Management of problem cases in cochlear implantation.
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Adolescent↗
Biomedical subjects
C S Kim
Publications and source records attributed to C S Kim.
Speech perception abilities in prelingually deafened Korean-speaking children using multichannel cochlear implants.
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Child↗
Auditory cortical activity in cochlear implantees before and after sound stimulation using positron emission tomography.
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Acoustic Stimulation↗
Comparative measurement of lung deposition of inhaled fine particles in normal subjects and patients with obstructive airway disease.
Particulate pollutants have been suggested as a risk factor for increase in mortality and morbidity in patients with obstructive airway disease. In the present study we hypothesized that enhanced particle deposition dose is an underlying factor for such a finding. We measured lung deposition in normal healthy control subjects (N; n = 10) and in subjects with varying levels of airway obstruction: smokers (S; n = 10), smokers with small airways disease (SAD; n = 10), asthmatics (A; n = 5), and patients with chronic obstructive airway disease (COPD; n = 10). The subjects inhaled a uniform size sebacate aerosol (1-micron diameter) from a collapsible bag of a known volume (500 ml) repeatedly for as many as 15 breaths at a rate of 30 breaths/min. Aerosol concentration was monitored continuously at the mouth by a laser aerosol photometer. After correcting for particle loss in the bag, lung deposition fraction [DF = (inhaled minus exhaled)/inhaled], was determined breath by breath. DF values (mean +/- SD) were 0.14 +/- 0.02, 0.16 +/- 0.02, 0.21 +/- 0.05, 0.22 +/- 0.02 and 0.028 +/- 0.03 for N, S, SAD, A, and COPD, respectively. DF values in S, SAD, A, and COPD were 16, 49, 59, and 103% greater, respectively, than that of normal subjects (p < 0.05). DF of COPD was also greater than that of SAD or A (p < 0.05). No difference was found between SAD and A. When all of the subject data were combined, DF was correlated well with percent predicted FEV1 and FEF25-75 (r2 = 0.63 in both). The results indicate a marked increase in particle deposition in patients with obstructive lung disease, and this can be an important factor for the development of the adverse health effects of pollutant particles on the one hand and for the treatment of patients with drug aerosols on the other.
Administration, Inhalation↗
Inflammatory cytokine expression on nasal polyps developed in allergic and infectious rhinitis.
To investigate the expression of cytokine mRNAs in nasal polyps and the role of allergy in the pathogenesis of nasal polyposis, we studied the expression of IL-4, IL-5, and IFN-gamma mRNAs using the RT-PCR and Southern blot. Nasal polyp specimens were obtained from 14 patients with infectious rhinitis and 5 patients with perennial allergic rhinitis. Turbinate mucosa specimens were obtained from 10 patients with allergic rhinitis and from 10 healthy subjects as controls. IL-4, IL-5 and IFN-gamma mRNA were expressed in most specimens of allergic turbinate mucosa. The expression of these cytokines was less frequent in normal healthy turbinate mucosa. The density ratios of IL-4, IL-5 and IFN-gamma to beta-actin were individually determined in both polyp and turbinate tissues. The density ratio for each cytokine was relatively higher in polyp tissues than in healthy turbinate mucosa; however, there was no significant difference in the density ratios determined for polyps associated with allergic rhinitis as compared with polyps associated with infectious rhinitis. These findings indicate that nasal polyposis may differ from allergic rhinitis in the mechanism by which IL-4 and IL-5 are increased. It is concluded that allergy may have an insignificant role in the development of nasal polyps.
Adult↗
Fenretinide: induction of apoptosis and endogenous transforming growth factor beta in PC-3 prostate cancer cells.
N-(4-Hydroxyphenyl)retinamide (4-HPR, Fenretinide) is a retinoid derivative with antineoplastic activity in various tumor types including prostate carcinoma. The mechanism of action of 4-HPR toxicity is unknown. 4-HPR induces apoptosis in leukemia- and lymphoma-derived cells, neuroblastoma, and small cell lung cancers. The present study was designed to investigate: (a) the mechanism of 4-HPR cytotoxicity in prostate cancer cells; and (b) correlate increased expression of transforming growth factor beta 1 (TGF beta 1) with induction of apoptosis. 4-HPR exposure to PC-3 cells in vitro was associated with apoptosis as evidenced by increased incidence of hypodiploid nuclei in propidium iodide fluorescence histograms and DNA fragmentation. An increase in the percentage of nuclei in the G1 phase of the cell cycle preceded induction of apoptosis. TGF beta 1-increased expression was noted in mRNA levels and in secretion of active TGF beta 1 into culture media. TGF beta 1 and TGF-beta receptor type II detected immunohistochemically were increased in 4-HPR-treated PC-3 cells. Furthermore, 4-HPR-induced cytotoxicity in PC-3 cells was abrogated by the addition of anti-TGF beta 1 antibody. In BT-20 cells, a 4-HPR-resistant breast carcinoma cell line, apoptosis was not observed after exposure to 4-HPR nor was TGF beta 1 expression enhanced in stained cells or in conditioned media. It is concluded that 4-HPR induces the expression of TGF beta 1 in association with the induction of apoptosis.
