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Biomedical subjects

K M Kim

Publications and source records attributed to K M Kim.

At least 55 records · Page 3Linked to original sources
PubMed2001

Cloning and characterization of a hydroxycinnamoyl-CoA:tyramine N-(hydroxycinnamoyl)transferase induced in response to UV-C and wounding from Capsicum annuum.

Hydroxycinnamoyl-CoA : tyramine N-(hydroxycinnamoyl) transferase (THT) is a pivotal enzyme in the synthesis of N-(hydroxycinnamoyl)-amines, which are associated with cell wall fortification in plants. The cDNA encoding THT was cloned from the leaves of UV-C treated Capsicum annuum (hot pepper) using a differential screening strategy. The predicted protein encoded by the THT cDNA is 250 amino acids in length and has a relative molecular mass of 28,221. The protein sequence derived from the cDNA shares 76% and 67% identity with the potato and tobacco THT protein sequences, respectively. The recombinant pepper THT enzyme was purified using a bacterial overexpression system. The purified enzyme has a broad substrate specificity including acyl donors such as cinnamoyl-, sinapoyl-, feruloyl-, caffeoyl-, and 4-coumaroyl-CoA and acceptors such as tyramine and octopamine. In UV-C treated plants, the THT mRNA was strongly induced in leaves, and the elevated level of expression was stable for up to 36 h. THT mRNA also increased in leaves that were detached from the plant but not treated with UV-C. THT expression was measured in different plant tissues, and was constitutive at a similar level in leaf, root, stem, flower and fruit. Induction of THT mRNA was correlated with an increase in THT protein.

Acyltransferases↗
PubMed2001

Age dependence of laryngeal chemoreflex in puppies.

Previously collected data have indicated that the laryngeal chemoreflex (LCR) response is exaggerated during a critical period of postnatal development in several experimental animals. These animals had fewer anatomic and physiological similarities to humans than do puppies. This investigation of the LCR in 14 anesthetized puppies was undertaken to determine age-related differences in the response to stimulation of the supraglottic laryngeal mucosa by saline solution, distilled water, cow's milk, and acid at pH 1.0. The dogs were divided into 3 age groups: group 1 consisted of 4 dogs that were 2 weeks old, and in groups 2 and 3 there were 5 puppies each, of 4 and 6 weeks of age, respectively. The LCR response (laryngospasm, apnea, respiratory depression, and bradycardia) was found in the puppies only after stimulation of the laryngeal mucosa with acid at pH 1.0, and it was more easily achieved in the 4- and 6-week age groups than in the 2-week group. These findings suggest that the LCR is an age-dependent response that appears in dogs only after 2 weeks of age. The important implication of this finding is that postnatal neural maturation may influence the laryngeal reflex in humans to some extent.

Age Factors↗
PubMed2001

Anti-stress and anti-fatigue effects of fermented rice bran.

The anti-stress and anti-fatigue effects on rats and mice of a hot water extract of rice bran fermented with Saccharomyces cerevisae IFO 2346 were investigated. Oral administration (1 g/kg/day) of the hot water extract of fermented rice bran (FRB) inhibited major changes in the weight of the adrenal, thymus, spleen and thyroid, showing an anti-stress effect. The hot water extract of FRB also inhibited increases in the GPT and LDH activity, cholesterol and glucose in the serum. The administration (1 g/kg/day) for 2 weeks significantly prolonged the swimming time, resulting in an increase in the anti-fatigue effect. It is considered from these results that FRB had anti-stress and anti-fatigue effects.

Adjuvants, Immunologic↗
PubMed2001

Cephalic spreading levels after volumetric caudal epidural injections in chronic low back pain.

