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Biomedical subjects

S Kim

Publications and source records attributed to S Kim.

At least 433 records · Page 24Linked to original sources

Preliminary acute and subchronic toxicity studies of GLG-V-13, a novel class III antiarrhythmic agent, in mice.

The acute and subchronic toxic effects of GLG-V-13 (3-[4-(1H-imidazol-1-yl)benzoyl]-7-isopropyl-3,7-diazabicyclo[3.3.1]nona ne dihydroperchlorate, CAS 155029-33-7), a novel class III with some class Ib antiarrhythmic activity, were investigated in mice. The estimated LD50 for GLG-V-13 given orally were 419 mg/kg for male mice and 383 mg/kg for female mice, respectively. The acute toxic signs appeared to be of the central nervous system in origin. Four groups of mice (15 per sex, group and dose) were fed daily with diets containing GLG-V-13 for 90 consecutive days. The equivalent daily doses were 0, 22, 50 and 121 mg/kg/day and 0, 27, 60 and 136 mg/kg/day for male and female mice, respectively. All of the mice survived. Food consumption was decreased. However, mean body weight and body weight gain were not significantly changed. Gross pathological changes, especially in the lungs and liver, were found in the middle and high dose groups. Consistent increased mean corpuscular hemoglobin concentration and decreased mean corpuscular hemoglobin were observed in all dose groups. Hepatocellular necrosis was found in both male and female mice treated with the drug and was dose-dependent. Marked vacuolation of the X zone in the adrenal gland with mild to moderate deposition of ceroid pigments (brown degeneration) was observed in female mice. Lesions in the kidneys and adrenal glands may be a possible reason for changes in serum sodium and potassium ions concentrations leading to an increase in water intake. A significant reduction in cholesterol in the high dose group may be a favorable pharmacological effect of GLG-V-13. The data from the 90-day subchronic toxicity studies indicate that GLG-V-13 appears to have limited systemic toxicity potential.

Animals↗

Successful endoscopic resection of intramural metastasis after esophagectomy for esophageal cancer: a case report.

Carcinoma of the esophagus is often accompanied by intramural metastasis (IM) at the time of diagnosis, and the prognosis of patients with such metastasis is very poor. Here we report the case of a 60-year-old man who presented with a submucosal tumor in the wall of the cervical esophagus at 2 years after esophagectomy for thoracic esophageal cancer. The tumor was resected endoscopically and was histologically shown to be an IM of esophageal cancer. He has shown no recurrence and no metastasis during 2 years of follow-up after endoscopic resection and radiation therapy.

Carcinoma, Squamous Cell↗

The nutrition transition in South Korea.

BACKGROUND: An accelerating shift from infectious to noncommunicable diseases and concurrent shifts in diet, activity, and body composition are universal trends but are especially apparent in middle- and lower-income countries. A unique nutrition transition has occurred in South Korea, a country that modernized earlier than most Asian countries did. OBJECTIVE: The purpose of this analysis was to describe the South Korean nutrition transition, focusing on specific features that other countries might follow to retain the healthful elements of their traditional diets. DESIGN: We used secondary data on economics, dietary intake, anthropometry, and causes of death, including a series of comparable nationally representative dietary surveys (the National Nutrition Survey). RESULTS: The structure of South Korea's economy, along with the country's dietary and disease patterns, began an accelerated shift in the 1970s. Major dietary changes included a large increase in the consumption of animal food products and a fall in total cereal intake. Uniquely, the amount and rate of increase in fat intake have remained low in South Korea. South Korea also has a relatively low prevalence of obesity compared with other Asian countries with similar or much lower incomes. CONCLUSIONS: The nutrition transition in South Korea is unique. National efforts to retain elements of the traditional diet are thought to have shaped this transition in South Korea in the midst of rapid economic growth and the introduction of Western culture.

Adolescent↗

Inhibitory effects of 1,3-diaminopropane, an ornithine decarboxylase inhibitor, on rat two-stage urinary bladder carcinogenesis initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine.