Antineoplastic Agents↗
Cloning of cDNAs coding for heavy- and light-chain variable regions of a murine monoclonal antibody with specificity for human plasma apolipoprotein A-I.
We prepared a monoclonal antibody (mAb) A-I4-48 to HDL apolipoprotein A-I with the ultimate goals of expressing the valuable immunodiagnostic single-chain Fv (scFv) in Escherichia coli. The binding specificity of mAb A-I4-48 was determined by ELISA and Western blot analysis. The dissociation constant (Kd) of antigen-antibody complex obtained by ELISA was 8.33 x 10(-8) M. Poly(A)+ RNA was prepared from the hybridoma cell line secreting mAb A-I4-48 and used as a template for cDNA synthesis and cloning. The nucleotide sequence analyses revealed that the variable regions of the heavy- and light-chains were members of mouse heavy-chain subgroup IIA and kappa light-chain subgroup II, respectively. Comparison of the nucleotide sequences with mouse immunoglobulin genes in the GenBank data base showed that the cDNAs have not been previously reported.
Amino Acid Sequence↗
Distribution of 2,4-dichlorophenoxyacetic acid (2,4-D) in maternal and fetal rabbits.
The distribution of 2,4-dichlorophenoxyacetic acid (2,4-D) was examined in maternal and fetal rabbits. Pregnant New Zealand rabbits (28-30 d gestational age) were anesthetized with ketamine/xylazine and the femoral vein and artery were catheterized for compound administration and sampling. Dams received iv [14C]2,4-D (12.5 microCi/kg) with unlabeled sodium 2,4-D (1, 10, or 40 mg/kg) in saline. Blood and tissue were collected up to 2 h after dosing. Fetal to maternal plasma AUC ratios were 0.09, 0.07, and 0.16 after the 1, 10, or 40 mg/kg dose, respectively. Extraplasma AUCs were greatest in maternal kidney and uterus and lowest in maternal and fetal brain. A greater than fourfold elevation in fetal AUC was found when the dose was increased from 10 to 40 mg/kg, suggesting saturation of maternal plasma binding of 2,4-D. Although the in vitro fetal brain tissue to incubation media ratio was unity (1.03 +/- 0.1, mean +/- SD), fetal brain AUCs were 10% or less of the fetal plasma AUCs, indicating the brain barrier system to 2,4-D is functioning in the late-gestation fetal rabbit. However, its development may not be complete due to the higher brain tissue to plasma ratios in the fetus compared to the dam.
2,4-Dichlorophenoxyacetic Acid↗
Induction of apoptosis by diethylstilbestrol in hormone-insensitive prostate cancer cells.
