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Biomedical subjects

S H Kim

Publications and source records attributed to S H Kim.

At least 19 recordsLinked to original sources

The relationship between insulin resistance and dyslipidaemia in cigarette smokers.

AIM: Considerable evidence shows that cigarette smokers tend to have the dyslipidemic pattern of high plasma triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentrations, a highly atherogenic lipoprotein profile also typical of the insulin-resistant state even in the absence of cigarette smoking. However, because cigarette smokers are frequently insulin resistant, it is unclear if this dyslipidaemia is secondary to smoking, per se, or simply to the fact that smokers tend to be insulin resistant. The present study was initiated to determine whether this dyslipidaemia prevalent in cigarette smokers and characteristic of insulin-resistant individuals is a function of cigarette smoking or of insulin resistance. METHODS: As measured using vertical auto profile-II methodology, the lipid and lipoprotein concentrations were compared in 34 cigarette smokers divided into insulin-sensitive and insulin-resistant subgroups. The two groups were similar in age and body mass index, differing only in their insulin-mediated glucose uptake as quantified by the steady-state plasma glucose concentration determined during the insulin suppression test. RESULTS: While levels of TG and very low-density lipoprotein cholesterol (VLDL-C) were significantly elevated in insulin-resistant cigarette smokers, total cholesterol (C), low-density lipoprotein cholesterol (LDL-C), narrow-density (ND) LDL-C, intermediate-density lipoprotein-C (IDL-C), HDL-C and non-HDL-C were not different in the two groups. The insulin-resistant smokers also had a preponderance of small, dense LDL particles, while the reverse was true of the insulin-sensitive cigarette smokers. CONCLUSIONS: These data suggest that the dyslipidaemia previously attributed to smoking occurs primarily in those smokers who are also insulin resistant.

Adult↗

Expression of TGF-beta signaling proteins in normal placenta and gestational trophoblastic disease.

The transforming growth factor beta (TGF-beta) is a vital regulator of placental development and functions. TGF-beta exerts several modulatory effects on trophoblast cells, such as inhibition of proliferation and invasiveness, and stimulation of differentiation by inducing multinucleated cell formation. In this study, we determine the expression patterns of TGF-beta signaling molecules in normal trophoblast, various hydatidiform mole types and choriocarcinoma. A total of 132 cases, including 51 normal placenta (20 first trimester, 11 second trimester, and 20 third trimester) and 81 gestational trophoblastic diseases (17 choriocarcinoma, and 64 hydatidiform moles: 39 complete, 6 partial, and 19 invasive) were immunohistochemically analyzed with anti-TGF beta1/2, TGF-beta receptor type I (TbetaRI), TbetaRII, Smad 2/3, and Smad 4 antibodies on paraffin blocks. In the case of normal placenta, maximal levels of all TGF-beta signaling molecules were observed in villous trophoblast in the first trimester, which decreased with gestational age. Expression of all the TGF-beta signaling proteins except Smad2/3, was significantly enhanced in various moles, relative to normal trophoblast. Moreover, TGF-beta signaling molecules were significantly downregulated in choriocarcinoma, compared to moles. In particular, TbetaRI and Smad2/3 levels were lower in choriocarcinoma than normal villous trophoblast (TbetaRI: p<0.025, Smad2/3: p<0.001). In conclusion, the TGF-beta signaling pathway plays an important role in the pathogenesis and progression of gestational trophoblastic disease, and may thus be employed as a potential therapeutic target and a diagnostic biomarker.

Activin Receptors, Type I↗

Pinusolide and 15-methoxypinusolidic acid attenuate the neurotoxic effect of staurosporine in primary cultures of rat cortical cells.

