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Biomedical subjects

M S Kim

Publications and source records attributed to M S Kim.

At least 73 records · Page 4Linked to original sources

Actions of cocaine- and amphetamine-regulated transcript (CART) peptide on regulation of appetite and hypothalamo-pituitary axes in vitro and in vivo in male rats.

Cocaine- and amphetamine-regulated transcript (CART) and CART peptide are abundant in hypothalamic nuclei controlling anterior pituitary function. Intracerebroventricular (ICV) injection of CART peptide results in neuronal activation in the paraventricular nucleus (PVN), rich in corticotrophin-releasing factor (CRH) and thyrotrophin-releasing factor (TRH) immunoreactive neurons. The aims of this study were three-fold. Firstly, to examine the effects of CART peptide on hypothalamic releasing factors in vitro, secondly, to examine the effect of ICV injection of CART peptide on plasma pituitary hormones and finally to examine the effect of PVN injection of CART peptide on food intake and circulating pituitary hormones. CART(55-102) (100 nM) peptide significantly stimulated the release of CRH, TRH and neuropeptide Y from hypothalamic explants but significantly reduced alpha melanocyte stimulating hormone release in vitro. Following ICV injection of 0.2 nmol CART(55-102), a dose which significantly reduces food intake, plasma prolactin (PRL), growth hormone (GH) and adrenocorticotrophin hormone (ACTH) and corticosterone increased significantly. Following PVN injection of CART(55-102), food intake was significantly reduced only at 0.2 and 0.6 nmol. However, PVN injection of 0.02 nmol CART(55-102) produced a significant increase in plasma ACTH. ICV injection of CART peptide significantly reduces food intake. Unlike many anorexigenic peptides, there is no increased sensitivity to PVN injection of CART(55-102). In contrast, both ICV and PVN injection of CART(55-102) significantly increased plasma ACTH and release of hypothalamic CRH is significantly increased by CART peptide in vitro. This suggests that CART peptide may play a role in the control of pituitary function and in particular the hypothalamo-pituitary adrenal axis.

Animals↗

Impaired alpha-interferon signaling in transitional cell carcinoma: lack of p48 expression in 5637 cells.

The limited success of IFN-alpha therapy for clinical treatment of transitional cell carcinoma (TCC) has prompted us to investigate the responsiveness of TCC lines to IFN-alpha. The response to IFN-alpha in terms of 561 gene induction, an IFN-stimulated response element-containing IFN-alpha/beta-inducible gene, and IFN-stimulated gene factor 3 (ISGF3) formation was normal in primary human urothelial cells. We tested the antiproliferative effects of IFN-alpha in three TCC lines as a measure of IFN-alpha responsiveness, and variable patterns of growth inhibition were observed in three TCC lines. More than 90% growth inhibition was noted in TCCSUP cells, whereas only 40% and 10% inhibition by IFN-alpha was observed in 5637 and HT1197 cells, respectively. IFN-alpha treatment formed extremely low levels of ISGF3 in electrophoretic mobility shift assays in these later two relatively insensitive cells. In addition, expression of the 561 gene was significantly reduced in these two TCC lines by Northern blots. We have further identified a low expression level of Tyk2 in HT1197 cells compared with two other TCCs. This suggests that an extremely low ISGF3 level after IFN-alpha treatment may be due to low Tyk2 expression or other unidentified defects. In 5637 cells, p48 protein expression was undetectable. This undetectable p48 expression is not due to a deletion in the coding region because the correct size protein is detected following IFN-gamma treatment. Consequently, the ISGF3 complex formation and 561 gene induction were restored by IFN-gamma pretreatment plus IFN-alpha treatment. Introduction of p48 expressing plasmid into 5637 cells was sufficient to form the ISGF3 complex by IFN-alpha treatment, suggesting the defect lies in the expression of p48 protein in 5637 cells. Detailed mechanistic understanding of the action of IFNs in bladder cancer cell lines may explain the abrogated therapeutic response of IFN-alpha in the clinical treatment of TCCs.

Carcinoma, Transitional Cell↗

The involvement of phospholipase A(2) in ethanol-induced gastric muscle contraction.

