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Biomedical subjects

C Kim

Publications and source records attributed to C Kim.

At least 55 records · Page 3Linked to original sources

Improvement of insulin sensitivity by chelation of intracellular Ca(2+) in high-fat-fed rats.

It has been postulated that sustained high levels of intracellular calcium concentration ([Ca(2+)](i)) in the insulin target cells may cause insulin resistance. We evaluated this hypothesis by examining the effect of an intracellular Ca(2+) chelator, 5,5'-dimethyl derivative of bis (o-aminophenoxy) ethane-N,N,N',N' tetraacetic acetoxymethyl ester (dimethyl-BAPTA/AM), on insulin resistance. Insulin resistance was induced in rats by feeding a high-fat diet for 3 to 4 weeks. The whole body insulin sensitivity was determined by the steady state glucose infusion rate (GIR) under euglycemic hyperinsulinemic (6 mU x kg(-1) x min(-1)) clamps. Compared with control rats, the high-fat diet (HFD) fed rats showed significantly lower GIR (12.2 +/- 0.7 v 20.2 +/- 0.9 mg x kg(-1) x min(-1); P <.01). In the HFD rats, an intravenous injection of dimethyl-BAPTA/AM (6 mg/kg) 90 minutes before the clamps significantly increased GIR to 16.3 +/- 0.9 mg x kg(-1) x min(-1) (P <.02), reversing insulin resistance by about 50%; but this intervention had no effect in the controls. This increase in GIR by dimethyl-BAPTA/AM was observed without an increase in femoral artery blood flow, indicating that the chelator increased GIR directly through improving cellular responsiveness to insulin. The stimulatory effect of insulin on 2-deoxy glucose (2-DG) uptake by the isolated epididymal adipocytes was reduced by 35% in the HFD rats compared with the control rats (P <.01). Pretreatment of the HFD rats with dimethyl-BAPTA/AM restored 2-DG uptake to the level in the control rats. The direct measurement of [Ca(2+)](i) using fura-2/AM in isolated adipocytes showed that basal [Ca(2+)](i) was significantly higher in the HFD rats than in the control rats (145 +/- 11 v 112 +/- 9 nmol/L; P <.05). An injection of dimethyl-BAPTA/AM in the HFD rats lowered [Ca(2+)](i) to 127 +/- 11 nmol/L, which did not differ from the level in the control rats (P >.2). The present study clearly demonstrates that an injection of intracellular Ca(2+) chelator in the HFD rats reverses insulin resistance, as well as normalizes elevated [Ca(2+)](i) in the insulin target cells. The results strongly support that sustained high levels of [Ca(2+)](i) in the insulin target cells may play an important role in insulin resistance, at least in the HFD rats.

Adipocytes↗

Usefulness of silicone plate for sellar floor reconstruction.

During the transsphenoidal approach (TSA), the proper sellar floor reconstruction plays an important role in the surgical results. The authors have evaluated the usefulness of a silicone as a substitute for bone splint in sellar floor reconstruction. Silicone plates were used in 10 patients who had 7 pituitary adenomas, 2 Rathke's cleft cysts, and 1 metastatic tumor. Among the ten cases, seven underwent standard TSAs and three received extended TSAs. The silicone plate was cut to a size slightly larger than that of bone window, inserted with a three-pronged fork, and then adjusted precisely. In nine patients, complications that related to surgical repair did not occur. A postoperative cerebrospinal fluid (CSF) rhinorrhea occurred in one pituitary macroadenoma, and no infection was observed in any case. From the authors' experience, advantages of the silicone plate are its simplicity to shape for any size of defects, and the easy detectability of the previous bone window at reoperation.

Adult↗

Effect of sustained contraction on motor unit action potentials and EMG power spectrum of human masticatory muscles.