BACKGROUND AND PURPOSE: Apoptosis is a fundamental process required for neuronal development but also occurs in most of the common neurodegenerative disorders. In an attempt to obtain an anti-apoptotic neuroprotective compound from natural products, we isolated the diterpenoids, pinusolide and 15-MPA, from B. orientalis and investigated their neuroprotective activity against staurosporine (STS) -induced neuronal apoptosis. In addition, we determined the anti-apoptotic mechanism of these compounds in rat cortical cells. EXPERIMENTAL APPROACH: Primary cultures of rat cortical cells injured by STS were used as an in vitro assay system. Cells were pretreated with pinusolide or 15-MPA before exposure to STS. Anti-apoptotic activities were evaluated by the measurement of cytoplasmic condensation and nuclear fragmentation. The levels of cellular peroxide, malondialdehyde (MDA) and [Ca(2+)]i, as well as the activities of superoxide dismutase (SOD) and caspase-3/7, were measured. KEY RESULTS: Pinusolide and 15-MPA, at a concentration of 5.0 ìM, reduced the condensed nuclei and rise in [Ca(2+)]i that accompanies apoptosis induced by 100 nM STS. Pinusolide and 15-MPA also protected the cellular activity of SOD, an antioxidative enzyme reduced by STS insult. Furthermore, the overproduction of reactive oxygen species and lipid peroxidation induced by STS was significantly reduced in pinusolide and 15-MPA treated cells. In addition, pinusolide and 15-MPA inhibited STS-induced caspase-3/7 activation. CONCLUSIONS AND IMPLICATIONS: These results show that pinusolide and 15-MPA protect neuronal cells from STS-induced apoptosis, probably by preventing the increase in [Ca(2+)]i and cellular oxidation caused by STS, and indicate that they could be used to treat neurodegenerative diseases.

Animals↗

Relationship between blood pressure parameters and pulse wave velocity in normotensive and hypertensive subjects: invasive study.

Blood pressure (BP) is one of the most important contributing factors to pulse wave velocity (PWV), a classic measure of arterial stiffness. Although there have been many non-invasive studies to show the relation between arterial stiffness and BP, the results are controversial. The aim of this study is to evaluate the role of BP as an influencing factor on PWV using invasive method. We observed 174 normotensive and untreated hypertensive subjects using coronary angiography. Arterial stiffness was assessed through aorto-femoral PWV by foot-to-foot velocity method using fluid-filled system. And BP was measured by pressure wave at the right common femoral artery. From univariate analysis, age, diabetes mellitus (DM), hypertension, waist, waist-to-hip ratio, total cholesterol-to-high-density lipoprotein cholesterol ratio, systolic BP (SBP), pulse pressure (PP) and mean arterial pressure (MAP) showed significant association with PWV. To avoid multiple colinearity among SBP, PP and MAP, we performed multiple regression analysis predicting PWV thrice. Age, DM and each BP were significantly and consistently correlated to PWV. In the first and third modules, compared to age, SBP and MAP were less strong predictors, respectively. However, PP was the stronger predictor than age and DM in the second module. Lastly, we simultaneously forced MAP and PP with other variables in the fourth multivariate analysis. Age, DM and PP remained significantly correlated with PWV, but the significance of MAP was lost. This is the first invasive study to suggest that PP has the strongest correlation with PWV among a variety of BP parameters.

Adult↗

Profiling signalling pathways of the receptor activator of NF-kappaB ligand-induced osteoclast formation in mouse monocyte cells, RAW264.7.

Cell-based signal chemical genomics can profile the signalling pathway for certain cellular events by using a target-known chemical library. To ascertain its usefulness, the receptor activator of NF-kappaB ligand (RANKL)-induced osteoclastogenesis in mouse monocyte/macrophage cells RAW264.7 was used as an in vitro experimental model. Of 180 target-known inhibitors/activators formatted in a 384-well plate, 8 chemicals were shown to inhibit the osteoclast formation, but 4 chemicals enhanced this process. A variety of references support, or possibly lead one to expect the effects of these 12 chemicals on the cellular process of osteoclastogenesis in RAW264.7 cells, but several signalling pathways were newly found in this study; for example, CA-074 Me inhibiting cathepsin B and nitrendipine blocking the calcium channel could have the potential to inhibit the osteoclast formation as well as bone resorption. This is a simple but very fast and powerful method of profiling the signalling pathway of certain cellular events. Signal chemical genomics could provide invaluable information for the exploration of new target signalling processes and further target-based drug discovery strategies.

Acid Phosphatase↗

Evaluation of developmental toxicity of amitraz in Sprague-Dawley rats.

