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Biomedical subjects

M S Kim

Publications and source records attributed to M S Kim.

At least 91 records · Page 5Linked to original sources

Charge exchange ionization in collision cells as a method to detect the presence of long-lived excited electronic states of polyatomic ions.

Charge exchange ionization in collision cells installed in a double focusing mass spectrometer with reversed geometry has been used to detect the presence of a long-lived excited electronic state of benzene ion. In particular, the first collision cell located between the ion source and the magnetic sector was modified to serve as an ion source for the reagent ion generated by charge exchange with the primary ion. Strong reagent ion signals were observed when the ionization energies of the reagents (1,3-C4H6, CS2, CH3Cl) were lower than the recombination energy (approximately 11.5 eV) of the excited state benzene ion, while the signals were negligible for reagents (CH3F,CH4) with higher ionization energy. The fact that a strong signal is observable only for electronically exoergic charge exchange is useful for detecting the presence of a long-lived electronically excited state.

Journal Article↗

Simultaneous determination of multiple transcripts and splice variants of a primary transcript using ribonuclease protection assays.

The ribonuclease (RNase) protection assay (RPA) is an extremely sensitive technique used to determine specific mRNAs from cell and tissue extracts. The present protocol presents detailed procedures for a conventional RPA using antisense RNA probes purified with a Fullengther apparatus. The Fullengther has the advantage of being a relatively quick and safe procedure compared to more conventional methods for purification of full-length RNA probes. Using this protocol, we sought to simultaneously determine multiple mRNA species, including splice variants of the type I receptor (PAC(1)) of pituitary adenylate cyclase-activating polypeptide (PACAP), an important mediator in the regulation of luteinizing hormone-releasing hormone (LHRH) synthesis by ovarian steroids such as progesterone [7]. PAC(1) has more than eight splice variants. We have been able to discriminate the hop1 variant from other splice variants. To improve our understanding of the regulation mechanism of genes that are related to each other, such as LHRH and PACAP, it is most important to simultaneously determine genes that are involved in the same physiological areas of regulation. Using only 5 microg of total RNA sample from a single rat preoptic area, we simultaneously determined five different transcripts, including four rare mRNA species such as LHRH, PACAP, and hop1 variant and other splice variants of PAC(1), as well as the internal control of cyclophilin mRNA. This protocol provides a method for the simultaneous determination of multiple transcripts using the RPA.

Alternative Splicing↗

Synchronization of single motor units during voluntary contractions in the upper and lower extremities.

OBJECTIVE: To investigate motor unit synchronization in the time and frequency domains and compare the amount and nature of this synchronization between upper and lower extremity muscles in human subjects. METHODS: A total of 120 motor unit pairs from biceps brachii (BB), first dorsal interosseous (1DI), vastus medialis (VM), and tibialis anterior (TA) on the dominant side were analyzed and compared. Pairs of motor unit spike trains were recorded from two concentric needle electrodes inserted within these muscles in healthy volunteers. Subjects were instructed to maintain a weak isometric contraction of these muscles so that an individual motor unit recorded from each concentric needle discharged at a steady rate of approximately 10 impulses/s. Pairs of motor unit spike trains were cross-correlated in the time domain, and coherence analysis in the frequency domain was performed on the same spike train data. RESULTS: Synchronization was seen in all the muscles studied. Strength of motor unit synchronization, expressed as synchronization index (SI), was greater in 1DI muscles compared to other muscles (P<0.01). Coherence analysis revealed significant association between motor unit firings in the 1--5 and 25--30 Hz frequency ranges in all the muscles studied. The incidence of 25--30 Hz coherence peaks were found to be greater for 1DI muscles compared to other muscles. CONCLUSION: The above results suggest a possible role for corticospinal projections in producing pre-synaptic inputs responsible for synchronization of motor unit firings and 25--30 Hz coherence peaks.

Action Potentials↗

Sodium nitroprusside induces apoptosis of H9C2 cardiac muscle cells in a c-Jun N-terminal kinase-dependent manner.