The sequelae of a sustained clench are incompletely understood. Our experimental questions were to compare the responses of men and women, to compare masseter and anterior temporalis muscles, and to test hypotheses for the reduction of the median frequency of power spectra. We recorded duration, amplitude, number of phases, and area of the motor unit action potential before and after a sustained clench and the median frequency of the electromyographic power spectrum in 41 subjects. After the clench, the median frequency was lower, the action potential duration longer, the number of phases increased, and the area larger, but the amplitude was not different. Males and females failed to differ. Compared with the temporalis, the masseter had a lower median frequency, longer duration, larger number of phases, and increased area. Our results are consistent with a decrease in the conduction velocity of the muscle action potential as an explanation of the spectral shift.

Action Potentials↗

Evaluation of several respirometry-based activated sludge toxicity control strategies.

Four different strategies including influent storage and reintroduction, step-feeding, rapid sludge recycle and waste sludge storage were evaluated using the denitrification layout of the IWA simulation benchmark. The control objective was to minimise deterioration in effluent quality caused by a certain toxic input event. In these strategies the maximum specific respiration rate (Rmax) was selected as a measured and controlled variable. To simplify the analysis, the toxicant was assumed to be a soluble and nonbiodegradable substance. Two toxic influent files were developed with square-wave input lasting 3 hours. To detect the influent toxicity, a pseudo-online flow-through respirometer was applied. A number of simulations were performed and the results suggested that the influent storage and reintroduction strategy provided the most optimistic results and other strategies could not mitigate the toxic effect. The influent storage and reintroduction strategy strongly depended on reintroduction flow rate from the storage tank. The simulation according to reintroduction flow could estimate the time required for completely treating toxic wastewater stored in the storage tank. Also the IWA simulation benchmark was enhanced to evaluate toxicity effect on the activated sludge process.

Benchmarking↗

Genetic algorithms for the application of Activated Sludge Model No. 1.

The genetic algorithm (GA) has been integrated into the IWA ASM No. 1 to calibrate important stoichiometric and kinetic parameters. The evolutionary feature of GA was used to configure the multiple local optima as well as the global optimum. The objective function of optimization was designed to minimize the difference between estimated and measured effluent concentrations at the activated sludge system. Both steady state and dynamic data of the simulation benchmark were used for calibration using denitrification layout. Depending upon the confidence intervals and objective functions, the proposed method provided distributions of parameter space. Field data have been collected and applied to validate calibration capacity of GA. Dynamic calibration was suggested to capture periodic variations of inflow concentrations. Also, in order to verify this proposed method in real wastewater treatment plant, measured data sets for substrate concentrations were obtained from Haeundae wastewater treatment plant and used to estimate parameters in the dynamic system. The simulation results with calibrated parameters matched well with the observed concentrations of effluent COD.

Algorithms↗

Out-of-hospital cardiac arrest in men and women.

BACKGROUND: The incidence of sudden cardiac death is roughly 3 times greater in men than in women. However, in patients treated for out-of-hospital cardiac arrest, the relationships between sex and survival after adjustment for age and cardiac rhythm are unclear. METHODS AND RESULTS: In this retrospective cohort study, we examined 7069 men and 2582 women who were treated for out-of-hospital cardiac arrest in Seattle and suburban King County between 1990 and 1998. We compared successful prehospital resuscitation (hospital admission) and survival from event to discharge in men and women. Women had markedly reduced rates of ventricular fibrillation (VF), slightly older age, fewer witnessed arrests, and fewer arrests in public locations than men. Although their unadjusted resuscitation rate was lower (29% versus 32%, P<0.0001), women had a greater likelihood of resuscitation than men after adjustment for VF (odds ratio [OR] 1.13; 95% confidence interval [CI], 1.03 to 1.25) and after adjustment for VF plus additional factors (OR, 1.27; 95% CI, 1.14 to 1.41). The difference in resuscitation rates between men and women decreased as they aged (test for trend, P<0.0001). Unadjusted survival rates were also lower in women than in men (11% versus 15%, P<0.0001). Women had similar survival after adjustment for VF (OR, 0.97; 95% CI, 0.85 to 1.11) and after adjustment for VF plus additional factors (OR, 1.09; 95% CI, 0.93 to 1.27). CONCLUSIONS: The lower unadjusted resuscitation and survival rates observed in women were primarily due to women's lower incidence of VF, a relatively favorable cardiac rhythm. After adjustment for VF and other factors, women had higher resuscitation rates than men, but similar rates of survival from event to discharge.