BACKGROUND: Diethylstillbestrol (DES) and diethylstilbestrol diphosphate (DESdP) are effective agents for the treatment of advanced prostate cancers. Tumor-inhibiting effects of DES and DESdP are presumed secondary to suppression of androgen production in vivo. Little is known, however, about the direct cellular mechanisms of the tumor inhibition. Estrogens have been reported not only to stimulate growth but also to disrupt microtubule formation in prostate cancer cells. PURPOSE: The study was designed to examine and compare mechanisms of in vitro growth inhibition of DES and DESdP in human androgen-insensitive prostate cancer cells (DU145, 1-LN, and PC-3) and human androgen-sensitive prostate cancer cells (LNCaP) and to examine estrogen receptor modulation of such effects. METHODS: The cytotoxic effects of DES and DESdP were examined in vitro by use of a standard microculture tetrazolium assay to quantitate numbers of viable cells. Immunofluorescence microscopy, DNA fragmentation analysis, and fluorescence flow cytometry were used to investigate microtubules, the induction of apoptosis, and changes in cell cycle distribution. The degree of estrogen receptor positivity of untreated and treated cells was determined by immunohistochemistry and quantitative image analysis. RESULTS: LD50 levels (the dose at which 50% of cells are no longer viable) in the concentration range of 19-25 microM were observed for both DES and DESdP in all cell lines examined. DESdP-induced growth inhibition was found to be dependent on heat-labile phosphatases present in fetal calf serum. DES-induced cytotoxicity was not affected by the presence of 17 beta-estradiol, and it was not dependent on the presence of estrogen receptor. Estrogen receptor-positive cells and estrogen receptor-negative cells were equally responsive to DES. PC-3 cells stained with fluorescent anti-tubulin, phalloidin (actin stain), and 4',6-diamidino-2-phenylindole (DNA stain) showed no inhibition of microtubules or actin filaments but revealed the presence of apoptotic bodies in the nuclei. Fluorescence flow cytometry of nuclear DNA content of propidium iodide-stained nuclei from androgen-insensitive prostate cancer cells treated with 15 or 30 microM DES or DESdP revealed an increase in relative numbers of hypodiploid (apoptotic) nuclei, a depletion of G1- and S-phase cells, and an accumulation of cells in G2/M phase. Conversely, androgen-sensitive cells contained a lower percentage of hypodiploid nuclei but no accumulation of cells in G2/M phase. CONCLUSIONS: Direct cytotoxic effects of DES in prostate cancer cells are estrogen receptor independent and do not involve disruption of microtubule architecture but do involve the promotion of cell cycle arrest and apoptosis. These are the first data confirming direct cytotoxic effects of DES and DESdP in prostate cancer cells via an apoptotic mechanism. IMPLICATIONS. These results suggest that DES and DESdP have potential value as agents against androgen-insensitive prostate neoplasms through induction of an apoptotic cascade.
Antineoplastic Agents, Hormonal↗
Kinetic analysis of glutamate transport by the miniswine choroid plexus in vitro.
Transport of glutamic acid by the choroid plexus, the blood-cerebrospinal fluid (CSF) barrier, was investigated by using the isolated choroid plexi from the fourth (FVCP) and lateral ventricles (LVCP) of the young adult miniswine in vitro. Glutamic acid uptake was very pronounced, with concentrations 7-fold (LVCP) and 2.4-fold (FVCP) higher in tissue than in medium after only 5 min of incubation with 1 microM glutamic acid. Tissue/medium ratios reached steady state by 15 min at 30-fold (LVCP) and 11-fold (FVCP). Uptake was energy-dependent and inhibited by ouabain and hypothermia. L-Aspartic acid was shown to be inhibitory in a concentration-dependent manner, suggesting that it shares a common transport system, whereas neither octanoic acid nor okadaic acid (transported by a separate fatty acid system) inhibited glutamic acid transport. At the same temperature, the labeled metabolite of glutamate (glutamine) in the tissue was 64.7%, 73.2%, and 72.5% of total radioactivity at 5, 30, and 60 min, respectively. The estimated Km values for glutamate uptake by the choroid plexus are 264 microM (FVCP) and 196 microM (LVCP); Vmax values are 87 (FVCP) and 147 (LVCP) nmol/g/min, respectively. These results indicate that, in addition to the metabolism of glutamate to glutamine, an active uptake mechanism is present in the choroid plexus of miniswine which may serve to regulate glutamic acid concentration in the CSF.
Animals↗
Construction of a physiologically based pharmacokinetic model for 2,4-dichlorophenoxyacetic acid dosimetry in the developing rabbit brain.
A physiologically based pharmacokinetic (PBPK) model that describes the kinetics of organic anions by using 2,4-dichlorophenoxyacetic (2,4-D) as a representative compound was constructed for the developing rabbit brain at near-term pregnancy (Gestation Day 30). The model consisted of brain, body, and venous and arterial compartments for the mother which were linked to the fetus by a placenta. Maternal brain compartments in the model were brain plasma, cerebrospinal fluid (CSF), and brain tissue including hypothalamus, caudate nucleus, hippocampus, forebrain, brainstem, and cerebellum. The fetus consisted of brain, body, amniotic fluid, and venous and arterial compartments. the maternal body had both a central and a deep compartment; the fetal body had only one compartment. Maternal blood flow to the fetus was modeled as blood flowing to the placenta, where it was equilibrated before it reached the fetus. The brain uptake was membrane-limited by the blood-brain barrier, with saturable clearance from the CSF into the venous blood by the choroid plexus in both fetus and mother. The model was used to compare concentrations of 2,4-D in maternal and fetal brain, maternal and fetal plasma, and amniotic fluid over time with experimental data from pregnant rabbits given 2,4-D intravenously (1, 10, or 40 mg/kg). The model adequately simulated the 2-hr time course of 2,4-D concentrations in both mother and fetus. With continued development, this generic PBPK model should be a useful tool for evaluating the safety of organic acid neurotoxicants in the developing brain.