Sodium nitroprusside (SNP) induces apoptosis in H9C2 cardiac muscle cells. Treatment with an exogenous NO donor SNP (2 mM) to H9C2 cells resulted in apoptotic morphological changes; a bright blue-fluorescent condensed nuclei and chromatin fragmentation by fluorescence microscope of Hoechst 33258-staining. The activity of caspase-3 like protease was increased during SNP-induced cell death. However, the activity of caspase-1 like protease was not affected by SNP. Pretreatment with Z-VAD-FMK (a pan-caspase inhibitor) or Ac-DEVD-CHO (a specific caspase-3 inhibitor) abrogated the SNP-induced cell death. SNP markedly activated three MAP kinases (JNK/SAPK, ERK and p38 MAP kinase) in the cardiac muscle cells. In this study, selective inhibition of the ERK or p38 MAPK pathway (by PD98059 or SB203580, respectively) had no effect on the extent of SNP-induced apoptosis in cardiac muscle cells. In contrast, inhibition of the JNK pathway by transfection of a dominant negative mutant of JNK markedly reduced the extent of SNP-induced cell death. Taken together, we suggest that JNK/SAPK will be related to SNP-induced apoptosis of H9C2 cardiac muscle cells.

Amino Acid Chloromethyl Ketones↗

Relationship between various surrogate indices of insulin resistance and mitochondrial DNA content in the peripheral blood of 18 healthy volunteers.

Mutations or deletions of mitochondrial DNA (mtDNA) are associated with diabetes mellitus. In this study, we investigated the relationships between the mtDNA content in peripheral blood and surrogate indices of insulin resistance in 18 healthy young women (mean age 20.8 +/- 1.5 years). The mtDNA content was significantly correlated with the area under the curve of insulin during an oral glucose tolerance test (r = -0.622), the homeostasis model assessment for insulin resistance (r = -0.616), the ratio of fasting glucose to insulin concentration (r = 0.586) and the fasting insulin level (r = -0.552). Further study is warranted to elucidate the mechanism by which the mtDNA content is associated with insulin resistance.

Journal Article↗

Intramedullary spinal cord astrocytoma in adults: postoperative outcome.

Intramedullary spinal cord astrocytomas are relatively rare and usually low-grade lesions with a long natural history. The rarity of the condition and its indolent clinical course has made the evaluation of treatment efficacy difficult. To clarify postoperative outcome and prognostic factors, we performed a retrospective analysis of intramedullary spinal cord astrocytomas in a single institute. Twenty-eight patients were surgically treated between 1978 and 1999; of median age 36 years (range, 19-68 years); nineteen patients were males and nine females. All patients presented with pain and neurological deficits. The cervical cord was involved in fifteen patients, cervico-thoracic in five, thoracic in six and thoraco-lumbar in two. Gross total removal was performed in three patients, subtotal removal in six, partial removal in fourteen and biopsy only in five. Nineteen patients received radiation therapy postoperatively. The mean follow-up period was 31.9 months (range, 0.5-184 months). Low-grade astrocytomas were found in 18 cases, anaplastic astrocytoma in three cases and glioblastomas in seven cases. The median survivals of patients with low- and high-grade astrocytoma were 184 months and 8 months, respectively (p < 0.05). The median survivals of irradiated and non-irradiated patients with low-grade astrocytoma were 184 months and 102 months. Neither the extent of resection, nor radiation influenced the survival rate. In summary, the histological grade was the most significant predictor of survival in patients with astrocytoma of the spinal cord.

Adult↗

Frontal P300 decrement and executive dysfunction in adolescents with conduct problems.

This study investigated the cognitive and cerebral function of adolescents with conduct problems by neuropsychological battery (STIM) and event-related potential (ERP). Eighteen adolescents with conduct disorder, and 18 age-matched normal subjects were included. Such cognitive functions as attention, memory, executive function and problem solving were evaluated using subtests of STIM. ERP was measured using an auditory oddball paradigm. The conduct group showed a significantly lower hit rate on the Wisconsin Card Sorting Test (WCST) than the control group. In addition, the conduct group showed reduced P300 amplitude at Fz and Cz, and prolonged P300 latency at Fz, and there was a significant correlation between P300 amplitude and Stroop test performance. These results indicate that adolescents with conduct problems have impairments of executive function and inhibition, and that these impairments are associated with frontal dysfunction.