This study investigated the potential adverse effects of amitraz on the initiation and maintenance of pregnancy in Sprague-Dawley rats as well as its effects on embryo-fetal development after maternal exposure during the entire pregnancy period. Amitraz was administered to pregnant rats by gavage from days 1 to 19 of gestation at dose levels of 0, 3, 10, and 30 mg/kg/day. All dams underwent a caesarean section on day 20 of gestation and their fetuses were examined for any external, visceral, and skeletal abnormalities. At 30 mg/kg, maternal toxicity manifested as an increase in the incidence of abnormal clinical signs and a lower body weight gain and food intake. Developmental toxicity included an increase in the fetal death rate, a decrease in the litter size, and a reduction in the fetal body weight. In addition, there was an increase in the incidence of fetal external, visceral, and skeletal abnormalities. At 10 mg/kg, maternal toxicity observed included a decrease in the body weight gain and a decrease in food intake. In addition, minimal developmental toxicity, including a decrease in the fetal body weight, an increase in the visceral and skeletal aberrations, and a delay in fetal ossification. There were no signs of either maternal toxicity or developmental toxicity at 3 mg/kg. These results show that amitraz administered during the entire pregnancy period in rats is embryotoxic and teratogenic at the maternally toxic dose (i.e., 30 mg/kg/day) and is minimally embryotoxic at a minimally maternally toxic dose (i.e., 10 mg/kg/day). Under these experimental conditions, the no-observed-adverse-effect level of amitraz for both dams and embryo-fetal development is estimated to be 3 mg/kg/day.

Abnormalities, Drug-Induced↗

Health-related quality of life in disease-free survivors of breast cancer with the general population.

BACKGROUND: Although most of the literature about health-related quality of life (HRQoL) focuses on breast cancer patients, few studies compared the HRQoL in disease-free breast cancer survivors with that of the general population. MATERIALS AND METHODS: We administered the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Quality of Life Questionnaire Breast Cancer Module, McGill Quality of Life Questionnaire, Beck Depression Inventory, and Brief Fatigue Inventory to 1933 disease-free survivors for over 1 year after being diagnosed with stage 0 to III breast cancer. We performed multivariate-adjusted analyses in all HRQoL comparisons. RESULTS: The scores for some health-related quality of life [corrected] HRQoL scales were comparable for both disease-free breast cancer survivors and the general female population, but [corrected] there was a [corrected] clinically significant difference between the two groups [corrected] in cognitive and social functioning, fatigue, insomnia, financial difficulties, body image, future perspective, breast symptoms, and arm symptoms. [corrected] CONCLUSIONS: Disease-free survivors of breast cancer had good HRQoL, which was less affected by the type of treatment than it was by demographic characteristics, time since surgery, comorbidity, fatigue, and depression.

Activities of Daily Living↗

Embolization of wide-necked aneurysms with using three or more microcatheters.

BACKGROUND: A new and relatively simple endovascular technique, in which more than three microcatheters are used for endovascular treatment of cerebral aneurysms for the first time, is described. METHOD: Eight patients with wide necked aneurysms were successfully treated with detachable coils using the multiple microcatheter technique. Three patients presented with subarachnoid haemorrhage and five were unruptured. The aneurysm locations were superior hypophyseal artery (2), posterior communicating artery (2), middle cerebral artery bifurcation (1), distal anterior cerebral artery (1), basilar artery (1) and vertebral artery (1). The average neck size was 7.4 +/- 2.8 mm (3.5-12 mm), average width of the aneurysms was 10.6 +/- 5.7 mm (6.2-23 mm) and depth was 8.9 +/- 5.8 mm (3-22 mm). Three microcatheters (7 patients) and four microcatheters (1 patient) were introduced and used for coil delivery. Three or four coils were deployed and intermingled to stabilize the whole coil mass as well as to occupy the aneurysmal sac. When a relatively stable coil frame was formed, one coil was detached and subsequent coils were inserted. After the coil mass became more stable, other coils were also detached and all microcatheters were used for subsequent coil deployment. FINDINGS: All aneurysms were successfully treated without complications. Postemboilzation angiograms showed no contrast filling in 5 cases (100% occlusion) and a very small residual neck in 3 cases. There was no procedure related complication. CONCLUSION: The multiple microcatheter technique can be one technical option for the endovascular treatment of wide necked aneurysms.