To understand the underlying mechanism of ethanol in tonic contraction, the effect of ethanol on phospholipase A(2) and phospholipase C activities and the effects of phospholipase inhibitors on ethanol-induced contraction of cat gastric smooth muscle were tested. Circular muscle strips (2.0 x 0.2 cm) obtained from the fundus of cat stomach were used to measure isometric contraction. Ethanol elicited tonic contraction and activated phospholipase A(2) activity in a dose-dependent manner. Phospholipase A(2) inhibitors, manoalide (0.1--10 microM) and oleyloxyethyl phosphorylcholine (1--10 microM), significantly inhibited ethanol-induced contraction. Furthermore, 342 mM ethanol-induced contraction was significantly inhibited by cyclooxygenase inhibitors, ibuprofen (10--100 microM) and indomethacin (10--100 microM), but not by lipoxygenase inhibitors. On the other hand, phospholipase C inhibitors had no effect on ethanol-induced contraction, indicating that phospholipase C is not involved in ethanol-induced contraction. It is suggested from the above results that ethanol-induced contraction in cat gastric smooth muscle is, in part, mediated by phospholipase A(2) and cyclooxygenase pathways.

Animals↗

TBX5 transcription factor regulates cell proliferation during cardiogenesis.

Mutations in human TBX5, a member of the T-box transcription factor gene family, cause congenital cardiac septation defects and isomerism in autosomal dominant Holt-Oram syndrome. To determine the cellular function of TBX5 in cardiogenesis, we overexpressed wild-type and mutant human TBX5 isoforms in vitro and in vivo. TBX5 inhibited cell proliferation of D17 canine osteosarcoma cells and MEQC quail cardiomyocyte-like cells in vitro. Mutagenesis of the 5' end of the T-box but not the 3' end of the T-box abolished this effect. Overexpression of TBX5 in embryonic chick hearts showed that TBX5 inhibits myocardial growth and trabeculation. TBX5 effects in vivo were abolished by Gly80Arg missense mutation of the 5' end of the T-box. PCNA analysis in transgenic chick hearts revealed that TBX5 overexpression does suppress embryonic cardiomyocyte proliferation in vivo. Inhibitory effects of TBX5 on cardiomyocyte proliferation include a noncell autonomous process in vitro and in vivo. TBX5 inhibited proliferation of both nontransgenic cells cocultured with transgenic cells in vitro and nontransgenic cardiomyocytes in transgenic chick hearts with mosaic expression of TBX5 in vivo. Immunohistochemical studies of human embryonic tissues, including hearts, also demonstrated that TBX5 expression is inversely related to cellular proliferation. We propose that TBX5 can act as a cellular arrest signal during vertebrate cardiogenesis and thereby participate in modulation of cardiac growth and development.

Amino Acid Substitution↗

Live donor renal allograft in end-stage renal failure patients from immunoglobulin A nephropathy.

BACKGROUND: The purpose of this study was to attempt to resolve two important issues, i.e. to determine (1) whether the course of recurrent immunoglobulin A nephropathy (IgAN) is benign, and (2) whether it is advisable to use a related donor. METHODS: We evaluated the long-term outcome, in terms of recurrence and graft survival, after live related or unrelated donor renal transplantation, and assessed the validity of the use of related donors in 90 grafts in 89 IgAN patients. RESULTS: Ten-year graft survival for IgAN patients was 66%, compared with 84% for 107 reference recipients who had other kinds of glomerulonephritis (GN), and with 69% in 90 other recipients who had non-GN renal failure (P=0.27). In 43 grafts, 54 event graft biopsies were performed, documenting the presence of mesangial IgA deposits in 19 of those grafts. In eight grafts, lesions were accompanied by chronic rejection (CR). Ten-year cumulative recurrence was 44%. Ten grafts were lost: by CR (n=3) or acute rejection (n=1) in 24 recurrence-free recipients, by CR (n=2) or recurrence (n=2) in 19 recurrent patients, and by patient death (n=2) in 46 patients devoid of graft biopsy. We found no difference in 10-year graft survival between the recurrent and recurrence-free patients (63% vs. 74%, P=0.98), or the proportion of related donors (68% vs. 83%, P=0.25). The presence or matching of HLA B12, B35, or DR4 did not affect the recurrence. CONCLUSIONS: Recurrence increased to 44% with longer follow-up, but this did not limit the graft outcome. Recurrence was not affected by the kind of live donor. We conclude that live related or unrelated kidneys should be offered to IgAN patients.