Adolescent↗

Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes.

Low oxygen tension influences tumor progression by enhancing angiogenesis; and histone deacetylases (HDAC) are implicated in alteration of chromatin assembly and tumorigenesis. Here we show induction of HDAC under hypoxia and elucidate a role for HDAC in the regulation of hypoxia-induced angiogenesis. Overexpressed wild-type HDAC1 downregulated expression of p53 and von Hippel-Lindau tumor suppressor genes and stimulated angiogenesis of human endothelial cells. A specific HDAC inhibitor, trichostatin A (TSA), upregulated p53 and von Hippel-Lindau expression and downregulated hypoxia-inducible factor-1alpha and vascular endothelial growth factor. TSA also blocked angiogenesis in vitro and in vivo. TSA specifically inhibited hypoxia-induced angiogenesis in the Lewis lung carcinoma model. These results indicate that hypoxia enhances HDAC function and that HDAC is closely involved in angiogenesis through suppression of hypoxia-responsive tumor suppressor genes.

Animals↗

Radiofrequency energy delivery to the gastroesophageal junction for the treatment of GERD.

BACKGROUND: In this multi-center study, the feasibility, safety, and efficacy of radiofrequency (RF) energy delivery to the gastroesophageal junction (GEJ) for the treatment of gastroesophageal reflux disease (GERD) were investigated. METHODS: Forty-seven patients with classic symptoms of GERD (heartburn and/or regurgitation), a daily anti-secretory medication requirement, and at least partial symptom response to drugs were enrolled. All patients had pathologic esophageal acid exposure by 24-hour pH study, a 2 cm or smaller hiatal hernia, grade 2 or less esophagitis, and no significant dysmotility or dysphagia. RF energy was delivered with a catheter and thermocouple-controlled generator to create submucosal thermal lesions in the muscle of the GEJ. GERD symptoms and quality of life were assessed at 0, 1, 4, and 6 months with the short-form health survey (SF-36). Anti-secretory medications were withdrawn 7 days before each assessment of symptoms and pH/motility study. Medication use, endoscopic findings, esophageal acid exposure, and motility were assessed at 0 and 6 months. RESULTS: Thirty-two men and 15 women underwent treatment. At 6 months there were improvements in the median heartburn score (4 to 1, p < or = 0.0001), GERD score (26 to 7, p < or = 0.0001), satisfaction (1 to 4, p < or = 0.0001), mental SF-36 (46.2 to 55.5, p = 0.01), physical SF-36 (41.1 to 51.9, p < or = 0.0001), and esophageal acid exposure (11.7% to 4.8%, p < or = 0.0001). Esophagitis was present in 25 patients before treatment (15 grade 1 and 10 grade 2) and 8 had esophagitis at 6 months (4 grade 1 and 4 grade 2, p = 0.005). At 6 months, 87% no longer required proton pump inhibitor medication. There was no significant change in median lower esophageal sphincter pressure (14.0 to 12.0 mm Hg, p = 0.19), peristaltic amplitude (64 to 66 mm Hg, p = 0.71), or lower esophageal sphincter length (3.0 to 3.0, p = 0.28). There were 3 self-limited complications (fever for 24 hours, odynophagia lasting for 5 days, and a linear mucosal injury that was healed after 3 weeks). CONCLUSION: RF energy delivery significantly improved GERD symptoms, quality of life, and esophageal acid exposure while eliminating the need for anti-secretory medication in the majority of patients with a heterogeneous spectrum of clinical disease severity but with minimal active esophagitis or hiatal hernia.

Adult↗

Involvement of cyclic GMP in nitric-oxide-induced gastric relaxation Comparison of the actions of cyclic GMP and cyclic AMP.

