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Biomedical subjects

S Kim

Publications and source records attributed to S Kim.

At least 865 records · Page 48Linked to original sources
PubMed1996

Sustained-release morphine for epidural analgesia in rats.

BACKGROUND: Epidural opioid analgesia often requires either continuous infusion or repeated injections, which are inconvenient for patients, increase risk of infection, and consume expensive physician and nursing time. In addition, potential respiratory depression is a major safety concern. The authors studied whether a single dose of epidurally administered, sustained-release morphine could prolong analgesia and reduce toxic effects in rats. METHODS: Sustained-release morphine (DTC401) was prepared by encapsulating morphine sulfate in DepoFoam (Dep. Tech, San Diego, CA), a lipid-based, sustained-release drug delivery system. A standard hot-plate test for analgesia, pulse oximetry for hemoglobin oxygen saturation, corneal-reflex loss, and incidence of catalepsy were used to assess efficacy and toxicities. Cerebrospinal fluid and serum pharmacokinetic studies were performed after a single epidural dose, using a commercially available radioimmunoassay kit. RESULTS: Single epidural doses of DTC401 resulted in equivalent onset time to peak analgesia but significantly prolonged analgesia compared with morphine sulfate. Hemoglobin oxygen saturation was decreased minimally, and the incidences of catalepsy and corneal-reflex loss were minimal, even at large doses of DTC401. In contrast, the larger doses of morphine sulfate significantly decreased hemoglobin oxygen saturation, and caused catalepsy and loss of the corneal-reflex. The Cmax for DTC401 was 32% in cerebrospinal fluid and 6% in serum, relative to morphine sulfate. The terminal half-life for DTC401 was increased 32 fold in the cerebrospinal fluid compared with morphine sulfate. CONCLUSIONS: A single epidural dose of DTC401, compared with morphine sulfate, prolonged duration of analgesia, with minimal supraspinal toxic effects, in rats.

Analgesia, Epidural↗
PubMed1996

Essential role of NF-kappa B in transactivation of the human immunodeficiency virus long terminal repeat by the human cytomegalovirus 1E1 protein.

The 72 kDa 1E1 protein of human cytomegalovirus (HCMV) is one of a few viral regulatory proteins expressed immediately after infection of a host cell. Although it is now well-established that 1E1 is a potent transcriptional activator of the human immunodeficiency virus (HIV) long terminal repeat (LTR), the identity of the nucleotide sequence responsive to 1E1 remains elusive and the molecular mechanism of this interaction is not well-understood. We have constructed various LTR mutants and tested them for their ability to be activated by 1E1 using transient transfection assays. Mutations in the NF-kappa B sites, of either a few changes in the nucleotide sequence or a deletion of the entire region, abrogated 1E1-driven transactivation. Deletion of the Tat-responsive element (TAR) had no significant effect on reporter expression. Mutations in the Sp1 sites or the TATA box significantly lowered LTR activity, but this is probably due to an effect on the general transcription system, as these elements are also required for the transactivation of the LTR by many stimulators including Tat, tumour necrosis factor alpha (TNF-alpha). E1A/E1B and phorbol myristate acetate (PMA). In addition, gel retardation analysis demonstrated that NF- kappa B activity was significantly increased in human T lymphoid H9 and monocytic U937 cell lines constitutively expressing 1E1. Taken together, these data suggest that NF- kappa B plays a central role in the 1E1 transactivation of the HIV LTR.

Base Sequence↗
PubMed1996

Impact of childhood cancer on religious life of Korean families.

This paper reports on the social and personal relevance of religious faith entering into the situation of family stress due to the illness of a child with cancer. The expectations of religious faith may include, objectively, the actual physical healing of the child or the determination of the child's fate; it may include, subjectively, the hope for emotional support, the provision of moral guidance in time of difficulty, or an overarching life-view. There were major religious changes in 20% of the families. While all the major religious faiths in South Korea were represented in the study, 61% of the sample identified Christianity as their primary religious response.

Adaptation, Psychological↗
PubMed1996

Characterization of an Escherichia coli mutant, feeA, displaying resistance to the calmodulin inhibitor 48/80 and reduced expression of the rare tRNA3Leu.

