confirm the physics behind the self-amplified spontaneous emission process and forward the development of an operational x-ray free-electron laser.

Journal Article↗
PubMed2001

Vitreoscilla hemoglobin. Intracellular localization and binding to membranes.

The obligate aerobic bacterium, Vitreoscilla, synthesizes elevated quantities of a homodimeric hemoglobin (VHb) under hypoxic growth conditions. Expression of VHb in heterologous hosts often enhances growth and product formation. A role in facilitating oxygen transfer to the respiratory membranes is one explanation of its cellular function. Immunogold labeling of VHb in both Vitreoscilla and recombinant Escherichia coli bearing the VHb gene clearly indicated that VHb has a cytoplasmic (not periplasmic) localization and is concentrated near the periphery of the cytosolic face of the cell membrane. OmpA signal-peptide VHb fusions were transported into the periplasm in E. coli, but this did not confer any additional growth advantage. The interaction of VHb with respiratory membranes was also studied. The K(d) values for the binding of VHb to Vitreoscilla and E. coli cell membranes were approximately 5-6 microm, a 4-8-fold higher affinity than those of horse myoglobin and hemoglobin for these same membranes. VHb stimulated the ubiquinol-1 oxidase activity of inverted Vitreoscilla membranes by 68%. The inclusion of Vitreoscilla cytochrome bo in proteoliposomes led to 2.4- and 6-fold increases in VHb binding affinity and binding site number, respectively, relative to control liposomes, suggesting a direct interaction between VHb and cytochrome bo.

Animals↗
PubMed2001

Capsid size determination in the P2-P4 bacteriophage system: suppression of sir mutations in P2's capsid gene N by supersid mutations in P4's external scaffold gene sid.

The sid gene of the P2-dependent phage P4 provides an external scaffold so P2 N gene encoded protomers assemble as T = 4 capsids rather than as P2's T = 7 capsids. Mutations (sir) in the middle of N interfere with Sid's function. We describe a new P4 mutant class, nms ("supersid") mutations, which direct also P2 sir to provide small capsids. Three different nms mutations were located near the sid end, commingled with sid(-) mutations. Suppression of sir by nms is not allele-specific. Our results favor this interpretation of capsid size control: (i) sir mutations reduce pN protomer flexibility and thereby interfere with the generation of T = 4 compatible hexons; (ii) the C-termini of Sid molecules link up when forming the scaffold; nms mutations strengthen these Sid-Sid contacts and thus allow the scaffold to force even sir-type protomers to form T = 4 compatible hexons. Some related findings concern suppression of N ts mutations by P4.

Bacteriophage P2↗
PubMed2001

Recursive solution for beam dynamics of periodic focusing channels.

We present recursive analysis for beam dynamics of periodic focusing channels based on the Fourier coefficients of the focusing function. Formulas for orbit stability and the envelope function are derived. The results should be useful for numerical calculation and for developing analytical understanding of channels employing extended focusing elements. Applications to muon ionization cooling channels are discussed.

Journal Article↗
PubMed2001

Isotype-dependent inhibition of tumor growth in vivo by monoclonal antibodies to death receptor 4.

To explore an approach for death receptor targeting in cancer, we developed murine mAbs to human death receptor 4 (DR4). The mAb 4H6 (IgG1) competed with Apo2L/TNF-related apoptosis-inducing ligand (DR4's ligand) for binding to DR4, whereas mAb 4G7 (IgG2a) did not. In vitro, both mAbs showed minimal intrinsic apoptosis-inducing activity, but each triggered potent apoptosis upon cross-linking. In a colon tumor nude mouse model in vivo, mAb 4H6 treatment without addition of exogenous linkers induced apoptosis in tumor cells and caused complete tumor regression, whereas mAb 4G7 partially inhibited tumor growth. An IgG2a isotype switch variant of mAb 4H6 was much less effective in vivo than the parent IgG1-4H6, despite similar binding affinities to DR4. The same conclusion was obtained by comparing other IgG1 and IgG2 mAbs to DR4 for their anti-tumor activities in vivo. Thus, the isotype of anti-DR4 mAb may be more important than DR4 binding affinity for tumor elimination in vivo. Anti-DR4 mAbs of the IgG1 isotype may provide a useful tool for investigating the therapeutic potential of death receptor targeting in cancer.

Animals↗
PubMed2001

Palladium(0)-catalyzed carbonylation-coupling-cyclization of allenic sulfonamides with aryl iodides and carbon monoxide.