The volumetric caudal epidural steroid injection has been advocated to facilitate the delivery of medications to the lesion site. This study was aimed to examine the actual spreading patterns of this technique, using epidurogram. A total of 32 patients with chronic low back pain accompanied by radiculopathy of various causes (degenerative spondylosis, herniated nucleus pulposus, spondylolisthesis, and spinal stenosis) were included. The volumetric caudal epidural injection of the 10 mL mixture of contrast medium 5 mL, 0.5% bupivacaine 1 mL, triamcinolone 1.5 mL (60 mg) and normal saline 25 mL was performed. Immediately after the cessation of the first spread, the subsequent solution of another 10 mL of contrast medium 5 mL, 0.5% bupivacaine 1 mL and normal saline 4 mL was injected. This procedure was repeated serially until the total volume to be 50 mL. Continuous fluoroscopic imaging was obtained after each injection. Average time taken to complete the study was 37 sec per every 10 mL. The spreading levels of the mixture were distributed mainly at mid to lower lumbar area in the majority of the patients. During the subsequent injections, the levels were not changed significantly. This was thought to be due to the minimal resistance in cephalad direction, anatomic variations and Starling effect of epidural space.

Adult↗
PubMed2000

Fas-mediated apoptosis and expression of related genes in human malignant hematopoietic cells.

Fas transduces apoptotic signals upon cross-linking with the Fas ligand (FasL), which is experimentally replaced by agonistic anti-Fas monoclonal antibodies (mAb). Of eight human malignant hematopoietic cell lines (HL-60, KG-1, THP-1, K562, U937, Jurkat, IM-9, RPMI-8226) examined by flow cytometric analysis, all, except K562, were found to be positive for surface Fas antigen. However, despite surface Fas expression, the agonistic anti-Fas mAb (7C11) induced apoptosis in only three of seven Fas-expressing cell lines (KG-1, Jurkat and IM-9). This Fas-resistance did not correlated with high levels of mRNA either for DcR3, a decoy receptor for FasL, or for FAP-1, a Fas-associated phosphatase that can block the apoptotic function of Fas. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis did not show consistent differences in the expression of Bcl-2 and Bax between Fas-sensitive and Fas-resistant cell lines examined. These findings indicated that the presence or absence of mRNA expression of DcR3, FAP-1, Bcl-2 and Bax did not always correlate with relative sensitivity to Fas-mediated apoptosis. Treatment of cells with cycloheximide converted the phenotype of resistant cell lines from Fas-resistant to Fas-sensitive, and enhanced the sensitivity of Fas-sensitive cell lines. These results suggest that the Fas-resistance is dependent on the presence of labile proteins that determine resistance to Fas-mediated apoptosis and the apoptotic machinery is already in place in Fas-resistant cell lines.

Apoptosis↗
PubMed2000

Sphingosine 1-phosphate protects human umbilical vein endothelial cells from serum-deprived apoptosis by nitric oxide production.

Sphingosine 1-phosphate (S1P) can prevent endothelial cell apoptosis. We investigated the molecular mechanisms and signaling pathways by which S1P protects endothelial cells from serum deprivation-induced apoptosis. We show here that human umbilical vein endothelial cells (HUVECs) undergo apoptosis associated with increased DEVDase activity, caspase-3 activation, cytochrome c release, and DNA fragmentation after 24 h of serum deprivation. These apoptotic markers were suppressed by the addition of S1P, the NO donor S-nitroso-N-acetylpenicillamine (100 micrometer), or caspase-3 inhibitor z-VAD-fmk. The protective effects of S1P were reversed by the nitric-oxide synthase (NOS) inhibitor N-monomethyl-l-arginine, but not by the soluble guanylyl cyclase inhibitor 1H-(1,2,4)oxadiazolo[4,3-a]-quanoxaline-1-one, suggesting that NO, but not cGMP, is responsible for S1P protection from apoptosis. Furthermore, S1P increased NO production by enhancing Ca(2+)-sensitive NOS activity without changes in the eNOS protein level. S1P-mediated cell survival and NO production were suppressed significantly by pretreatment with antisense oligonucleotide of EDG-1 and partially by EDG-3 antisense. S1P-mediated NO production was suppressed by the addition of pertussis toxin, an inhibitor of G(i) proteins, the specific inhibitor of phospholipase C (PLC), and the Ca(2+) chelator BAPTA-AM. These findings indicate that S1P protects HUVECs from apoptosis through the activation of eNOS activity mainly through an EDG-1 and -3/G(i)/PLC/Ca(2+) signaling pathway.