We previously described a mutation feeB1 conferring a temperature-sensitive filamentation phenotype and resistance to the calmodulin inhibitor 48/80 in Escherichia coli, which constitutes a single base change in the acceptor stem of the rare tRNA3Leu recognizing CUA codons. We now describe a second mutant, feeA1, unlinked to feeB, but displaying a similar phenotype, 48/80 resistance and a reduced growth rate at the permissive temperature, 30 degrees C, and temperature-sensitive, forming short filaments at 42 degrees C. In the feeA mutant, tRNA3Leu expression (but not that of tRNA1Leu) was reduced approximately fivefold relative to the wild type. We previously showed that the synthesis of beta-galactosidase, which unusually requires the translation of 6-CUA codons, was substantially reduced, particularly at 42 degrees C, in feeB mutants. The feeA mutant also shows drastically reduced synthesis of beta-galactosidase at the non-permissive temperature and reduced levels even at the permissive temperature. We also show that increased copy numbers of the abundant tRNA1Leu, which can also read CUA codons at low efficiency, suppressed the effects of feeA1 under some conditions, providing further evidence that the mutant was deficient in CUA translation. This, and the previous study, demonstrates that mutations which either reduce the activity of tRNA3Leu or the cellular amount of tRNA3Leu confer resistance to the drug 48/80, with concomitant inhibition of cell division at 42 degrees C.

Codon↗
PubMed1996

Effects of an AT1 receptor antagonist, an ACE inhibitor and a calcium channel antagonist on cardiac gene expressions in hypertensive rats.

1. This study was undertaken to determine whether the AT1 receptor directly contributes to hypertension-induced cardiac hypertrophy and gene expressions. 2. Stroke-prone spontaneously hypertensive rats (SHRSP) were given orally an AT1, receptor antagonist (losartan, 30 mg kg-1 day-1), an angiotensin converting enzyme inhibitor (enalapril 10 mg kg-1 day-1), a dihydropyridine calcium channel antagonist (amlodipine, 5 mg kg-1 day-1), or vehicle (control), for 8 weeks (from 16 to 24 weeks of age). The effects of each drug were compared on ventricular weight and mRNA levels for myocardial phenotype- and fibrosis-related genes. 3. Left ventricular hypertrophy of SHRSP was accompanied by the increase in mRNA levels for two foetal phenotypes of contractile proteins (skeletal alpha-actin and beta-myosin heavy chain (beta-MHC)), atrial natriuretic polypeptide (ANP), transforming growth factor-beta-1 (TGF-beta 1) and collagen, and a decrease in mRNA levels for an adult phenotype of contractile protein (alpha-MHC). Thus, the left ventricle of SHRSP was characterized by myocardial transition from an adult to a foetal phenotype and interstitial fibrosis at the molecular level. 4. Although losartan, enalapril and amlodipine lowered blood pressure of SHRSP to a comparable degree throughout the treatment, losartan caused regression of left ventricular hypertrophy of SHRSP to a greater extent than amlodipine (P < 0.01). 5. Losartan significantly decreased mRNA levels for skeletal alpha-actin, ANP, TGF-beta 1 and collagen types I, III and IV and increased alpha-MHC mRNA in the left ventricle of SHRSP. Amlodipine did not alter left ventricular ANP, alpha-MHC and collagen types I and IV mRNA levels of SHRSP. 6. The effects of enalapril on left ventricular hypertrophy and gene expressions of SHRSP were similar to those of losartan, except for the lack of inhibition of collagen type I expression by enalapril. 7. Unlike the hypertrophied left ventricle, there was no significant difference between losartan and amlodipine in the effects on non-hypertrophied right ventricular gene expressions of SHRSP. 8. Our results show that hypertension causes not only left ventricular hypertrophy but also molecular transition of myocardium to a foetal phenotype and interstitial fibrosis-related molecular changes. These hypertension-induced left ventricular molecular changes may be at least in part mediated by the direct action of local angiotensin II via the AT1, receptor.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Pharmacokinetic study of zonisamide in patients undergoing brain surgery.