[reaction: see text] alpha-Allenic sulfonamides undergo carbonylation-coupling-endo-cyclization with aryl iodides in the presence of Pd(PPh(3))(4) (5 mol %), K(2)CO(3), and CO (20 atm) to form 3-aroyl-2- or 3-pyrrolines. Alternatively the carbonylation-coupling-exo-cyclization of gamma- and delta-substituted sulfonamides under the same conditions afforded pyrrolidine- or piperidine-substituted enones.

Journal Article↗
PubMed2001

Temporal contrast adaptation in the input and output signals of salamander retinal ganglion cells.

We investigated how the light-evoked input and output signals of salamander retinal ganglion cells adapt to changes in temporal contrast, i.e., changes in the depth of the temporal fluctuations in the light intensity about the mean. Increasing the temporal contrast sped the kinetics and reduced the sensitivity of both the light-evoked input currents measured at the ganglion cell soma and the output spike trains of the cell. The decline in sensitivity of the input currents after an increase in contrast had two distinct kinetic components with fast (<2 sec) and slow (>10 sec) time constants. The recovery of sensitivity after a decrease in contrast was dominated by a single component with an intermediate (4-18 sec) time constant. Contrast adaptation differed for on and off cells, with both the kinetics and amplitude of the light-evoked currents of off cells adapting more strongly than those of on cells. Contrast adaptation in the input currents of a ganglion cell, however, was unable to account for the extent of adaptation in the output spike trains of the cell, indicating that mechanisms intrinsic to the ganglion cell contributed. Indeed, when fluctuating currents were injected into a ganglion cell, the sensitivity of spike generation decreased with increased current variance. Pharmacological experiments indicated that adaptation of spike generation to the current variance was attributable to properties of tetrodotoxin-sensitive Na(+) channels.

Action Potentials↗
PubMed2001

Activated human T cells directly induce osteoclastogenesis from human monocytes: possible role of T cells in bone destruction in rheumatoid arthritis patients.

OBJECTIVE: To elucidate the direct role of human T cells in the induction of osteoclastogenesis in rheumatoid arthritis (RA), by studying human monocytes and the pathogenetic roles of receptor activator of nuclear factor kappaB ligand (RANKL), RANK, and osteoprotegerin (OPG). METHODS: Synovial tissue obtained at total knee replacement was stained immunohistologically using anti-RANKL, CD3, and CD4 antibodies. Synovial fluid was obtained from patients with RA, osteoarthritis (OA), gout, or trauma. Concentrations of the soluble form of RANKL (sRANKL) and OPG in the synovial fluid were measured by enzyme-linked immunosorbent assay. Activated T cells from peripheral blood mononuclear cells (PBMC) of healthy volunteers were cultured with human monocytes from PBMC. RESULTS: Immunostaining of the synovial tissue of RA patients demonstrated that RANKL-positive cells were detected in a subset of fibroblast-like synoviocytes and infiltrating mononuclear cells. Double immunostaining revealed that RANKL-positive cells were detected in a subset of CD3+ cells and CD4+ cells. An increased concentration of sRANKL and a decreased concentration of OPG were detected in synovial fluid from RA patients. The ratio of the concentration of sRANKL to that of OPG was significantly higher in synovial fluid of RA patients than in synovial fluid of patients with OA or gout. The activated T cells expressing RANKL induced osteoclastogenesis from autologous peripheral monocytes. The role of RANKL in this osteoclastogenetic process was confirmed by dose-dependent inhibition by OPG. CONCLUSION: The present study is the first to demonstrate osteoclastogenesis using human-derived T cells and monocytes. In addition, the present findings suggest that excess production of RANKL by activated T cells increases the level of sRANKL in synovial fluid and may contribute to osteoclastic bone resorption in RA patients.

Antibodies↗
PubMed2001

Osteoprotegerin inhibits in vitro mouse osteoclast formation induced by joint fluid from failed total hip arthroplasty.

Osteoprotegerin (OPG) is a key regulator of osteoclastogenesis. We investigated the presence of OPG and bone-resorbing cytokines, the potential of osteoclastic differentiation in joint fluid from failed total hip arthroplasty (THA), and the inhibitory effect of OPG on osteoclast formation in vitro induced by the joint fluid. The study was aimed to clarify one important step in the cascade of periprosthetic osteolysis in the process of implant loosening. OPG levels in failed THA joint fluid of 20 cases were significantly lower than osteoarthritis (OA) joint fluid of 15 cases (p < 0.001). The levels of bone-resorbing cytokines, interleukin (IL)-1beta, and IL-6 were significantly higher in failed THA joint fluid than OA fluid (p < 0.001 and p = 0.001, respectively). Marked osteoclast formation was observed in the presence of failed THA joint fluid in the mouse coculture system, when compared to OA fluid (p < 0.001). The addition of 100 ng/mL OPG to the mouse coculture system completely inhibited osteoclast formation in the presence of failed THA joint fluid (p < 0.001). The data suggest that low levels of OPG combined with higher IL-1beta and IL-6 levels represent the potential of osteoclast differentiation and its activation in failed THA joint fluid. Inhibition of osteoclastogenesis in vitro by OPG suggests that a low level of OPG with elevated bone resorbing cytokines contributes to periprosthetic osteolysis via osteolytic joint fluid, thus leading to THA prosthesis loosening.