Overexpression of ornithine decarboxylase (ODC) has been shown to be characteristic of tumor development and progression in humans and experimental animals. Therefore, we have examined the effects of 1, 3-diaminopropane dihydrochloride (DAP), a potent inhibitor of ODC, on rat two-stage urinary bladder carcinogenesis initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). In experiment 1 (36 weeks), 6-week-old F344 male rats were administered 0.05% BBN in drinking water for 4 weeks and then divided into four groups. Animals of groups 1 and 2 received basal diet and drinking water supplemented with or without DAP (2 g/l). Groups 3 and 4 were given diet containing 5% sodium L-ascorbate (NaAsA), a typical urinary bladder tumor promoter, and drinking water with or without DAP. Administration of DAP to group 1 significantly reduced tumor size, multiplicity and incidence, particularly of papillomas, when compared with group 2 values. DAP together with NaAsA (group 3) also decreased tumor size relative to the group 4 case. To determine the effects of DAP on the early stages of bladder carcinogenesis and its mechanisms, a similar protocol was conducted (experiment 2) with death after 20 weeks. DAP treatment caused complete inhibition (0% incidence) of papillary and/or nodular hyperplasia in group 1 but was without influence in group 3, as compared with the respective controls. Moreover, the ODC activity, bromodeoxyuridine labeling indices and mRNA expression levels of cyclin D1 in the urinary bladder mucosa, determined by northern blotting, were markedly lower in group 1 than in group 2, but values were comparable for both groups administered NaAsA. Assessment of mRNA expression levels of the angiogenic vascular endothelial growth factor suggested no involvement in the inhibitory effects of DAP on urinary bladder carcinogenesis. The results indicate that inhibition of ODC could reduce urinary bladder carcinogenesis in rats, particularly in the early stages, through antiproliferative mechanisms.

Acetyltransferases↗

Accumulation of phosphorylated sphingoid long chain bases results in cell growth inhibition in Saccharomyces cerevisiae.

Sphingolipid metabolites in mammals can function as signaling molecules with cell-specific functions. In Saccharomyces cerevisiae, phosphorylated long chain bases, such as dihydrosphingosine 1-phosphate and phytosphingosine 1-phosphate, have also been implicated in stress responses. To further explore the biological roles of these molecules, we created disruption mutants for LCB4, LCB5, DPL1, YSR2, YSR3, and SUR2. LCB4 and LCB5 encode kinases that phosphorylate long chain bases. DPL1 and YSR2/YSR3 are involved in degradation of the phosphorylated long chain bases. SUR2 catalyzes conversion of dihydrosphingosine to phytosphingosine. We adapted an HPLC method to measure intracellular concentrations of the phosphorylated long chain bases. Double mutants of dpl1 and ysr2 were inviable, whereas dpl1 ysr2 lcb4 triple mutants were viable. Further, growth inhibition associated with accumulated phosphorylated long chain bases was observed in the triple mutant dpl1 ysr2 lcb4 overexpressing LCB4 or LCB5. These results indicate that phosphorylated long chain bases can inhibit cell growth. Mutants defective in both YSR2 and SUR2, which accumulated dihydrosphingosine 1-phosphate only, grew poorly. The phenotypes of the ysr2 sur2 mutants were suppressed by overexpression of DPL1. Our results clearly show that elevated levels of phosphorylated long chain bases have an antiproliferative effect in yeast.

Fungal Proteins↗

Secretory, endocrine and autocrine/paracrine function of the adipocyte.

Obesity is a major public health problem in Western countries, and >55% of adult Americans are overweight or obese. A major contributor to the epidemic of obesity is the current environment, which is characterized by increased availability of high energy foods and decreased physical activity. Several studies also demonstrated that genetic susceptibility contributes to obesity in some populations. Obesity research has focused primarily on the role of the hypothalamus in neuroendocrine regulation of food intake. However, a growing number of studies support a potential contribution of adipose tissue, via its newly discovered secretory function, to the pathogenesis of obesity and co-morbid conditions including cardiovascular disease, diabetes and hypertension. This paper will review the role of four factors secreted by adipose tissue (leptin, agouti, angiotensin II and prostaglandins) and their functions in the regulation of energy balance and whole-body homeostasis. Several other peptide and nonpeptide substances are secreted from adipose tissue; their function and regulation have been documented extensively.

Adipocytes↗

Assessment of the relationships among posture, maxillomandibular denture complex, and soft-tissue profile of aesthetic adult Korean women.