To test whether the concentration of the anticonvulsant zonisamide in erythrocytes reflects the brain concentration and the clinical response of the drug, its pharmacokinetics were studied in nine patients undergoing surgery for brain tumour. Erythrocyte, total and free serum concentrations in samples drawn on the day of brain surgery were compared with levels on a day after the operation. In three patients zonisamide and its major metabolite, 2-sulphamoylacetylphenol, were also analysed in urine. The area under the curve of the free and the erythrocyte concentration did not differ between the two study phases whereas the area under the curve of the total serum concentration was significantly lower on the day of the operation, and this was associated with significant increases in total clearance (15.4 compared with 12.7 mL kg-1 h-1, P < 0.05, n = 9) and renal clearance (5.4 compared with 3.3 mL kg-1 h-1, P < 0.05, n = 3), and non-significant change in non-renal clearance (7.7 on the day of operation compared with 8.4 mL kg-1 h-1 on the post-operation day, n = 3). Zonisamide distribution was also altered by the operative procedure, as evidenced by a higher volume of distribution (1.48 compared with 0.87 L kg-1, P < 0.05, n = 9). The binding of zonisamide was characterized on both days. Zonisamide binding to erythrocytes seemed to occur by two processes: a saturable process and a non-saturable linear process. The maximum binding capacity to erythrocytes (31.6 vs 29.7 micrograms mL-1) did not differ on the two days; however, increases in the dissociation binding constant (+28%) and the proportionality constant (+24%) were observed on the day of the operation, suggesting that the zonisamide concentration in erythrocytes was greater on the day of the operation. Brain surgery appears to be one of the possible factors altering the rate of elimination of zonisamide and the uptake of the drug by erythrocytes.

Adult↗
PubMed1996

The IE2 regulatory protein of human cytomegalovirus induces expression of the human transforming growth factor beta1 gene through an Egr-1 binding site.

Increases in transforming growth factor beta1 (TGF-beta1) mRNA and biological activity in the early phase of human cytomegalovirus (CMV) infection in fibroblasts are paralleled by increased TGF-beta1-chloramphenicol acetyltransferase (CAT) reporter gene activity. To determine how CMV infection transactivates the TGF-beta1 promoter, we examined the effects of the cotransfected IE2 regulatory protein of human CMV on 5'-deleted TGF-beta1 promoter-CAT reporter genes in transient DNA transfection assays. Two upstream TGF-beta1 promoter regions each containing an Egr-1 consensus site were shown to be important for IE2-induced transactivation in a cell type that displayed greatly reduced nonspecific activity. Furthermore, transfer of an Egr-l site from between positions -125 and -98, but not point mutant versions of this site, to a heterologous promoter also conveyed IE2 responsiveness. Addition of an IE2 expression vector or use of the U373 A45 astrocytoma cell line expressing IE2 also produced synergistic stimulation of GAL4-Egr-l-mediated activation of a target promoter containing GAL4 binding sites. The 80-kDa IE2 protein present in A45 cells proved to selectively bind to glutathione S-transferase (GST)-Egr-1 beads. The results of in vitro protein binding assays also revealed that an intact in vitro-translated IE2 protein bound directly to the GST-Egr-1 fusion protein through the zinc finger domain of the Egr-1 protein and that this binding activity was abolished by deletion of parts of the zinc finger DNA-binding domain. Similarly, the Egr-1 protein was found to associate preferentially with a small region within the C-terminal half of the IE2 protein adjacent to the DNA-binding and dimerization domains that are important for both transactivation and downregulation. We conclude from these observations that IE2 may regulate transcription of the TGF-beta1 gene as well as other potential cellular targets by virtue of its ability to interact with the Egr-1 DNA-binding protein.

Astrocytoma↗
PubMed1996

Experimental Bacillus cereus post-traumatic endophthalmitis and treatment with ciprofloxacin.