Animals↗
PubMed2001

Intractable epilepsy associated with brain tumors in children: surgical modality and outcome.

OBJECTS: The aim of this study was to evaluate the role of surgical modality in children with brain tumors and intractable epilepsy. METHODS: Twenty-three patients who were treated for brain tumors and intractable epilepsy between January 1985 and March 1998 were retrospectively reviewed. The most common tumors were dysembryoplastic neuroepithelial tumors (n=9), oligodendrogliomas (n=6), and gangliogliomas (n=5). Six patients exhibited cortical dysplasia. The mean duration of follow-up was 43.4 months (range 12 to 125 months). Seizure outcome was more favorable (Engel's classes I and II) in patients with a complete resection of tumor (14/14 vs 6/9 for incomplete resection; P<0.05). There was no significant difference in seizure outcome between lesionectomy (n=13) and epilepsy surgery (n=10). The likelihood of requiring postoperative antiepileptic drugs was not influenced by the extent of resection or type of surgery. CONCLUSIONS: On the basis of this study, we conclude that the complete resection of these tumors can be an appropriate initial treatment for children with brain tumors who experience intractable epilepsy.

Adolescent↗
PubMed2001

Stromal cell activity in bone marrow from the tibia and iliac crest of patients with rheumatoid arthritis.

Bone marrow aspirates were obtained from the iliac crest and tibial epiphysis in 23 patients with rheumatoid arthritis (RA) who were undergoing total knee arthroplasty. The number of fibroblast colony-forming units (CFU-F), which contain osteogenic precursor cells, and alkaline phosphatase (ALP) activity, as a marker of the osteoblastic phenotype. were compared between the iliac and tibial marrow for each patient. The prevalence of CFU-F in tibial marrow was similar to that in iliac marrow (96% vs 100%, respectively). However, the average number of CFU-F per 4 x 10(5) bone marrow mononuclear cells was significantly lower in tibial marrow than in iliac marrow (8.2 vs 28.1, respectively; P < 0.01). Although ALP activity was detected in all iliac and tibial marrow specimens, it was significantly lower in tibial marrow compared with iliac marrow (3.7 vs 11.9 nmol/min/mg protein, respectively; P < 0.01). In addition, there was a significant correlation between the patient's age and the number of CFU-F in iliac marrow (r = -0.547; P < 0.01), although there was no correlation in tibial marrow. These results demonstrate that the osteogenic activity of bone marrow varies at different sites in patients with RA. The data may also contribute to further investigation into the differential effects of various disease processes on systemic as well as local stromal cell activity in bone marrow.

Adult↗
PubMed2001

Analysis of microfiltration performance with constant flux processing of secondary effluent.

This study involves the microfiltration (MF) of secondary effluent from a sequencing batch reactor processing industrial waste. The MF unit was a hollow fibre module with gas backwash capability, and operated with pumped permeate (controlled flux) and dead-end, crossflow or intermittent feed. The results showed that crossflow had no effect on flux and that intermittent dead-end filtration was less productive than non-intermittent operation. For dead-end filtration the cycle-time between gas backwashes depends very significantly on the imposed flux (varying from about 100 min at 30 L/m2 h to about 5 min at 90 L, m2 h) and the feed solids content. Optimal operation has to balance operating (energy for backwash) costs and the capital (membrane area) costs. Cost analysis based on capital and energy costs indicates that for lower energy cost the unit needs to be operated at lower imposed flux but to minimise total cost it is necessary to operate the unit above 60 L/m2 h imposed flux depending on the maximum transmembrane pressure (TMP) allowed before back washing. Further analysis of TMP profiles showed that membrane resistance increased over time towards a maximum, which tended to increase with imposed flux. This implies more frequent chemical cleaning for high flux operation. Specific cake resistances were deduced from the profiles and indicated cake compression at higher flux and larger maximum TMP. Results of long-term trials are also reported. Water quality analysis shows consistent quality of permeate

Equipment Design↗
PubMed2001

Survival of conditionally immortalized hepatocytes in the spleen of syngeneic rats.