2,4-Dichlorophenoxyacetic Acid↗
Pitfalls of nonoperative management of blunt abdominal trauma in children in Korea.
During the past decade, the nonoperative management of children with blunt abdominal trauma without operation has improved dramatically by virtue of the development of medical technology. However, missed injuries or complications after nonoperative management often are associated with serious morbidity. The authors evaluated 86 patients between 1990 and 1994 who had intraabdominal solid-organ injury (excluding retroperitoneal organs) owing to blunt trauma. The liver was injured in 43 cases, the spleen in 36, and the pancreas in 14. Initially, 68 patients (79%) were managed conservatively and 18 underwent surgery because of unstable vital signs or associated injuries. Three patients had delayed surgery more than 48 hours after trauma) because of initially missed injuries (complete infarction of the spleen, duodenal injury, major pancreatic injury). Eleven patients (17%) with nonoperative management had a total of 13 complications. The most common complications were pleural effusion and atelectasis. One patient had prolonged ileus owing to delayed absorption of an intraperitoneal hematoma, and the symptom was relieved by aspiration of the hematoma. A huge hepatic subcapsular hematoma developed in another patient and required percutaneous drainage with a pigtail catheter for 5 weeks. A pancreatic pseudocyst detected on the 16th hospital day also was drained with a pigtail catheter. A splenic abscess developed in another patient 24 days after a splenic injury, which was treated with ultrasound-guided aspiration. No patients died as a result of nonoperative management. In conclusion, even though patients with blunt abdominal trauma are stabilized and nonoperative management decided on, careful follow-up for a prolonged period is still necessary to prevent missed injuries or late complications.
Abdominal Injuries↗
p53 mutations in solar keratoses.
To understand how sunlight acts as a carcinogen, the authors analyzed p53 gene mutations including point mutation, loss of heterozygosity (LOH), and overexpression in solar keratoses. Exons 4 to 9 of the p53 gene were amplified by polymerase chain reaction (PCR) and directly sequenced. To determine allelic loss of p53, the region containing polymorphic codon 72 was amplified and digested with BstUI restriction nuclease. Overexpression of p53 protein was detected in paraffin section using mouse monoclonal antibody (PAb 1801). Point mutations of the p53 gene were detected in 7 (28%) of 25 solar keratoses and predominant in pyrimidines (86%). Loss of allele was found in 29% of informative samples. Seven (28%) cases showed immunopositivity; four cases had point mutation, but three cases did not. Two cases with point mutation were immunonegative. Characteristically point mutations, LOH and immunopositivity of p53 were seen predominantly as bowenoid and hypertrophic type lesion. These results suggest that sunlight can cause mutations of p53 gene and that p53 gene mutations may play an important role in skin carcinogenesis.
Genes, p53↗
Contact laser turbinate surgery for the treatment of idiopathic rhinitis.
To evaluate the value of contact laser turbinate surgery using a diode laser in the treatment of idiopathic rhinitis. 53 patients were examined before and after surgery. Six months following surgery, nasal obstruction was significantly improved and a significant decrease in nasal airway resistance was noted on active rhinomanometric measurements (P < 0.05). There were no significant post-operative changes in olfactory acuity using the butanol threshold test and in mucociliary transport using the saccharin transit time. The results of this study suggest that contact laser turbinate surgery may be a valuable alternative form of surgical treatments for patients with idiopathic rhinitis.
Adult↗
Esophagorespiratory fistulae due to esophageal carcinoma: palliation with a covered Gianturco stent.
PURPOSE: To evaluate therapeutic effects and complications of a covered Gianturco stent for esophagorespiratory fistulae. MATERIALS AND METHODS: Of 95 patients with esophageal carcinomas, 10 had esophagorespiratory fistulae and were treated with a silicone-covered Gianturco stent. The authors retrospectively assessed patients' food intake capacity and delayed problem of the stent. RESULTS: All fistulae were occluded without immediate complications. Two patients could swallow all foods; four, most foods; three soft foods; and one, only liquids. Clinical problems occurred between 1 and 24 weeks in four patients: reopened fistula (n = 1), recurrent fistula (n = 1) (both patients were successfully treated with another esophageal stent), and dyspnea (n = 2) due to tracheal compression by stent and tracheal invasion by tumor (one patient was treated with a tracheal stent). CONCLUSION: A silicone-covered modified Gianturco stent is effective for palliation of esophagorespiratory fistulae caused by esophageal cancer. Simultaneous use of a tracheal stent is recommended for extrinsic tracheal narrowing by the proximal tip of the stent and invasion by tumor.