BACKGROUND: Smooth muscle relaxation induced by various agents that increase the cellular levels of cyclic nucleotides (cAMP and cGMP) is accompanied by a decrease in intracellular Ca2+ concentration. However, little is known about the differences between the inhibitory effects of cAMP and cGMP on the contraction of smooth muscle. OBJECTIVE: To compare the effects and underlying mechanisms of cAMP and cGMP on the inhibition of gastric smooth muscle contraction, cyclic nucleotide promoting agents, as well as cell membrane permeable cyclic nucleotides were used. METHODS: Isometric contraction was measured from circular muscle strips prepared from the fundus of cat stomach in a cylinder-shaped chamber filled with Krebs-Ringer solution (pH 7.4, temperature 36 degrees C) bubbled with 5% CO2 in O2. The level of inositol phosphates (IPs) was measured. RESULTS: Forskolin and sodium nitroprusside significantly inhibited acetylcholine (ACh)-induced gastric smooth muscle contraction and increased the cellular levels of cAMP and cGMP, respectively. Direct application of 8-Br-cAMP and 8-Br-cGMP also significantly inhibited ACh-induced contraction. Both verapamil and TMB-8 inhibited ACh-induced contraction. The combined inhibitory effect of verapamil and TMB-8 was significantly greater than the effect of either one, separately. Forskolin or sodium nitroprusside similarly augmented the effect of verapamil. However, the inhibitory effect of TMB-8 was augmented only by 8-Br-cGMP or sodium nitroprusside but not by 8-BrcAMP or forskolin. Forskolin and 8-Br-cAMP significantly inhibited the formation of inositol phosphates stimulated by ACh. CONCLUSIONS: cAMP inhibits the contraction mechanism associated with intracellular Ca2+ mobilization as well as extracellular Ca2+ influx, while cGMP inhibits contraction by inhibiting the mechanism associated with extracellular Ca2+ influx.

Acetylcholine↗

Gamma-interferon (IFN-gamma) augments apoptotic response to mistletoe lectin-II via upregulation of Fas/Fas L expression and caspase activation in human myeloid U937 cells.

Mistletoe lectin-II, a major composition of Korean mistletoe (Viscum album coloratum), is known as a potent apoptosis inducer. The previous research has demonstrated that Korean mistletoe lectin-II induces apoptosis via c-Jun N terminal kinase (JNK) activation in human myeloid U937 cells. The purpose of this research is to prove the synergistic action of mistletoe lectin-II and interferon-gamma (IFN-gamma) in the apoptotic cytotoxicity of U937. When U937 cells were treated with mistletoe lectin-II after being differentiated by IFN-gamma, the proteolytic activity of caspase-3 and 9 was markedly elevated and that of caspase-8 was prolonged for 18 hr. The activation of caspase-3-like protease requires the earlier cleavage of poly(ADP-ribose) polymerase(PARP). Caspase-1 was, however, not activated during the resting phase and nor in IFN-gamma-differentiated U937 cells. Western blot analysis revealed that, in IFN-gamma-differentiated U937 cells, the expression of Fas (CD95/APO-1) & Fas ligand(FasL) increases the apoptotic sensitivity against Mistletoe lectin-II. Fas (CD95/APO-1) & FasL were not significantly induced solely by mistletoe lectin-II. Furthermore the activity of JNK1 in U937 cells was also markedly increased with IFN-gamma-differentiation, compared to that of the control. These results suggest that the IFN-gamma-differentiation of U937 cells increases the susceptibility to mistletoe lectin-II-induced apoptosis.

Apoptosis↗

Danchunhwan water extract prevents apoptotic death by peroxynitrite and nitric oxide in human dopaminergic neuroblastoma SH-SY5Y cells.