BACKGROUND: Bacillus species remain an important cause of post-traumatic endophthalmitis, often causing permanent visual loss. METHODS: Twenty two rabbits were used to evaluate the clinical and histological findings of Bacillus cereus experimental post-traumatic endophthalmitis. Eyes that had received a scleral laceration and surgical repair were inoculated with Bacillus cereus. Thirty four other rabbits were used to evaluate the efficacy of intravitreal ciprofloxacin in treating experimental disease. RESULTS: Animals developed a post-traumatic endophthalmitis that closely mimicked human disease, characterised by a rapidly progressive and destructive endophthalmitis. Histological evaluation revealed retinal detachment, retinal necrosis, and the infiltration of inflammatory cells into the subretinal space. Intravitreal ciprofloxacin (100 micrograms) prevented the development of disease when given 1 hour and 6 hours after trauma and inoculation. CONCLUSIONS: Clinical and histological examination of experimental Bacillus cereus post-traumatic endophthalmitis suggests that retinal detachment and retinal necrosis play important roles in visual loss. Ciprofloxacin may be of benefit in the management of certain intraocular infections following penetrating injury.

Animals↗
PubMed1996

Role of angiotensin-converting enzyme, adrenergic receptors, and blood pressure in cardiac gene expression of spontaneously hypertensive rats during development.

We undertook this study to investigate the regulatory mechanism of cardiac gene expression in spontaneously hypertensive rats (SHR) during development. We measured cardiac mRNAs by Northern blot analysis. In 9-week-old SHR at the very early stage of cardiac hypertrophy, the expression of various cardiac genes related to the regulation of cardiac contraction and relaxation was already significantly changed compared with control Wistar-Kyoto rats, indicating that cardiac molecular changes are responsible for cardiac remodeling or the modulation of cardiac performance in SHR. We gave various types of antihypertensive drugs, at oral doses causing a mild and comparable hypotensive effect, to 27-week-old SHR to examine the effects on the altered cardiac gene expression. Imidapril, an angiotensin-converting enzyme inhibitor, normalized the increased gene expression of atrial natriuretic polypeptide and collagen types I and III and the decreased expression of alpha-myosin heavy chain in SHR heart. Atenolol (a beta 1-blocker) combined with doxazosin did not affect cardiac ANP and alpha-myosin heavy chain expression of SHR but normalized the increased collagen expression. In contrast, despite a hypotensive effect comparable to these two drug treatments, doxazosin (an alpha 1-blocker) alone or manidipine (a calcium antagonist) did not normalize these altered gene expressions of SHR. These results show that the cardiac renin-angiotensin system is involved in the altered cardiac gene expression in SHR. The beta 1- but not alpha 1-adrenergic receptor is also responsible for the increased cardiac collagen expression in SHR.

Actins↗
PubMed1996

Selective blockade of endothelin receptor subtypes on systemic and renal vascular responses to endothelin-1 and IRL1620, a selective endothelin ETB-receptor agonist, in anesthetized rats.

By using BQ-788 as a selective endothelin ETB-receptor antagonist and FR139317 as a selective endothelin ETA-receptor antagonist, we have characterized the receptor subtypes mediating the systemic and renal vascular effects of endothelin-1 and IRL1620, a selective endothelin ETB-receptor agonist (succinyl-[Glu9,Ala11,5]-endothelin-1(8-21)), in anesthetized rats. Bolus intravenous injection of endothelin-1 (0.5 nmol/kg) and IRL1620 (1.65 nmol/kg) produced a transient fall in systemic blood pressure followed by a sustained increase. The initial fall in blood pressure observed after endothelin-1 and IRL1620 administration was completely blocked by BQ-788 (0.5 mumol/kg, i.v.), whereas the pressor response was blocked by FR139317 (0.8 mumol/kg, i.v.). Renal blood flow was decreased and calculated renal vascular resistance was dramatically increased by endothelin-1 and IRL1620. The reduction of renal blood flow by endothelin-1 was significantly suppressed by FR139317 but potentiated by BQ-788. Both BQ-788 and FR139317 partially blocked the renal vasoconstriction by IRL1620. Pretreatment by BQ-788 itself decreased renal blood flow by 14.1%. These results indicate that the systemic depressor responses induced by endothelin-1 and IRL1620 are mediated through the endothelin ETB-receptor, and the pressor responses are mediated through the endothelin ETA-receptor. In the renal vasculature of anesthetized rats, it is suggested that vasoconstriction is mediated through both endothelin ETA- and ETB-receptors and that endothelin ETB-receptors may be also involved in vasodilating responses to endothelin peptides.