Adult↗

Prognostic factors and expression of p53 and mdm-2 in uterine sarcomas.

OBJECTIVES: To evaluate the clinicopathologic prognostic factors of uterine sarcoma, and determine whether overexpression of p53 and mdm-2 proteins correlate with overall survival and prognostic factors. METHODS: Thirty specimens from 43 patients with uterine sarcoma were available for slide review and evaluated by immunohistochemistry at Yonsei and Ajou University Medical Centers for the expression of p53 and mdm-2. RESULTS: Overall survival was found to correlate to histologic type of uterine sarcoma, surgical stage, tumor grade, and mitotic index. Whereas 63% of the sarcomas expressed p53, with a significant correlation to overall survival, 60% expressed mdm-2, with a significant correlation to the mitotic index but not to overall survival. CONCLUSION: Histologic type, surgical stage, tumor grade, mitotic index, and p53 expression were prognostic factors of the overall survival of patients with uterine sarcoma.

Adult↗

Early onset severe and late-onset mild Charcot-Marie-Tooth disease with mitofusin 2 (MFN2) mutations.

Mutations in the mitofusin 2 (MFN2) gene, which encodes a mitochondrial GTPase mitofusin protein, have recently been reported to cause both Charcot-Marie-Tooth 2A (CMT2A) and hereditary motor and sensory neuropathy VI (HMSN VI). It is well known that HMSN VI is an axonal CMT neuropathy with optic atrophy. However, the differences between CMT2A and HMSN VI with MFN2 mutations remained to be clarified. Therefore, we studied the phenotypic characteristics of CMT patients with MFN2 mutations. Mutations in MFN2 were screened in 62 unrelated axonal CMT neuropathy families. We calculated CMT neuropathy scores (CMTNSs) and functional disability scales (FDSs) to quantify disease severity. Twenty-one patients with the MFN2 mutations were studied by brain MRI. Ten pathogenic mutations were identified in 26 patients from 15 families (24.2%). Six of these mutations had not been reported, and de novo mutations were observed in five families (33.3%). The electrophysiological patterns of affected individuals with the MFN2 mutations were typical of axonal CMT; however, the clinical and electrophysiological characteristics were markedly different in early (<10 years) and late disease-onset (> or =10 years) groups. All patients with an early onset had severe CMTNS (> or =21) and FDS (6 or 7), whereas most patients with late onset had mild CMTNS (< or =10) and FDS (< or =3). We identified two HMSN VI families with the R364W mutation in the early onset group; however, two other families with the same mutation did not have optic atrophy. In addition, two early onset families with R94W mutations, previously reported for HMSN VI, did not have visual impairment. Interestingly, eight patients had periventricular and subcortical hyperintense lesions by brain MRI. In the late-onset group, three patients had sensorineural hearing loss and two had bilateral extensor plantar responses. We found that MFN2 mutations are the major cause of axonal CMT neuropathy, and that they are associated with variable CNS involvements. Phenotypes were significantly different in the early and late disease-onset groups. Our findings suggest that HMSN VI might be a variant of the early onset severe CMT2A phenotype.

Adolescent↗

Mutational analysis of the hCDC4 gene in gastric carcinomas.

hCDC4, a ubiquitin ligase, plays a role in the control of cell cycle and chromosome stability. The hCDC4 gene is considered a tumour suppressor gene and is mutated in several human neoplasias, including colorectal and endometrial tumours. Data on the hCDC4 mutation in gastric cancer is, however, lacking. This study explored the possibility that hCDC4 mutation is involved in the development of gastric cancer. The hCDC4 gene in 162 gastric adenocarcinoma tissues was analysed for somatic mutations using a polymerase chain reaction-single strand conformation polymorphism assay. Overall, six hCDC4 mutations were found (3.7%), comprising four missense, one frameshift deletion and one nonsense mutation(s). It is notable that the hCDC4 mutations were found in early as well as in advanced gastric carcinomas. These data indicate that hCDC4 mutation occasionally occurs in gastric carcinomas and suggest that it might play a role in the development of some gastric carcinomas.