In the present study, the protective effects of Danchunhwan on the cytotoxicity by peroxynitrite and nitric oxide (NO) were investigated in human dopaminergic neuroblastoma SH-SYSY cells. Danchunhwan has been used to treat infarction and cerebrovascular diseases in Oriental medicine for centuries. Cells were pretreated with Danchunhwan and exposed to sodium nitroprusside (SNP), an NO donor, and 3-morpholinosydnonimine (SIN-1) which simultaneously generates NO and superoxide, thus possibly forming peroxynitrite. Exposure of cells to SIN-1 for 24 hr induced 75% of apoptotic cell death, as evaluated by ladder-pattern fragmentation of genomic DNA and characteristic of apoptosis using 4', 6-diamidino-2-phenylinol (DAPI). However, pretreatment of SH-SY5Y cells with Danchunhwan inhibited the apoptotic cell death in a dose-dependent manner. Even though Danchunhwan was washed out after preincubation for 12 hr, cells were still remained to be resistant against cytotoxicity of SIN-1. It also inhibited SIN-1-induced activation of caspase 3-like protease in a dose-dependent fashion. Furthermore, Danchunhwan recovered the levels of intracellular antioxidant system, reduced glutathione (GSH) (83%), which was decreased by the addition of SIN-1 (63%). Taken together, we suggest that Danchunhwan protects human neuroblastoma SH-SY5Y cells from apoptotic death by free radicals including peroxynitrite and NO via generation of antioxidant, GSH.

Antioxidants↗

Protective effects of Debo on zinc-induced apoptosis of C6 glial cells via modulation of intracellular antioxidant, reduced glutathione.

In the present study, the mechanical basis of a traditional herbal prescription, Debo. on cytotoxic damage of the brain cells including C6 glial and PC12 cells has been studied. Traditionally, Debo has been employed for the purpose of preventing responses to trauma, ischemia, and other diseases in the nervous system. C6 glial cells were exposed to oxidative stress through the imployment of ZnCl2, and generates H2O2 and hydroxyl radicals by fenton reaction. ZnCl2-induced death of C6 glial cells, which was revealed as apoptosis by chromatin condensation as well as DNA fragmentation. Pretreatment of Debo significantly prevented apoptotic death of C6 glial cells via inhibition of H2O, generation as well as the recovering of an antioxidant, reduced glutathione (GSH). Also, deprivation of serum and glucose, found in ischemia, deceased the viability of PC12 cells up to 60% via generation of H2O2. However, Debo significantly protected cells from ischemic damage through decrease in H2O, generation. Furthermore, Debo markedly inhibited the transcriptional activation of NF-kappaB by ZnCI, in C6 glial cells. These results suggest that Debo may function as an antioxidant system against free radicals and be applicable to protect brain cells against oxidative or ischemic stresses.

Animals↗

Estrogen regulates cytokine release in human mast cells.

Estrogens are important for bone homeostasis and are classified as anti-resorptive agents. In ovariectomized rats, mast cell changes occurred during the activation of resorption. In addition, quantitative changes occurred in mast cell population residing near the site undergoing resorption. Considering these studies, mast cells may play a role in osteoporosis. Therefore, it is of paramount importance to study mast cell cytokine production also in the presence or absence of estrogen. When cultured in the absence of estrogen, human mast cells treated with PMA or A23187 demonstrated significantly greater release of TNF-alpha and IL-6 than cells grown under estrogen-depleted condition. Our results show that treatment of mast cells with estrogen prevented PMA or A23187-stimulated TNF-alpha or IL-6 release. These data provide evidence for a potent inhibition of cytokines by estrogen in human mast cells. This study may help to explain the association between mast cells and osteoporosis.

Calcimycin↗

Neoplastic transformation and tumorigenesis associated with overexpression of phospholipase D isozymes in cultured murine fibroblasts.

Phospholipase D (PLD) has been suggested to play an important role in a variety of cellular functions. PLD activity has been shown to be significantly elevated in many tumours and transformed cells, suggesting the possibility that PLD might be involved in tumorigenesis. In this study, we have established stable cell lines overexpressing PLD1 and PLD2 from fibroblast cells. These cells, but not control cells, showed altered growth properties and anchorage-independent growth in soft agar. Both PLD1 and PLD2 also induced an up-regulation of the activity of matrix metalloprotease-9 as detected by zymograms. Furthermore, both PLD1 and PLD2 transformants, but not vector-transfectants, induced undifferentiated sarcoma when transplanted into nude mice. Both PLD1- and PLD2-mediated cell cycle distributions in stable cell lines revealed an increased fraction of cells in the S phase compared with control cells. Interestingly, the level of cyclin D3 protein, known as an activator of G(1) to S phase transition in the cell cycle, was aberrantly high in cells overexpressing PLD1 and PLD2 compared with control cells. These results suggest that overexpression of PLD isozymes may play an important role in neoplastic transformation.