Adult↗

Cloning and characterization of tissue inhibitor of metalloproteinase-3 (TIMP-3) from shark, Scyliorhinus torazame.

We cloned the full-length cDNA encoding TIMP-3 from the cartilage of cloudy dogfish, Scyliorhinus torazame. The entire open reading frame was composed of 645 nucleotides and 214 residues including 12 conserved cysteines and asparagine-184, a putative site for N-linked sugars. It showed about 72% identity to those of other species based on the deduced amino acid sequence. The mRNA of shark TIMP-3 were expressed abundantly in brain and cartilage tissues. To investigate the roles of shark TIMP-3, an expression vector was constructed and transfected into HT1080 human fibrosarcoma cells. Overexpression of shark TIMP-3 reduced the activity of MMP-2 in gelatin zymography. Through human Alu PCR based CAM assay, we also confirmed that shark TIMP-3 transfected HT1080 cells had less intravasation effects.

Amino Acid Sequence↗

Inhibition of invasion and induction of apoptosis by curcumin in H-ras-transformed MCF10A human breast epithelial cells.

Curcumin, a dietary pigment in turmeric, posseses anti-carcinogenic and anti-metastatic properties. The present study was conducted to study in vitro chemopreventive effects of curcumin in transformed breast cells. Here, we show that curcumin inhibits H-ras-induced invasive phenotype in MCF10A human breast epithelial cells (H-ras MCF10A) and downregulates matrix metalloproteinase (MMP)-2 dose-dependently. Curcumin exerted cytotoxic effect on H-ras MCF10A cells in a concentration-dependent manner. Curcumin-induced cell death was mainly due to apoptosis in which a prominent downregulation of Bcl-2 and upregulation of Bax were involved. We also suggest a possible involvement of caspase-3 in curcumin-induced apoptosis. Curcumin treatment resulted in the production of reactive oxygen species (ROS) in H-ras MCF10A cells. Apoptotic event by curcumin was significantly inhibited by pretreatment of an antioxidant N-acetyl-L-cysteine (NAC), suggesting redox signaling as a mechanism responsible for curcumin-induced apoptosis in H-ras MCF10A cells. Taken together, our results demonstrate that curcumin inhibits invasion and induces apoptosis, proving the chemopreventive potential of curcumin.

Antineoplastic Agents, Phytogenic↗

Growth-inhibitory effect of adenovirus-mediated p53 gene transfer on medulloblastoma cell line, Daoy, harboring mutant p53.

To improve the survival rate, gene therapy, such as the replacement of inactivated tumor suppressor genes, has become a new investigational adjuvant treatment modality for human malignancies. We investigated the effect of adenovirus(Ad)-mediated transfer of wildtype p53 tumor suppressor gene on the medulloblastoma cell line, Daoy, which harbors mutant-type p53 gene. At 50 multiplicity of infection (moi), immunohistochemical staining with p53 monoclonal antibody showed positive staining in all cells 2 days after Ad-CMV-p53 infection. The high expression of wild-type p53 protein was detected in Ad-CMV-p53-infected cells, and expression of wild-type p53 protein peaked on day 2 after the infection. The growth of Ad-CMV-p53-infected cells was greatly suppressed in vitro, and the Ad-CMV-p53 treatment significantly reduced the tumor mass in vivo. The mean weight of Ad-CMV- infected tumors was only 16% of those which were mock infected, and 25% of those which were Ad-CMV-beta-gal infected. On microscopic examination, Ad-CMV-p53-infected tumors showed numerous apoptotic bodies. This Ad-CMV-p53 gene transfer showed high transduction efficacy and expression, resulting in significant growth inhibition of Daoy harboring mutant type p53.

Adenoviruses, Human↗

Hyperbaric oxygenation pretreatment induces catalase and reduces infarct size in ischemic rat myocardium.