The objective of this study was to assess the relationships among the posture, the maxillomandibular denture complex, and the soft-tissue profile of aesthetic adult Korean women. From an initial group of 346 women, the authors examined 28 beautiful adult Korean women who had normal vertical and sagittal skeletal relationships and normal occlusion. There were no differences in the inclinations of the incisors to the occlusal planes in the maxilla and the mandible in the data for Korean women vs. Arnett's data for white women. However, the overbite and overjet in Korean women were slightly smaller than in white women. AB to maxillary occlusal plane angle (MxOP) represented the anteroposterior denture base discrepancy to the occlusal plane. Angulation of the maxillary occlusal plane to the Frankfurt (FH) plane and the true vertical line at submasale (TVL) (Sn) was a little steeper in Korean women than in white women. The FH plane was almost parallel to the true horizontal line in Korean women who had normal vertical and sagittal skeletal relationships and normal occlusion. With regard to soft-tissue variables, the upper lip length (Sn-Stms), interlabial gap, upper incisor exposure, nasolabial angle, lip and nose tip projection value, and TVL (Sn)-to-upper lip line (UL) angle showed interracial differences. The results of this study can assist in the diagnosis and treatment planning of orthognathic surgery.

Adult↗

Hypophosphatemic osteomalacia demonstrated by Tc-99m MDP bone scan: a case report.

Hypophosphatemic osteomalacia, a familial or rarely acquired disorder, is characterized biochemically by hypophosphatemia, decreased renal tubular reabsorption of phosphate, decreased intestinal absorption of calcium, and normal serum calcium. This report concerns a rare case of hypophosphatemic osteomalacia of unknown cause that was shown on Tc-99m MDP bone scanning.

Adult↗

Imaging of malignant lymphomas with F-18 FDG coincidence detection positron emission tomography.

PURPOSE: The authors evaluated the utility of F-18 fluorodeoxyglucose (FDG) coincidence detection (CoDe) positron emission tomography (PET) for staging, post-treatment evaluation, and follow-up assessment of patients with malignant lymphomas. MATERIALS AND METHODS: Fifty-eight patients with histologically proved malignant lymphomas (4 Hodgkin's disease, 54 non-Hodgkin's lymphoma) underwent CoDe PET using F-18 FDG. CoDe PET was performed using a dual-head gamma camera equipped with coincidence detection circuitry. Of the 87 CoDe PET studies, 26 were performed for staging, 38 for post-treatment evaluation, and 23 for follow-up evaluation of recurrence. The entire trunk, from the cervical to the inguinal regions, or selected regions were scanned with the patient in the supine position. No attenuation correction was made and reconstruction was performed using filtered back-projection rather than iterative reconstruction. CoDe PET findings were compared with corresponding results of computed tomographic (CT) and magnetic resonance imaging (MRI), tissue biopsy, or clinical follow-up. RESULTS: For staging, 52 sites were positive on CoDe PET or CT-MRI. CoDe PET detected 49 sites (94%), and CT-MRI showed 47 sites (90%). CoDe PET detected five more lymphomatous lesions and missed three lesions. For post-treatment evaluation, CoDe PET showed a positive predictive value of 100% and a negative predictive value of 83%, but the validated cases numbered only 11. For follow-up for recurrence, CoDe PET had a negative predictive value of 90%, but frequent false-positive findings were noted in the head and neck region as a result of underlying inflammatory changes. CONCLUSIONS: For staging, FDG CoDe PET alone without attenuation correction is not sensitive enough to be used as an independent imaging method, especially for small abdominal lesions. However, it appears to be an accurate method for assessing residual disease and for patient follow-up.

Adolescent↗

Clinical experience with ceramics in total hip replacement.

As part of a search for better articulation in total hip prostheses, the decrease in the thickness of the socket in different total hip prostheses was measured in vivo. The wear rates of (1) RCH 1000 (molecular weight, 10(6)) socket gamma-irradiated with 100 Mrad articulating with a crude COP (stainless steel containing 20% cobalt and 0.01% phosphorous) metal femoral head; (2) RCH 1000 socket nonirradiated articulating with a crude COP femoral head; (3) RCH 1000 socket irradiated with 100 Mrad articulating with an alumina femoral head; (4) ultra high molecular weight polyethylene (molecular weight, 5-6 x 10(6)) socket articulating with an alumina femoral head; and (5) ultrahigh molecular weight polyethylene socket articulating with a stainless steel femoral head (T-28) were 0.06, 0.30, 0.06, 0.1 and 0.25 mm/year, respectively, in the authors' clinical cases. Alumina femoral heads were effective in decreasing wear of the polyethylene socket. However, the wear rates of gamma-irradiated sockets articulating with alumina and with metal femoral heads wear very low and were not different from each other. Regarding the relationship between wear rate and the thickness of the ultra high molecular weight polyethylene socket articulating with a 28 mm alumina femoral head, on radiographs, average wear rates of socket thicknesses of 7, 8, 9, 10 and 11 mm were 0.14, 0.15, 0.12, 0.06, and 0.08 mm/year, respectively. On measuring retrieved prostheses, average wear rates of 7, 8, 9 and 11 mm thickness sockets were 0.2, 0.19, 0.14, and 0.1 mm/year, respectively. The wear of sockets has been proven to be minimal in alumina femoral heads articulating with ultrahigh molecular weight polyethylene sockets thicker than 10 mm.