Animals↗

The invertebrate odorant-binding protein LUSH is required for normal olfactory behavior in Drosophila.

The invertebrate odorant-binding proteins consist of a large family of low-molecular-weight, highly divergent proteins expressed exclusively in the chemosensory sensilla of insects. Each member of this family studied to date is secreted into the sensillum lymph of a small subset of sensilla by non-neuronal support cells. These expression patterns suggests an odor-specific function for these proteins as opposed to a general role in sensillum biology. Consistent with this notion, mutants defective for LUSH, a Drosophila member of this family, have odor-specific defects in olfactory behavior. The Drosophila genome contains at least 32 members of this gene family, rivaling the number of odorant receptors in this species. The relationship between these two protein families and how they act to determine odor specificity of olfactory neurons will be the topic of future studies.

Animals↗

The effect of intranasal fentanyl on the emergence characteristics after sevoflurane anesthesia in children undergoing surgery for bilateral myringotomy tube placement.

UNLABELLED: Children undergoing placement of bilateral myringotomy tubes (BMT) often exhibit pain-related behavior (agitation) in the postanesthesia care unit. We compared the emergence and recovery profiles of pediatric patients who received sevoflurane with or without supplementary intranasal fentanyl for BMT surgery. By using a prospective, double-blinded design, 150 children 6 mo to 5 yr of age, scheduled for routine BMT surgery, were anesthetized with sevoflurane (2%-3%) in a 60% N(2)O/O(2) gas mixture. Patients were randomized to receive equal volumes of intranasal saline (Control), 1 microg/kg fentanyl or 2 microg/kg fentanyl. A blinded observer evaluated each patient using a previously described 4-point agitation scale and the Steward recovery scale. Response to parental presence was observed after a score of six (full recovery) was achieved on the Steward recovery scale. There were no significant differences among the three groups regarding age, weight, surgeon, duration of anesthesia, or ear condition. Recovery times and emergence characteristic scores were not statistically different. Agitation scores were significantly reduced in the 2-microg/kg Fentanyl group as compared with the Control group (P = 0.012). Fentanyl 2 microg/kg is recommended to reduce the incidence of agitation seen in these patients. IMPLICATIONS: We examined the use of nasally administered fentanyl for the relief of agitation or discomfort after placement of bilateral myringotomy tubes in 150 children ages 6 mo to 5 yr using a prospective, double-blinded design. Fentanyl 2 microg/kg was found to reduce the incidence of agitation in these patients.

Administration, Intranasal↗

Distributional patterns of phospholipase C isozymes in rat pancreas.

Phospholipase C (PLC) isozymes are believed to play a role in regulating pancreatic exocrine and endocrine secretion. In an attempt to investigate the role of PLC, we examined the distribution patterns of PLC isozymes in the normal rat pancreas by Western blot analysis and immunohistochemistry. Western blot analysis was performed on pancreatic acinar tissues and the islet of Langerhans, which were separated from each other. PLC-beta isozymes (beta1, beta2, beta3, and beta4), delta1, and delta2 were detected in both acinar and islet cells, whereas PLC-gamma1 and gamma2 were observed only in acinar tissues. On immunohistochemistry, the immunoreactivities of PLC isozymes except for PLC-gamma1 were observed as follows: PLC-beta1, in both the exocrine and endocrine tissues; PLC-beta2, mainly in the periphery of the islet and acinar cells; PLC-beta3, in the periphery of the islet and in some ductal epithelium; PLC-beta4, through the islet of Langerhans and ductal epithelium; PLC-gamma1, not detected in pancreatic tissue; PLC-gamma2, mainly in acinar cells; PLC-delta1 and delta2, in the islet and in ductal epithelium. These results suggest that the intrapancreatic site-specific existence of PLC isozymes may modulate pancreatic exocrine and endocrine functions through a PLC-mediated signal transduction.

Animals↗