Apoptosis↗
PubMed2000

Intraoperative thermal regulation in patients undergoing laparoscopic vs open surgical procedures.

BACKGROUND: Although perioperative hypothermia is a well-known consequence of general anesthesia, it has been hypothesized that laparoscopic surgery exacerbates hypothermia to a greater extent than open surgery. The aim of this study was to demonstrate that laparoscopic surgery does not represent an increased risk for hypothermia. METHODS: A case-controlled retrospective study was conducted on 45 patients, 25 undergoing laparoscopic cholecystectomy and 20 undergoing parathyroid surgery under endotracheal general anesthesia. Data were collected regarding age, sex, weight, height, American Society of Anesthesiologists (ASA) status, length of surgery, and anesthesia. In addition, we analyzed the type of intraoperative intravenous fluids, anesthetics and perioperative drugs, and temperature, blood pressure, and heart rate recordings during anesthesia. RESULTS: There was no significant difference between the two groups with respect to age, sex, body mass index (BMI), ASA status, type or amount of intravenous fluids infused, length of anesthesia or surgery, changes in mean blood pressure, or heart rate. Core body temperatures in both groups decreased significantly over time (p 0.05). There was no difference between the groups in terms of maximum drop in temperature (lowest temperature recorded vs baseline temperature) (1.1 +/- 0.7 vs 1.0 +/- 0.7 degrees C, p > 0.05). CONCLUSION: This study demonstrates that patients who undergo laparoscopic and open procedures of similar duration under endotracheal general anesthesia have similar profiles in terms of perioperative hypothermia.

Anesthesia, General↗
PubMed2000

Analysis of OPT8511 RAPD fragments closely linked with cold sensitivity at seedling stage in rice (Oryza sativa L.).

OPT8(511) was confirmed to be strongly associated with cold sensitivity of rice by random amplified polymorphic DNA (RAPD) analysis for the cold tolerance with 94 F2 population crossed with 'Dular' (cold sensitive cultivar) and 'Toyohatamochi' (cold resistant cultivar). A DNA marker from the RAPD fragment, OPT8(511), has been cloned with genomic DNA from rice cultivar ('Dular') and the nucleotide sequence has been determined. The nucleotide sequence revealed that the putative open reading frame was 511 base pairs and contained 169 amino acid residues. It is 79% and 57% identical to the rice cDNA (C26347) in DataBank at the nucleotide and amino acid sequence levels, respectively. The clone OPT8(511) specifically amplified a 511 bp band from the DNA of cold sensitive cultivars. Use of this marker could facilitate early selection of character associated with cold tolerance in rice.

Amino Acid Sequence↗
PubMed2000

Prognostic implications of microsatellite genotypes in gastric carcinoma.

Microsatellite alterations such as loss of heterozygosity (LOH) and microsatellite instability (MSI) are observed in most (70% to 80%) gastric carcinomas. To determine whether the microsatellite genotypes are correlated with clinicopathological features, 118 patients with gastric carcinomas were examined by using polymorphic microsatellite markers for LOH on 5 gastric cancer-associated chromosome arms and non-polymorphic BAT markers for MSI. Microsatellite genotypes were categorized as high-frequency MSI (MSI-H), high-level LOH (LOH-H), low-level LOH (LOH-L) and LOH non-detectable (LOH-N). A significant fraction of the MSI-H, LOH-H and LOH-L types was observed in intestinal-type gastric carcinomas, whereas the LOH-N type was highly associated with diffuse-type tumors (p = 0.00162). There was a close relationship between microsatellite genotype and TNM (tumor-node-metastasis) stage (p = 0. 001). Univariate analysis showed that patients of LOH-H or LOH-N types and those of MSI-H or LOH-L types correlated with poor and favorable survival, respectively, not only in all tumor stages (p = 0.0001) but also in stages II and III (p = 0.0271). It is likely that the major genotypes of gastric carcinomas can be placed into at least 4 microsatellite categories, thus allowing the construction of a comprehensive genetic classification useful for the prediction of diverse clinical courses.