Arthroplasty, Replacement, Hip↗

Anti-apoptotic action of hepatocyte growth factor through mitogen-activated protein kinase on human aortic endothelial cells.

OBJECTIVE: To investigate the molecular mechanisms of the anti-apoptotic action of hepatocyte growth factor (HGF), a novel angiogenic growth factor that may have a pivotal role in the regulation of endothelial cells, on human aortic endothelial cells. METHODS: An index of cell number and death was determined using a water-soluble tetrazolium salt dye assay, DNA fragmentation enzyme-linked immunosorbent assay, and non-confocal fluorescence microscopy of nuclear staining with Hoechst 33258 and propidium iodide. Extracellular-signal-regulated protein kinase (ERK) and the p38 mitogen-activated protein kinase (p38MAPK) were analysed by Western blotting using a phospho-specific antibody. RESULTS: Treatment of quiescent endothelial cells with HGF resulted in significant dose-dependent increases in cell numbers and decreases in lactate dehydrogenase (LDH) release. Moreover, HGF significantly attenuated endothelial cell death induced by culture in serum-free conditions. We therefore focused on the signal transduction system, and in particular on ERK and p38MAPK. ERK was markedly phosphorylated by HGF. The contribution of ERK to cell growth was supported by the observation that addition of PD98059, a specific inhibitor of MAPK kinase, significantly attenuated the increase in endothelial cell numbers induced by HGF, in a dose-dependent manner. Similarly, PD98059 also attenuated the decrease in LDH release and DNA fragmentation by HGF under serum-free conditions. Interestingly, ERK was re-phosphorylated at 12 h after stimulation. Re-phosphorylation of ERK was the result of induction of endogenous HGF by exogenously added HGF, as addition of neutralizing anti-HGF antibody to the conditioned medium attenuated re-phosphorylation of ERK at 12 h. In contrast, although p38MAPK was also phosphorylated by HGF, SB203580, a specific inhibitor of p38MAPK, failed to change the endothelial cell growth induced by HGF. CONCLUSION: We have demonstrated that the anti-apoptotic action of HGF against endothelial cell death was mainly through phosphorylation of ERK on human endothelial cells.

Aorta↗

Troglitazone inhibits mitogenic signaling by insulin in vascular smooth muscle cells.

Troglitazone (TRO) is an oral insulin-sensitizer that has direct effects on the vasculature to inhibit cell growth and migration. In vascular smooth muscle cells (VSMCs), insulin transduces a mitogenic signal that is dependent on the ERK1/2 MAP kinases. We examined the effects of TRO on this pathway and found that it inhibits mitogenic signaling. In quiescent VSMCs, insulin (1 microM) induced a 3.2-fold increase in DNA synthesis. TRO (1-20 microM) inhibited insulin-stimulated DNA synthesis by 72.8% at the maximal concentration. TRO at I and 10 microM had no significant effect on insulin-stimulated ERK1/2 activity. At 20 microM, however, TRO modestly enhanced insulin-stimulated ERK1/2 activity by 1.5-fold. ERKs transduce a mitogenic signal by phosphorylating transcription factors such as Elk-1. which regulate critical growth-response genes. We used GAL-Elk-1 expression plasmids to detect ERK-dependent activation of Elk-1. TRO at 1-20 microM potently inhibited insulin-stimulated, ERK1/2-dependent Elk-1 transcription factor activity. Neither early steps in insulin signaling nor the phosphatidylinositol 3-kinase (PI3K) branch of this pathway were affected by TRO, because it had no effect on IRS-1 phosphorylation, PI3K/IRS-1 association, or Akt phosphorylation. Because TRO is a known ligand for the nuclear transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma), we tested two other ligands for this receptor, rosiglitazone (RSG) and 15-deoxy-delta12,14 prostaglandin J2 (15d-PGJ2). Both also inhibited insulin-induced DNA synthesis. In summary, these data show that TRO inhibits mitogenic signaling by insulin at a point distal of ERK1/2 activation, potentially by a PPARgamma-mediated inhibition of ERK-dependent phosphorylation and activation of nuclear transcription factors that regulate cell growth.