Anesthesia↗
PubMed1996

Role of platelet-activating factor and prostanoids in hemodynamic changes in rat experimental endotoxic shock.

The present experiments were conducted to elucidate the role of platelet-activating factor (PAF) and cyclooxygenase products in the cardiovascular responses to endotoxin in anesthetized rats. Endotoxin (10 mg/kg, i.v.) induced hypotension that was accompanied by a decrease in cardiac output and an increase in calculated total peripheral resistance, suggesting that this hypotension mainly resulted from the reduced cardiac output. The endotoxin-induced decrease in cardiac output and hemoconcentration was significantly attenuated by TCV-309 (a PAF receptor antagonist), ibuprofen (a cyclooxygenase inhibitor) or S-1452 (a thromboxane A2/prostaglandin H2-receptor antagonist). During the 3-hr observation period following endotoxin administration, ibuprofen and S-1452 showed only early protection and TCV-309 showed late attenuation of the endotoxin-induced hypotension. Tachycardiac responses to endotoxin were only blocked by ibuprofen but not by TCV-309 or S-1452. These results suggest that both PAF and cyclooxygenase product(s), including thromboxane A2, mediate the decrease in cardiac output and hypotension in rat experimental endotoxic shock. Cyclooxygenase product(s) other than thromboxane A2 or prostaglandin endoperoxide may be involved in the endotoxin-induced increase in heart rate.

Animals↗
PubMed1996

Postcardiac injury syndrome. An immunologic pleural fluid analysis.

The postcardiac injury syndrome (PCIS) is characterized by inflammation of the pericardium, pleura, and pulmonary parenchyma following a variety of cardiac injuries. Although it has been clinically recognized for decades, confirmation of the syndrome has been problematic owing to lack of a sufficiently diagnostic test. Previously, we have reported pleural fluid characteristics which help to exclude other diagnoses that may mimic the syndrome. We describe the first immunologic assessment, including antimyocardial antibody testing, of pleural fluid from a patient with PCIS which supports a local immunologic mechanism in the pathogenesis of the syndrome. These results support the important role of pleural fluid analysis in the diagnosis of PCIS.

Adult↗
PubMed1996

Characteristics of gsp-positive growth hormone-secreting pituitary tumors in Korean acromegalic patients.

A subset of human growth hormone (GH)-secreting pituitary tumors contains the gsp oncogene that encodes an activation mutation of the alpha-subunit of the stimulatory GTP-binding protein (G(S) alpha). This study was undertaken to investigate the frequency of the gsp oncogene in GH-secreting pituitary tumors in Korean acromegalic patients and to elucidate the clinical characteristics of these patients to endocrine testing. Direct polymerase chain reaction sequencing revealed the gsp oncogene mutation in 9 out of 21 tumors (43%) at amino acid 201 of the G(S) alpha protein. A single nucleotide mutation in the tumors carrying the gsp oncogene was observed, which replaced an arginine (CGT) in the normal protein with cysteine (TGT) in eight tumors and serine (AGT) in one tumor. The patients with the gsp oncogene mutation (group 1) were older (54 +/- 10 vs 41 +/- 11 years, p = 0.0085) than those without the mutation (group 2). Sex, tumor size and grade, basal GH and prolactin levels, the GH response to oral glucose loading, the GH fluctuation and the paradoxical response to thyrotropin-releasing hormone or gonadotropin-releasing hormone did not differ between the groups. The gsp oncogene was found mostly in somatotroph adenomas. The octreotide-induced GH suppression was significantly higher in group 1 than in group 2 (95 +/- 5% vs 81 +/- 17%, p = 0.0335). The GH response to bromocriptine did not differ between the groups. These results suggest that the G(S) alpha mutations of GH-secreting tumor are observed in Korean acromegalic patients with similar frequency to those of western countries. The patients with gsp oncogene are likely to be older than those without the oncogene, and show excellent response of GH suppression to octreotide.

Acromegaly↗