Ischemia-reperfusion injury is a major complication occurring in heart stroke, cardiopulmonary bypass surgeries, and heart transplantation. Reactive oxygen species generated during the reperfusion phase overwhelm the scavenging capacities of antioxidant enzymes, and result in oxidative damage to the myocardium. We examined whether hyperbaric oxygenation (HBO) pretreatment induces antioxidant enzymes and protects the heart from subsequent ischemia-reperfusion injury. Rats were intermittently exposed to 100% O2 at 3 ATA (where ATA is absolute atmosphere) for 1 h daily and then sacrificed after 24 h of recovery in room air. Isolated hearts were subjected to 40 min of ischemia and 90 min of reperfusion. HBO pretreatment was found to condition the heart and enhance enzymatic activity and gene expression of catalase, thereby significantly reducing infarct size after reperfusion. A catalase inhibitor, 3-amino-1,2,4-triazole, completely abolished the infarct-limiting effect of HBO pretreatment, which suggests that HBO-induced tolerance against ischemia-reperfusion injury is due to catalase induction. Our results imply that HBO preconditioning may be developed as a new preventive measure for reperfusion injury in the heart.

Amitrole↗

Long-term results of kidney transplantation between HLA-identical siblings.

Long-term data on HLA-identical renal transplants are scarce, and the advantages of using cyclosporine (CsA) over azathioprine (AZA) have yet to be elucidated. In 68 recipients from HLA-identical donors (37 under AZA-steroids and 31 under CsA-steroids), we estimated the graft and patient survival to posttransplant 120 months, and compared the results between patients on different protocols. Episodes of rejection, causes of graft loss or patient death, and longterm complications were also compared retrospectively. The 10-year patient/graft survivals were comparable: 82.7/67.6% for the AZA and 78.4/63.5% for the CsA patients. The incidence of acute rejection during the first year after transplant was also comparable. We lost 25 grafts. The major causes of graft loss were patient death (7/13 in AZA and 5/12 in CsA patients) and chronic rejection (3/13 in AZA and 3/12 in CsA patients). Four grafts were lost due to poor compliance. We lost 12 patients due mostly to cerebrovascular disease and infections. There was no difference in the prevalence of complications between patients. In conclusion, the long-term outcome was excellent in this subgroup of transplant patients. We could not find any advantages of using CsA over AZA in these patients after a long-term follow-up. To achieve better results, continued attention should be paid to the prevention of poor compliance and complications.

Adult↗

Acanthopanax senticosus root inhibits mast cell-dependent anaphylaxis.

BACKGROUND: Mast cells synthesize and secrete chemical mediators which play a central role in anaphylaxis. METHODS: The effect of Acanthopanax senticosus root (ASR) on mast cell-dependent anaphylaxis was investigated. RESULTS: ASR inhibited compound 48/80-induced systemic anaphylactic shock at the dose of 1.0 g/kg by 50%. When ASR was given as pre-treatment at concentrations ranging from 0.01 to 2.0 g/l, the histamine release from rat peritoneal mast cells induced by compound 48/80 was reduced in a dose-dependent manner. ASR (2.0 g/kg) also inhibited passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE to 53.17+/-6.62%. Moreover, ASR inhibited tumor necrosis factor-alpha production in a concentration-dependent manner, and the treatment of 1 g/l blocked the production by 32.5+/-3.50% compared to saline value. CONCLUSIONS: ASR may possess effective anti-anaphylactic activity.

Anaphylaxis↗

Correlation of plasma homocysteine and mitochondrial DNA content in peripheral blood in healthy women.

Hyperhomocysteinemia is an independent risk factor of cardiovascular disease and associated with insulin resistance, although their causal relationship remains unclear. A previous report has shown that high concentration of homocysteine damages mitochondrial gene expression, function and structure. As we found recently, the mitochondrial DNA (mtDNA) contents are inversely correlated with insulin resistance parameters. Thus there is possibility that plasma total homocysteine (tHcy) level is somewhat correlated with mtDNA content. Sixty healthy women (mean age 40.3+/-20.9 yr, range 18-78 yr) were recruited to investigate the correlation of plasma tHcy level and mtDNA content in peripheral blood. A significant negative correlation was found between plasma tHcy levels and mtDNA content (r=-0.507, P<0.01). Plasma tHcy and mtDNA content have an independent effect on each other and on insulin resistance (HOMA-insulin resistance (IR) score) respectively in multiple regression model. Plasma tHcy showed positive correlations with age (r=0.407), W/H ratio (r=0.370), total cholesterol (r=0.338), LDL-cholesterol (r=0.317) and insulin resistance (HOMA-IR score) (r=0.261); and a negative correlation with folate (r=-0.273). MtDNA content showed negative correlations with age (r=-0.407), BMI (r=-0.440), W/H ratio (r=-0.659), SBP (r=-0.350), total cholesterol (r=-0.340), triglyceride (r=-0.376), LDL-cholesterol (r=-0.349), fasting plasma insulin (r=-0.483), and insulin resistance (HOMA-IR score) (r=-0.423); and a positive correlation with folate (r=0.299). In this study, there was a significant inverse correlation between plasma tHcy level and mtDNA content. Further study will be warranted to elucidate the mechanism by which two factors are associated.