Adult↗

Electroacupuncture-related changes of NADPH-diaphorase and neuronal nitric oxide synthase in the brainstem of spontaneously hypertensive rats.

The aim of this study was to investigate the electroacupuncture-related changes of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) and neuronal nitric oxide synthase (nNOS) in the brainstem of spontaneously hypertensive rats (SHR). We evaluated the changes of NADPH-d-positive neurons using a histochemical method and the changes of nNOS-positive neurons using an immunohistochemical method. The staining intensities of NADPH-d-positive neurons and nNOS-positive neurons were assessed in a quantitative fashion using a microdensitometrical method based on optical density by means of an image analyzer. The optical density of NADPH-d-positive neurons and nNOS-positive neurons of the Shinsu (BL23) and Choksamni (ST36) electroacupuncture groups were significantly decreased in most brainstem areas as compared to the normal and arbitrary groups, with the exception of the optical density of NADPH-d positive neurons in the prepositus nucleus as compared to the arbitrary group. The present results demonstrated that electroacupuncture changes the activity in the NO system in the brainstem of SHR and the site where electroacupuncture is administered is of importance for this effect.

Animals↗

Cerebral activation and distribution of inducible hsp110 and hsp70 mRNAs following focal ischemia in rat.

A potential function for inducible heat shock protein 70 (hsp70i) expression in the pathophysiology of ischemic brain has been well documented. The recently cloned hsp70 superfamily member, hsp110, was shown to be highly expressed in the brain and suggested to have a similar functional property as members of the hsp70 family. In this study, as an initial step to probe for its physiological significance in the ischemic brain, cerebral activation and distribution of hsp110 mRNA was comparatively evaluated with that of hsp70i mRNA by in situ hybridization. A rat focal cerebral ischemia model was employed to examine the distribution and localization of hsp110 and hsp70i mRNAs in both affected (ipsilateral) and unaffected (contralateral) hemispheres of the same animal. Our results demonstrated a significant accumulation of hsp110 as well as hsp70i mRNAs following ischemia; although the magnitude and kinetics of induction differ slightly, spatial expression profiles of hsp110 and hsp70i mRNAs were highly correlated in the affected region. In control brain, limited hybridization signal was observed with 3'-untranslated region (UTR) containing hsp110 probe, suggesting a possible existence of inducible hsp110 and a selective recognition of our 3'-UTR containing probe for the inducible hsp110 mRNA species. Subsequent 2D western analysis with Hsp110 specific Ab was consistent with our view, which resolved constitutive and inducible immunostained spots in rat ischemic brain. Considering a regulatory similarity as well as previously documented structural and functional similarities between hsp110 and hsp70i, we propose that coordinated cerebral activation of hsp110 and hsp70i is likely to be of significant relevance in the context of pathophysiology of ischemic brain. Further study is required to characterize the genetic and biochemical nature of rat inducible hsp110 identified in the current study.

Animals↗

Spinal lordosis with marked opisthotonus secondary to dystonia musculorum deformans: case report with surgical management.

STUDY DESIGN: A case report of severe spinal lordosis with marked opisthotonus and retrocollis secondary to dystonia musculorum deformans is presented. OBJECTIVE: To describe a case of dystonia musculorum deformans with progressive spinal lordosis and its surgical treatment. SUMMARY OF BACKGROUND DATA: Four patients with correction of coronal spinal deformity associated with dystonia musculorum deformans have been reported in the literature. No reports of sagittal spinal deformity treated with surgical instrumentation and fusion were found. METHODS: A retrospective chart and radiographic review of a single case was conducted. RESULTS: Orthotic management and pharmacologic therapy with botulinum toxin injections were unsuccessful in controlling the deformity. Severe spinal lordosis (170 degrees ) from occiput to sacrum was corrected surgically, allowing an upright posture. CONCLUSION: Dystonia musculorum deformans is a rare condition resulting in coronal or sagittal plane deformities. When other treatment methods are unsuccessful, surgical instrumentation and arthrodesis may correct the deformity and improve function.