Animals↗

Secondary correction of unsatisfactory blepharoplasty: removing multilaminated septal structures and grafting of preaponeurotic fat.

Oriental blepharoplasty, commonly known as a "double eyelid operation," is the most frequently practiced cosmetic procedure in Orientals, who have probably become more fold conscious because of social westernization and an influx of Caucasians into their society. Anatomically, the upper eyelids of an Oriental are considerably different from those of a white person, and nearly half of Orientals have single eyelids. When performing blepharoplasty, an appropriate design and operative technique must be carefully selected, taking into consideration the anatomical characteristics of Koreans to obtain an aesthetically pleasing result. However, the incidence of complications is high. Patients who are faced with unsatisfactory results are often perplexed by the fact that such a commonly performed procedure could have a very high rate of dissatisfaction and that an improvement is not easy. An unfavorable result need not imply a postoperative complication, but only that the result is not acceptable to the patient, whose goal may not be based on good aesthetic principles. The most common sources of dissatisfaction are postoperative asymmetry and high placement of the lid fold. From 1991 to 1998, secondary blepharoplasty was performed on 72 patients by slitting transversely, removing the multilaminated septal structures exposed to the previous operative scar, spreading the preaponeurotic fat that extruded, and removing the septal structures into a space where the scar was eliminated to prevent secondary adhesion. The average age of the patients was 26.5 years, and the average follow-up period was 2 years. No remarkable complication was encountered after operation with this method, and the desired aesthetic improvements were achieved in the majority of the patients.

Adolescent↗

Transactivation activity of the human cytomegalovirus IE2 protein occurs at steps subsequent to TATA box-binding protein recruitment.

The IE2 protein of human cytomegalovirus transactivates viral and cellular promoters through a wide variety of cis-elements, but the mechanism of its action has not been well characterized. Here, IE2-Sp1 synergy and IE2-TATA box-binding protein (TBP) interaction are examined by artificial recruitment of either Sp1 or TBP to the promoter. It was found that IE2 could cooperate with DNA-bound Sp1. A 117 amino acid glutamine-rich fragment of Sp1, which can interact with Drosophila TAF(II)110 and human TAF(II)130, was sufficient for the augmentation of IE2-driven transactivation. In binding assays in vitro, IE2 interacted directly with the C-terminal region of Sp1, which contains the zinc finger DNA-binding domain, but not with its transactivation domain, suggesting that synergy between IE2 and the transactivation domain of Sp1 might be mediated by other proteins such as TAF or TBP. It was also found that TBP recruitment to the promoter markedly increased IE2-mediated transactivation. Thus, IE2 acts synergistically with DNA-bound Sp1 and DNA-bound TBP. These results suggest that, in human cytomegalovirus IE2 transactivation, Sp1 functions at an early step such as recruitment of TBP and IE2 acts to accelerate rate-limiting steps after TBP recruitment.

Animals↗

Relationships between seizure severity and health-related quality of life in refractory localization-related epilepsy.

PURPOSE: To evaluate relationships between self-report measures of seizure severity and health-related quality of life (HRQOL) in people with refractory localization-related epilepsy. METHODS: A sample of 340 adults enrolled in a seven-center, prospective study of resective epilepsy surgery completed baseline questionnaires that included the Quality of Life in Epilepsy (QOLIE)-89 and a seven-item adaptation of the National Hospital Seizure Severity Scale. Associations between QOLIE-89 summary measures and both the total seizure severity scale score and individual seizure severity items were assessed, after adjustment for seizure frequency. RESULTS: The seizure severity measure had adequate scale score variability and reliability in this sample. Correlations between individual items in the scale did not exceed 0. 43. Product-moment partial correlations between the seizure severity scale and QOLIE-89 summary measures ranged from -0.17 to -0.29 (all p values <0.01). Of the seven seizure severity items, the average time before individuals perceived they were "really back to normal" after their seizures was broadly related to all domains of HRQOL (r values ranged from -0.16 to -0.30; p values <0.01). Severity of injury during seizures was the only other item having more than minimal associations with HRQOL, and it was selectively related to the physical health measure. Higher frequency of falls during seizures was modestly related to less employment. CONCLUSIONS: This seizure severity measure assesses constructs that are generally distinct from HRQOL, except for moderate and broad associations between HRQOL and patient's perceptions of the average duration of recovery time after seizures. Recovery time may potentially be a useful clinical indicator of seizure severity that reflects meaningful impairment of HRQOL in adults with frequent seizures.

Adolescent↗