Adult↗
PubMed2000

A phase Ib/II trial of granulocyte-macrophage-colony stimulating factor and interleukin-2 for renal cell carcinoma patients with pulmonary metastases: a case of fatal central nervous system thrombosis.

BACKGROUND: Interleukin-2 (IL-2) and granulocyte-macrophage-colony stimulating factor (GM-CSF) are cytokines with nonoverlapping pleiotropic effects. In a prior Phase Ib study, this combination of agents exhibited antitumor effects in the lungs of four of eight patients with renal cell carcinoma and pulmonary metastases. We conducted this Phase Ib/II trial to determine the response rate of renal cell carcinoma patients with pulmonary metastases treated with continuous infusion IL-2 plus GM-CSF. METHODS: Patients with renal cell carcinoma and pulmonary metastases were treated with 1.5, 2.25, or 4.5 x 10(6) IU/m(2)/day 96-hour continuous infusion IL-2 on Days 1-4, 8-11, and 15-18, and 1.25, 2.25, or 2.5 microg/kg/day GM-CSF on Days 8-19. RESULTS: Sixteen patients were treated per protocol, 14 of whom could be evaluated for disease progression. None of these 14 patients had >50% shrinkage of either total tumor burden or pulmonary metastasis. One patient developed Grade 5 neurotoxicity. Autopsy revealed acute multifocal cerebral venous thrombosis as well as acute subdural and subarachnoid hemorrhage. CONCLUSIONS: The combination of IL-2 and GM-CSF may be associated with marked morbidity and, as in one case in this study, mortality. No significant antitumor activity was appreciated. Thus, the combination of IL-2 and GM-CSF, when administered at this dose and according to this schedule, does not appear to be active in renal cell carcinoma and is associated with significant toxicities. Further studies using this combination of agents should only be undertaken with extreme caution and particular attention to neurotoxicity.

Adult↗
PubMed2000

Synthesis and oral antitumor activity of tetrakis(carboxylato)platinum(IV) complexes.

A novel class of tetrakis(carboxylato)platinum(IV) complexes, [Pt(O(2)CR)(4)(dach)] (dach = trans-(+/-)-1,2-diaminocyclohexane; R = C(n)H(2n+1), n = 1 approximately 5), was synthesized and studied for physicochemical properties and oral antitumor activity. Lipophilicity and aqueous solubility of the title complexes were greatly dependent on the alkyl chain length of the carboxylate ligand, and their partition coefficient and solubility changed by 4 or 5 orders of magnitude from acetate to hexanoate complexes. On the other hand, the range of their cathodic reduction potential (-546 approximately -403 mV) depending on the chain length of the carboxylate ligand was relatively small. Among the title complexes, the tetrakis(propionato)platinum(IV) complex, [Pt(O(2)CC(2)H(5))(4)(dach)], with appropriate lipophilicity (log P = 0.18) and aqueous solubility (14.6 mg/mL) was found to exhibit better oral antitumor activity than JM216 against the human ovarian tumor xenograft SKOV3 in nude mice.

Administration, Oral↗
PubMed2000

A broad-spectrum caspase inhibitor blocks concanavalin A-induced hepatitis in mice.