BACKGROUND: Hepatocyte transplantation has been shown to be effective in the treatment of liver failure; however, the shortage of donor organs limits its clinical application. Several reports have suggested that conditionally immortalized hepatocytes (CIH) could be an alternative to primary hepatocytes. However, CIH are known to undergo apoptosis in vitro at a non-permissive temperature, which is similar to body temperature. METHODS: To investigate the duration of survival and in vivo apoptosis of CIH in the syngeneic host, the L2A2 cells (a kind of CIH) that were established from hepatocytes of a Lewis rat with a gene for a temperature-sensitive Simian Virus 40 (SV40) large T antigen were transplanted into the spleen. Cells were isolated from the spleen that was removed periodically up to 6 months, and used to detect the presence of the L2A2 cells among them with the selective culture for CIH and T-antigen PCR. In situ apoptosis of L2A2 cells was also examined. In order to improve the survival of transplanted L2A2 cells in the host, a group of rats were partially hepatectomized 1 day before transplantation was performed. RESULTS: The L2A2 cells secreted albumin at a rate of 1.17 +/- 0.18 microg/24 h per 10(6) cells in vitro. After transplantation, L2A2 cell colonies and PCR amplification bands appeared up to 14 and 7 days, respectively, but this duration was not prolonged by a partial hepatectomy. The spleen showed a large number of hepatocytes that were in the process of dying on the 5th day, and only a number of ghost hepatocytes were present on the 7th day of transplantation. No tumors were found during the 6-month observation period. CONCLUSIONS: Conditionally immortalized hepatocytes can survive in the spleen for a limited period, in spite of the growth stimulation, most likely because they undergo apoptosis in vivo as well as in vitro at a non-permissive temperature. These data suggest that the use of these cells in hepatocyte transplantation be limited to temporary hepatic support.

Albumins↗
PubMed2001

Hemifacial seizure of cerebellar ganglioglioma origin: seizure control by tumor resection.

The cerebellum is known to have an inhibitory effect on seizures. Nevertheless, cerebellar dysplastic lesions can be epileptogenic. A 4-month-old infant had paroxysmal facial contractions; tachypnea and nystagmoid eyeball and tremulous movements were occasionally combined. These evolved to stereotypic clinical patterns and frequencies, which increased despite administration of antiepileptic drugs (AEDs). Magnetic resonance imaging (MRI) demonstrated a mass arising from the superior cerebellar peduncle, although video-scalp EEG monitoring revealed no abnormal findings. Positron emission tomography with [(18)F]fluorodeoxyglucose revealed focal hypermetabolism in the same area identified by MRI. A depth electrode implanted in the mass revealed focal spike-and-wave discharges. The lesion was partly removed; pathologic diagnosis was ganglioglioma. Because of incomplete seizure control and residual tumor visible on MRI, a second operation was performed. After complete excision of the tumor, the patient became seizure free without AEDs. This case confirms the presence of seizure originating from the cerebellum and emphasizes the need for the complete removal of an epileptogenic lesion.

Cerebellar Neoplasms↗
PubMed2001

Lung fibrosis in Sprague-Dawley rats, induced by exposure to manual metal arc-stainless steel welding fumes.

To investigate the disease process of pneumoconiosis induced by welding-fume exposure, a lung fibrosis model was established by building a stainless steel arc welding fume generation system and exposing male Sprague-Dawley rats for 90 days. The rats were exposed to welding fumes with concentrations of 57-67 mg/m3 (low dose) and 105-118 mg/m3 (high dose) total suspended particulates for 2 h per day in an inhalation chamber for 90 days. The concentrations of the main metals, Fe, Mn, Cr, and Ni, were measured in the welding fumes, plus the gaseous compounds, including nitrous gases and ozone, were monitored. During the exposure period, the animals were sacrificed after the initial 2-h exposure and after 15, 30, 60, and 90 days. Histopathological examinations were conducted on the animals' upper respiratory tract, including the nasal pathway and conducting airway, plus the gas exchange region, including the alveolar ducts, alveolar sacs, and alveoli. When compared to the control group, the lung weights did not increase significantly in the low-dose group, yet in the high-dose group there was a significant increase from day 15 to day 90. The histopathological examination combined with fibrosis-specific staining (Masson's trichrome) indicated that the lungs in the low-dose group did not exhibit any progressive fibrotic changes. Whereas, the lungs in the high-dose group exhibited early delicate fibrosis from day 15, which progressed into the perivascular and peribronchiolar regions by day 30. Interstitial fibrosis appeared at day 60 and became prominent by day 90, along with the additional appearance of pleural fibrosis. Accordingly, it would appear that a significant dose of welding-fume exposure was required to induce lung fibrosis.

Administration, Inhalation↗