Adolescent↗

Genome-wide chromatin remodeling modulates the Alu heat shock response.

During heat shock recovery in Hela cells, the level of Alu RNA transiently increases with kinetics that approximately parallel the transient expression of heat shock protein mRNAs. Coincidentally, there is a transient increase in the accessibility of Alu chromatin to restriction enzyme cleavage suggesting that an opening and re-closing of chromatin regulates the Alu stress response. Similar changes occur in alpha satellite and LINE1 chromatin showing that heat shock induces a genome-wide remodeling of chromatin structure which is independent of transcription. The increased accessibility of restriction sites within these repetitive sequences is inconsistent with a simple lengthening of the nucleosome linker region but instead suggests a scrambling of nucleosome positions. Chromatin structure and its dynamics account for many of the principal features of SINE transcriptional regulation potentially providing a functional rationale for the dispersion and high copy number of SINEs.

Alu Elements↗

N-terminal processing is essential for release of epithin, a mouse type II membrane serine protease.

Epithin was originally identified as a mouse type II membrane serine protease. Its human orthologue membrane type-serine protease 1 (MT-SP1)/matriptase has been reported to be localized on the plasma membrane. In addition, soluble forms of matriptase were isolated from human breast milk and breast cancer cell-conditioned medium. In this paper, we report a processing mechanism that appears to be required for the release of epithin. CHO-K1 or COS7 cells transfected with single full-length epithin cDNA generated two different-sized proteins in cell lysates, 110 and 92 kDa. The 92-kDa epithin was found to be an N-terminally truncated form of the 110-kDa epithin, and it was the only form detected in the culture medium. The 92-kDa epithin was also found on the cell surface, where it was anchored by the N-terminal fragment. The results of in vivo cell labeling experiments indicate that the 110-kDa epithin is rapidly processed to the 92-kDa epithin. Using site-directed mutagenesis experiments, we identified Gly(149) of the GSVIA sequence in epithin as required for the processing and release of the protein. These results suggest that N-terminal processing of epithin at Gly(149) is a necessary prerequisite step for release of the protein.

Animals↗

Anomalous electronic structure and pseudogap effects in Nd1.85Ce0.15CuO4.

We report a high-resolution angle-resolved photoemission spectroscopic study of the electron-doped ( n-type) cuprate superconductor Nd1.85Ce0.15CuO4. We observe regions along the Fermi surface where the near- E(F) intensity is suppressed and the spectral features are broad in a manner reminiscent of the high-energy "pseudogap" in the underdoped p-type (hole doped) cuprates. However, instead of occurring near the (pi,0) region, as in the p-type materials, this pseudogap falls near the intersection of the underlying Fermi surface with the antiferromagnetic Brillouin zone boundary.

Journal Article↗

Diabetes and depot medroxyprogesterone contraception in Navajo women.

BACKGROUND: Depot medroxyprogesterone acetate contraception is widely used in Navajo women, a high-risk population for diabetes mellitus. However, depot medroxyprogesterone may lead to weight gain and independently decrease insulin sensitivity. We studied the association between depot medroxyprogesterone and development of diabetes in Navajo women. METHODS: We studied Navajo women aged 18 to 50 years who had seen a health care provider at a Navajo Area Indian Health Service clinic at least once in 1998. Diabetic cases (n = 284) and nondiabetic controls (n = 570) were matched by age. Medical records were reviewed to determine contraception use before the diagnosis date of diabetes. RESULTS: Users of depot medroxyprogesterone were more likely to develop diabetes than patients who had used combination estrogen-progestin oral contraception only (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.8-7.9). The excess risk persisted after adjustment for body mass index (OR, 3.6; 95% CI, 1.6-7.9). Longer use was associated with greater risk of diabetes. Users of depot medroxyprogesterone were also more likely to develop diabetes than patients who had never used hormonal contraception, although excess risk was smaller (OR, 2.4; 95% CI, 1.4-3.6). CONCLUSIONS: Depot medroxyprogesterone contraception was associated with a greater risk of diabetes compared with combination oral contraceptive use only. Risk was associated with length of use and persisted after adjustment for body mass index. Additional research is needed for confirmation, but this risk should be considered in contraceptive choice for women at high risk for diabetes.