Adolescent↗

Expression and regulation of phospholipase D during neuronal differentiation of PC12 cells.

To assess a possible role for phospholipase D (PLD) in PC12 cell signal transduction and differentiation, we have investigated the expression of PLD in PC12 cells and found that the differentiation factor, nerve growth factor (NGF) increased PLD1 protein expression and phorbol 12-myristate 13 acetate (PMA)-induced PLD activity. During neuronal differentiation, this effect showed correlation to the protein expression levels of classical protein kinase C (PKC) isozymes, PKC-alpha and -beta II, but there was no significant increase in the protein level of RhoA, another regulatory factor for PLD activation. Interestingly, PLD1 was associated with PKC-alpha or beta II, and its association gradually increased as NGF-induced neuronal differentiation progressed. PKC inhibitor, Ro-31-8220, caused a significant inhibition of neurite outgrowth and PLD activity. Furthermore, PLD1 was constitutively associated with the Shc adaptor molecule, the overexpression of which is known to induce PLD activity and to induce neurite outgrowth. Taken together, the data in this study suggests that PLD1 is closely implicated in neuronal differentiation of PC12 cells.

Amino Acid Sequence↗

Effects of norfluoxetine, the major metabolite of fluoxetine, on the cloned neuronal potassium channel Kv3.1.

The effects of fluoxetine and its major metabolite, norfluoxetine, were studied using the patch-clamp technique on the cloned neuronal rat K(+) channel Kv3.1, expressed in Chinese hamster ovary cells. In whole-cell recordings, fluoxetine and norfluoxetine inhibited Kv3.1 currents in a reversible concentration-dependent manner, with an IC(50) value and a Hill coefficient of 13.11+/-0.91 microM and 1.33+/-0.08 for fluoxetine and 0.80+/-0.06 microM and 1.65+/-0.08 for norfluoxetine at +40 mV, respectively. In inside-out patches, norfluoxetine applied to the cytoplasmic surface inhibited Kv3.1 with an IC(50) value of 0.19+/-0.01 microM. The inhibition of Kv3.1 currents by both drugs was characterized by an acceleration in the apparent rate of current decay, without modification of the activation time course and with relatively fewer effects on peak amplitude. The degree of inhibition of Kv3.1 by norfluoxetine was voltage-dependent. The inhibition increased steeply between 0 and +30 mV, which corresponded with the voltage range for channel opening. In the voltage range positive to +30 mV, inhibition displayed a weak voltage dependence, consistent with an electrical distance delta of 0.31+/-0.05. The association (k(+1)) and dissociation (k(-1)) rate constants for norfluoxetine-induced inhibition of Kv3.1 were 21.70+/-3.39 microM(-1) s(-1) and 14.68+/-3.94 s(-1), respectively. The theoretical K(D) value derived by k(-1)/k(+1) yielded 0.68 microM. Norfluoxetine did not affect the ion selectivity of Kv3.1. The reversal potential under control conditions was about -85 mV and was not affected by norfluoxetine. Norfluoxetine slowed the deactivation time course, resulting in a tail crossover phenomenon when the tail currents, recorded in the presence and absence of norfluoxetine, were superimposed. The voltage dependence of steady-state inactivation was not changed by the drug. Norfluoxetine produced use-dependent inhibition of Kv3.1 at a frequency of 1 Hz and slowed the recovery from inactivation. It is concluded that at clinically relevant concentrations, both fluoxetine and its major metabolite norfluoxetine inhibit Kv3.1, and that norfluoxetine directly inhibits Kv3.1 as an open channel blocker.