Fulminant hepatic failure (FHF) is a clinical syndrome resulting from massive death of liver cells or sudden and severe impairment of liver function. The causes of FHF are diverse and the overall mortality is very high. Recently, it became clear that apoptosis of hepatocytes is the critical cause of acute hepatic failure in FHF. It is well known that a family of cysteine proteases called caspase is one of the key mediators of the apoptotic pathway. Thus, caspases are attractive potential targets for the treatment of disorders resulting from excessive apoptosis. In this report, we examined the activity of a new caspase inhibitor, Xyz 033 mp. This nonpeptide inhibitor showed broad-spectrum caspase-inhibiting activity and protected primary rat hepatocytes from apoptotic death. In a mouse model of FHF induced by concavalin A (Con A), Xyz 033 mp suppressed elevated AST and ALT and specifically reduced IL-1 beta concentration. Also, Xyz 033 mp rescued mice from lethal experimental hepatitis induced by Con A. In addition, histological examinations indicated that Xyz 033 mp protected hepatocytes from the fatal apoptogenic effect of Con A. These results suggest that Xyz 033 mp may be a candidate therapeutic agent for FHF caused by massive apoptotic death of hepatocytes.

Animals↗
PubMed2000

Dosimetry of rhenium-188 diethylene triamine penta-acetic acid for endovascular intra-balloon brachytherapy after coronary angioplasty.

To examine the possibility of using rhenium-188 diethylene triamine penta-acetic acid (DTPA) for endovascular intra-balloon brachytherapy after angioplasty, dose distribution around the balloon was calculated and validated by film dosimetry. Medical internal radiation dosimetry (MIRD) was calculated assuming that the balloon had ruptured and that the contents had been released into the systemic circulation. 188Re-perrhenate eluate from the 188W/188Re generator was concentrated using an ion column and used to label DTPA. The dose distribution around the angioplasty balloon (20 mm length, 3 mm diameter cylinder) was estimated by Monte Carlo simulation using the EGS4 code. The time required for 17.6 Gy to be absorbed at 1 mm from the balloon's surface following application of 3700 MBq/ml of 188Re was found to be 278 s. Fifty percent of the energy was deposited in the first millimetre of the vessel wall from the balloon's surface. The calculated radiation absorbed dose agreed with that measured by film dosimetry, which was performed using a water phantom, with errors ranging from 9.4% to 17%. Upon balloon rupture the total amount of 188Re-DTPA was presumed to enter the systemic circulation. The resulting radiation absorbed dose was calculated using the MIRDOSE3 program and residence times obtained from dogs and amounted to 0.0056 mGy/MBq to the whole body and 4.56 mGy/MBq to the urinary bladder. The absorbed dose of 188Re-DTPA to the whole body was one-tenth of that of 188Re-perrhenate. A window-based program was developed to calculate the exposure time and the radiation dose absorbed as a function of the 188Re concentration and the arbitrary distance from the balloon to the surrounding tissues. We conclude that 188Re-DTPA is easy to prepare, safe to use and suitable for intra-balloon brachytherapy after coronary angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed2000

Expression of tenascin-C in astrocytic tumors: its relevance to proliferation and angiogenesis.

BACKGROUND: The expression and distribution of the extracellular matrix protein tenascin-C (TN-C) may be enhanced in human astrocytomas. The purpose of this study is to evaluate the expression of TN-C according to histological malignancy of tumor cells and its relevance to neoplastic angiogenesis in human astrocytic tumors. METHODS: Between 1994 and 1998, 52 astrocytic tumor specimens including 4 pilocytic astrocytomas, 13 astrocytomas, 3 anaplastic astrocytomas, and 32 glioblastomas were used in this study. A retrospective analysis was performed to evaluate a statistical correlation between TN-C expression and proliferative indices. We characterized the expression of TN-C in neoplastic vessels, around individual tumor cells as a tumor network, and in tumor cells by immunohistochemistry using antibodies against human TN-C. The proliferative indices were also investigated by immunostaining with the MIB-1 antibody against the Ki-67 proliferation antigen. RESULTS: TN-C immunoreactivity was found to be enhanced in tumor vessels and tumor networks of high-grade astrocytic tumors. The vascular TN-C deposition was greater in high-grade than in low-grade astrocytic tumors (p < 0.05). Its expression was the most intense in glioblastomas. Proliferation indices increased with tumor grade and MIB-1 labeling index (LI) was highest in glioblastomas. Moreover, expression of TN-C in tumor vessels was correlated with proliferative indices. CONCLUSIONS: Our data show that TN-C in human astrocytic tumors may be identified as a factor contributing to malignant progression. And also, enhanced expression of TN-C in tumor vessels having a high proliferative index indicates that TN-C could be involved in neoplastic angiogenesis.