Bronchial Fistula↗
Assessment of regional deposition of inhaled particles in human lungs by serial bolus delivery method.
Detailed regional deposition of inhaled particles was investigated in young adults (n = 11) by use of a serial bolus aerosol delivery technique. A small bolus (45 ml half-width) of monodisperse aerosols [1-, 3-, and 5-microns particle diameter (Dp)] was delivered sequentially to a specific volumetric depth of the lung (100-500 ml in 50-ml increments), while the subject inhaled clean air via a laser aerosol photometer (25-ml dead volume) with a constant flow rate (Q = 150, 250, and 500 ml/s) and exhaled with the same Q without a pause to the residual volume. Deposition efficiency (LDE) and deposition fraction in 10 local volumetric regions and total deposition fraction of the lung were obtained. LDE increased monotonically with increasing lung depth for all three Dp. LDE was greater with smaller Q values in all lung regions. Deposition was distributed fairly evenly throughout the lung regions with a tendency for an enhancement in the distal lung regions for Dp = 1 micron. Deposition distribution was highly uneven for Dp = 3 and 5 microns, and the region of the peak deposition shifted toward the proximal regions with increasing Dp. Surface dose was 1-5 times greater in the small airway regions and 2-17 times greater in the large airway regions than in the alveolar regions. The results suggest that local or regional enhancement of deposition occurs in healthy subjects and that the local enhancement can be an important factor in health risk assessment of inhaled particles.
Administration, Inhalation↗
Interleukin-1 alpha, interleukin-1 beta and interleukin-8 gene expression in human aural cholesteatomas.
Bone destruction is a common characteristic feature of chronic otitis media, especially aural cholesteatoma. A number of immunohistochemical studies have suggested that interleukin-1 (IL-1) may be responsible for cholesteatomatous bone destruction. We designed this study to present the mRNA expression patterns of IL-1 alpha, IL-1 beta, and IL-8, which can induce and activate the leukocyte, the major reservoir of potent proteolytic enzymes. Total RNAs were extracted from aural cholesteatomas, external auditory canal skin (EACS), postauricular skin (PAS), and granulation tissues and transcribed into cDNAs. cDNAs were amplified by using PCR technique with primers for IL-1 alpha, IL-1 beta, IL-8, and beta-actin. Amplified products were hybridized with each internal probe and the relative density was measured. In granulation tissues, the relative density of IL-1 alpha was greater than that of other tissues. The ratio of IL-1 beta and IL-8 of aural cholesteatoma was significantly higher than that of EACS and PAS. We suggest that both of IL-1 alpha and IL-1 beta may play a role in the pathological changes, and that IL-8, which is mainly produced from cholesteatomatous epithelium, may have an important role in the pathological changes of cholesteatomas.
Blotting, Southern↗
Effects of ischemia-hypoxia induced by interruption of uterine blood flow on fetal rat liver and brain enzyme activities and offspring behavior.
The effects of acute perinatal ischemia-hypoxia on fetal liver and brain energy metabolism, fetal brain total free fatty acid concentration and subsequent offspring behavior were investigated in rats. Ischemia-hypoxia was induced at term either by ligation of the uterine blood vessels or submersion of the entire uterine horn in warmed saline. Fetuses of the adjacent horn served as within-dam controls for all assessments and fetuses of dams which had not undergone the surgical stress served as independent controls for enzyme assays. Ischemia-hypoxia was associated with reduced activity of fatty acid synthase in the liver and brain. Total free fatty acid concentration significantly increased in the fetal hypoxic brain. Pups not used for enzyme analyses were cross-fostered for behavioral assessments. Relative to the enzymatic alterations, there were few behavioral alterations associated with ischemia-hypoxia. At postnatal day 30, rats made hypoxic by ligation of the uterine blood vessels had decreased caudate nucleus and brain stem weights relative to within-dam controls. At postnatal day 85, rats made hypoxic by submersion of the uterine horn had decreased olfactory bulb weight. The results of this study indicate an initial acute response to a brief period of ischemia-hypoxia at term pregnancy in the fetal rat brain and liver.
Age Factors↗