Aged↗

Clinical and radiological results following cervical arthroplasty.

BACKGROUND: This was a retrospective study of clinical and radiological results of cervical arthroplasty using the Bryan cervical disc prosthesis to evaluate the efficacy of arthroplasty in clinical applications. METHODS: A total of 46 patients underwent arthroplasty of a single level using the Bryan disc prosthesis. Clinical outcome was assessed using the visual analogue scale (VAS) and the neck disability index (NDI). All patients were evaluated using preoperative and postoperative static cervical spine radiographs to compare cervical sagittal balance. Dynamic cervical spine radiographs were used to compare movement at the level of the procedure, movement at the adjacent level and movement of the whole cervical spine. FINDINGS: With the exception of four patients with aggravated neck pain, the NDI and VAS scores decreased significantly in late follow-up evaluations. The range of movement of the whole cervical spine, the functional segmental unit, and the adjacent segments were preserved after arthroplasty. The sagittal alignment of the cervical spine showed kyphosis after surgery but restored lordosis at a later time. The postulated cause of kyphotic changes include "over-milling" at the dorsal endplate, inappropriate angle of disc insertion, structural absence of lordosis in the Bryan disc, removal of posterior longitudinal ligament, and pre-existing kyphosis. CONCLUSIONS: Arthroplasty using the Bryan disc appears to be safe and provided a favorable preliminary clinical and radiological outcome. Postoperative kyphosis can be prevented by understanding the biomechanical properties of the Bryan disc. Future studies will need to address the association between postoperative kyphosis, clinical outcome and adjacent segment disease.

Adult↗

An orally active cathepsin K inhibitor, furan-2-carboxylic acid, 1-{1-[4-fluoro-2-(2-oxo-pyrrolidin-1-yl)-phenyl]-3-oxo-piperidin-4-ylcarbamoyl}-cyclohexyl)-amide (OST-4077), inhibits osteoclast activity in vitro and bone loss in ovariectomized rats.

Human cathepsin K, a cysteine proteinase of the papain family, has been recognized as a potential drug target for the treatment of osteoporosis. The predominant expression of cathepsin K in osteoclasts has rendered the enzyme into a major target for the development of novel antiresorptive drugs. Now, we report the pharmacological properties of OST-4077 [furan-2-carboxylic acid (1-{1-[4-fluoro-2-(2-oxo-pyrrolidin-1-yl)-phenyl]-3-oxo-piperidin-4-ylcarbamoyl}-cyclohexyl)-amide] as a novel selective cathepsin K inhibitor. Human and rat cathepsin K were inhibited in vitro by OST-4077 with the IC50 values of 11 and 427 nM, respectively. OST-4077 suppressed bone resorption induced by rabbit osteoclasts (IC50, 37 nM) but did not affect bone mineralization or cellular alkaline phosphatase activity in MC3T3-E1 cells. Parathyroid hormone-induced bone resorption was inhibited in a dose-dependent manner in thyroparathyroidectomized rats gavaged with a single dose of OST-4077 (ED50, 69 mg/kg). When given orally twice daily for 4 weeks to 3-month-old ovariectomized (OVX) rats, OST-4077 dose-dependently prevented bone loss, as monitored by bone densitometry, ash content, and urinary excretion of deoxypyridinoline. No change in serum osteocalcin in the OVX rats by OST-4077 suggested that bone formation might not be affected by the agent. In summary, OST-4077 selectively inhibited bone resorbing activities of osteoclasts and prevented bone loss induced by estrogen deficiency but did not affect bone formation. OST-4077, an orally active selective human cathepsin K inhibitor, may have the therapeutic potential for the treatment of diseases characterized by excessive bone loss including osteoporosis.

Alkaline Phosphatase↗

Laparoscopic colorectal surgery using low-pressure pneumoperitoneum combined with abdominal wall lift by placement of anchoring sutures around the camera port.