Adolescent↗
PubMed2000

Computations for group sequential boundaries using the Lan-DeMets spending function method.

We describe an interactive Fortran program which performs computations related to the design and analysis of group sequential clinical trials using Lan-DeMets spending functions. Many clinical trials include interim analyses of accumulating data and rely on group sequential methods to avoid consequent inflation of the type I error rate. The computations are appropriate for interim test statistics whose distribution or limiting distribution is multivariate normal with independent increments. Recent theoretical results indicate that virtually any design likely to be used in a clinical trial will fall into this category. Interim analyses need not be equally spaced, and their number need not be specified in advance. In addition to determining sequential boundaries using an alpha spending function, the program can perform power computations, compute probabilities associated with a given set of boundaries, and generate confidence intervals.

Clinical Trials as Topic↗
PubMed2000

Low-dose cytarabine maintenance therapy vs observation after remission induction in advanced acute myeloid leukemia: an Eastern Cooperative Oncology Group Trial (E5483).

The Eastern Cooperative Oncology Group (ECOG) conducted a prospective phase III study in patients with relapsed/refractory acute myeloid leukemia (AML) to evaluate whether administration of repeated courses of low-dose cytarabine (LDAC) maintenance therapy after induction of complete remission in advanced AML would improve disease-free and overall survival. Patients with AML in second/later relapse or refractory disease were first treated with a combination of high-dose cytarabine and amsacrine. Those who achieved complete remission were then randomized to observation or to receive LDAC, 10 mg/m2 subcutaneously twice a day x2 21 days every 2 months until relapse occurred. Of 86 patients eligible for randomization, 41 patients were assigned to receive LDAC and 45 patients to observation. The median disease-free survival was 7.4 months for patients assigned to LDAC compared to 3.3 months for patients receiving no additional therapy, P= 0.084. The median survival from randomization was 10.9 months and 7.0 months for patients receiving LDAC maintenance chemotherapy and observation, respectively (P= 0.615). The data from this study suggest that LDAC maintenance therapy given to patients with advanced AML who achieve complete remission can increase disease-free survival compared to observation, but does not improve overall survival. Nevertheless, because of the ineffectiveness and toxicity of intensive post-remission chemotherapy in this circumstance, LDAC maintenance therapy, a tolerable outpatient regimen, offers the potential for improved quality of life.

Acute Disease↗
PubMed2000

Efficient induction of an antigen-specific, T helper type 1 immune response by interleukin-12-secreting fibroblasts.

To determine whether the paracrine secretion of interleukin (IL)-12 can efficiently convert immune responses characterized by high levels of synthesis of IL-4 and immunoglobulin E (IgE) into T helper 1 (Th1)-dominated responses, 3T3 fibroblasts were stably transfected to secrete IL-12 (480 units/10(6) cells/48 hr). Their effects on the T helper cell-mediated immune response were investigated in ovalbumin (OVA)-primed mice. Free mouse recombinant IL-12 was included as a control group. IL-12-secreting fibroblasts (3T3/IL-12) were more effective than free recombinant IL-12 at increasing OVA-specific interferon-gamma (IFN-gamma) production and decreasing OVA-specific IL-4 production in CD4+ T cells. In addition, injection with 3T3/IL-12 cells significantly increased anti-OVA immunoglobulin G2a (IgG2a) levels and decreased anti-OVA IgE levels in OVA-primed mice. This work suggests that IL-12-secreting fibroblasts can efficiently induce an antigen-specific Th1 response and may be beneficial in the treatment of diseases caused by undesirable T helper 2 (Th2)-dominated responses, including allergic diseases.

Animals↗