Algorithms↗

Perceptual grouping via spatial selection in a focused-attention task.

Theories of attention can be separated into those that select by location, and those that select by location-invariant representation. Experiments demonstrating stronger interference or facilitation from distractors grouped by nonspatial features with the target than ungrouped distractors have been considered as evidence for the selection of location-invariant representations. However, few studies have measured spatial attention directly at the locations of the grouped or ungrouped objects. In these experiments subjects responded to spatial probes (dots) while also identifying a cued target letter among distractors. Probe responses were faster for distractor locations with the target color than for those with the nontarget color, implying that target-color locations receive more attention. This pattern of spatial attention may explain why target-color distractors interfere more with target identification than nontarget-color distractors. These results suggest that although attention can be directed by nonspatial properties such as grouping by color or organization of the scene into objects, selection may ultimately be based on location.

Attention↗

Patient compliance and persistence with antihyperglycemic drug regimens: evaluation of a medicaid patient population with type 2 diabetes mellitus.

BACKGROUND: Drug use patterns among patients with type 2 diabetes mellitus have been studied in the general population but not specifically in the Medicaid population. OBJECTIVE: The purpose of this study was to examine antihyperglycemic drug use patterns among Medicaid recipients with type 2 diabetes and assess patients' persistence and compliance with different antihyperglycemic drug regimens. METHODS: Pharmaceutical claims data from Medi-Cal for January 1996 through September 1998 were analyzed to investigate antihyperglycemic drug use patterns over a 1-year and 2-year period. Prescription refill data were examined to assess patient compliance and persistence. RESULTS: Of the 37,431 patients in the 1-year follow-up cohort, 79.6% started antihyperglycemic treatment with monotherapy (ie, drug therapy with a single class of antihyperglycemic medication), 14.5% with insulin alone, 3.9% with polytherapy (ie, drug therapy with > or = 2 classes of medication other than insulin), and 2.1% with insulin plus another therapy. Of the patients receiving monotherapy, 85.3% were taking a sulfonylurea, 14.0% were taking metformin, and 0.7% were taking another agent. In the 1-year follow-up, 55.5% of patients taking metformin alone, 67.2% of those taking sulfonylurea alone, and 83.9% of those taking metformin plus sulfonylurea (M + S) did not undergo any modification of their regimen (except discontinuation of therapy). Among these patients, those taking metformin or sulfonylurea alone had approximately 65% more days of continuous (or persistent) treatment (129 and 128 days, respectively) per patient per year than did patients taking polytherapy (78 days). In addition, sulfonylurea or metformin monotherapy was associated with a 36% higher compliance rate than M + S polytherapy (177 days vs 130 days). CONCLUSION: Simple 1-drug antihyperglycemic regimens were associated with better compliance and persistence (as measured by prescription refill data) than more complex multiple-drug regimens among patients with type 2 diabetes in the Medi-Cal population.

Adult↗

Effects of hand massage on anxiety in cataract surgery using local anesthesia.

PURPOSE: To evaluate the effects of hand massage on patient anxiety during cataract surgery. SETTING: Kangnam St. Mary's Hospital, Seoul, Korea. METHODS: This study comprised 59 patients having cataract surgery from December 11, 1996, to February 12, 1997. The patients were divided into those having a hand massage 5 minutes before surgery (experimental group, n = 29) and those not receiving a hand massage (control group, n = 30). Patients' anxiety levels were measured using the Visual Analog Scale and by assessing the systolic blood pressure, diastolic blood pressure, and pulse rate before and after the hand massage and 5 minutes before the end of surgery. Epinephrine, norepinephrine, cortisol, blood sugar levels, neutrophil, and lymphocyte percentages in white blood cells were also measured. RESULTS: After the hand massage, the psychological anxiety levels, systolic and diastolic blood pressures, and pulse rate were significantly lower than before the massage. The hand massage significantly decreased epinephrine and norepinephrine levels in the experimental group. Epinephrine, norepinephrine, and cortisol levels increased in the control group. The differences between groups were significant. There were no significant between-group differences in blood sugar levels or neutrophil and lymphocyte percentages in white blood cells. CONCLUSION: The findings indicate that hand massage decreases the psychological and physiological anxiety levels in patients having cataract surgery under local anesthesia.

Adult↗