BACKGROUND: This study aimed to evaluate the feasibility of low-pressure pneumoperitoneum in laparoscopic colorectal surgery. METHODS: The authors designed low-pressure (8 mmHg) laparoscopy combined with abdominal wall lift simply by placement of anchoring sutures around the camera port. RESULTS: The operative indications were 176 colon cancers, 297 rectal cancers, and 45 benign diseases. The average blood loss was 92 ml (range, 20-1200 ml), and the mean operating time was 204 min (range, 23-525 min). Conversion to an open procedure was required in eight cases (1.5%). Two patients experienced intraoperative complications. The mean number of removed lymph nodes was 28.9 in the colon cancer cases and 23.1 in the rectal cancer cases. The mean length of resected specimen was 27.3 cm (range, 8.5-136 cm). Postoperatively, cardiopulmonary complications developed in five patients (0.9%). CONCLUSIONS: Abdominal wall lifting by anchoring sutures around the camera port in addition to low-pressure pneumoperitoneum is a simple, safe, and effective method for laparoscopic colorectal procedure.

Abdominal Wall↗

Spinal metastasis from cranial meningeal hemangiopericytomas.

Spine metastasis from cranial meningeal hemangiopericytomas are extremely rare, with five surgically verified cases. We describe a case of a 55-year-old female diagnosed with metastatic hemangiopericytoma to the cervical spine 78 months after the first operation. Because of the long latency period, aggressive spinal surveillance should be advocated along with repeated bone scintigraphy and MRI.

Cervical Vertebrae↗

In-flight kinetic measurements of the aerosol growth of carbon nanotubes by electrical mobility classification.

We describe an on-the-fly kinetic study of gas-phase growth of multiwalled carbon nanotubes. The methodology employs electrical mobility classification of the CNT, which enables a direct measure of CNT length distribution in an aerosol reactor. The specific experiment employs two mobility classification steps. In the first step we mobility classify the catalyst particle, in this case Ni, created by pulsed laser ablation, to generate a stream of monodisperse particles. This then determined the diameter of the CNT, when a hydrocarbon/H2 mix is added in a heated aerosol reactor. A second electrical mobility classification step allows us to determine the length distribution of the CNTs. We found that CNT growth from ethylene required the addition of small amounts of water vapor, whereas growth from acetylene did not. We show that acetylene, which always has small amounts of acetone present when purchased, can provide the oxygen source to prevent catalyst coking. By varying the temperature of the growth, we were able to extract Arrhenius growth parameters. We found an activation energy for growth approximately 80 kJ mol(-1) from both acetylene and ethylene, which is considerably lower than previous works for substrate-grown CNTs (E(a) = 110-150 kJ mol(-1)). Furthermore, we observed that our aerosol CNT growth rates were about 2 orders of magnitude higher than those for substrate-grown CNTs. The dominant growth mechanism of CNT previously proposed is based upon bulk diffusion of carbon through nickel particles. However, on the basis of the lower activation energy found in this work, we proposed that the possible mechanism of gas-phase growth of CNT is correlated with both surface (E(a) = 29 kJ mol(-1)) and bulk diffusion (E(a) = 145 kJ mol(-1)) of carbon on nickel aerosol particles. Finally, the experimental approach described in this work should be amenable to other nanowire systems grown in the aerosol phase.

Journal Article↗

Spinal extradural arachnoid cyst.

Spinal extradural arachnoid cysts are rare expanding lesions in the spinal canal. They usually present with progressive signs and symptoms caused by spinal cord compression if they enlarge. A comprehensive review about spinal extradural arachnoid cyst is made including the author's own case of a 59-year-old woman with a 6-month history of progressive back pain radiating to both legs. Key points concerning the possible pathogenesis including symptomatology, diagnosis, and the implications for treatment are highlighted. Surgical treatment is curative and this rare clinical entity should be considered in the differential diagnosis of spinal extradural lesions.

Arachnoid Cysts↗

Clipping vs coiling of posterior communicating artery aneurysms with third nerve palsy.

The authors investigated the evolution of third nerve palsy in patients with posterior communicating artery aneurysms who underwent coiling vs clipping. There was no statistical difference of complete third nerve palsy recovery in both treatments. Both techniques were of clinical benefit. Older age, diabetes, delayed interventions, and complete third nerve palsy at presentation indicated a poor prognosis for recovery.

Adult↗