Adult↗

Cancer isoform of a tumor-associated cell surface NADH oxidase (tNOX) has properties of a prion.

We have described a drug-responsive form of a cell surface NADH oxidase (hydroquinone oxidase) of cancer cells (tNOX) that exhibits unusual characteristics including resistance to proteases, resistance to cyanogen bromide digestion, and an ability to form amyloid filaments closely resembling those of spongiform encephalopathies and all of which are characteristics of PrP(sc) (PrP(res)), the presumed infective and proteinase K resistant particle of the scrapie prion. The tNOX protein from the HeLa cell surface copurified with authentic glyceraldehyde-3-phosphate dehydrogenase (muscle form) (GAPDH). Surprisingly, the tNOX-associated muscle GAPDH also was proteinase K resistant. In this paper, we show that combination of authentic rabbit muscle GAPDH with tNOX renders the GAPDH resistant to proteinase K digestion. This property, that of converting the normal form of a protein into a likeness of itself, is one of the defining characteristics of the group of proteins designated as prions.

Animals↗

Bilayer splitting in the electronic structure of heavily overdoped Bi(2)Sr(2)CaCu(2)O(8+delta).

The electronic structure of heavily overdoped Bi(2)Sr(2)CaCu(2)O(8+delta) is investigated by angle-resolved photoemission spectroscopy. The long-sought bilayer band splitting in this two-plane system is observed in both normal and superconducting states, which qualitatively agrees with the bilayer Hubbard model calculations. The maximum bilayer energy splitting is about 88 meV for the normal state feature, while it is only about 20 meV for the superconducting peak.

Journal Article↗

Development of a novel dosage form for intramuscular injection of titrated extract of Centella asiatica in a mixed micellar system.

Titrated extract of Centella asiatica (TECA), a drug used in treating systemic scleroderma, is poorly water-soluble. A conventional dosage form for the intramuscular injection of TECA, propylene glycol (PG)-based TECA solution, causes severe pain after intramuscular injection. To improve the solubility of TECA and reduce pain after injection, mixed micellar systems composed of 10% surfactant mixture (Tween 20 and Tween 85) and 90% phosphate-buffered saline, pH 7.0 (PBS) were prepared. As the ratio of Tween 20 to Tween 85 increased from 0:10 to 10:0, the solubility of TECA in the mixed micellar systems increased from 7- to 26-fold compared to that in PBS (pH 7.0). The droplet size of micelles gradually decreased with the increasing ratio of Tween 20 to Tween 85 from 0:10 to 4:6, followed by an abrupt decrease in size above the ratio of 6:4. Furthermore, the micellar systems prepared with Tween 20 and Tween 85 at the ratio of 6:4, 8:2 or 10:0 could solubilize TECA more than 10 mg/ml and the resultant droplet sizes were less than 2 microm. No significant changes were observed in the droplet sizes and asiaticoside contents in these micellar formulations during storage, indicating these systems are stable for at least 60 days. Their osmotic pressures were remarkably lower than those of PG-based TECA solution and similar to that of saline solution, irrespective of dilution ratios. Most importantly, they markedly reduced the number of writhes compared with PG-based TECA solution after injection to mice. All of these results suggest that these three TECA micellar formulations prepared with Tween 20 and Tween 85 improved the solubility of TECA and reduced pain following injection, possibly due to the decrease in osmotic pressure. Thus, these micellar formulations composed of optimum ratios of Tween 20 and Tween 85 may have a potential as dosage forms for the intramuscular injection of a poorly water-soluble TECA.

Animals↗