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Biomedical subjects

K Park

Publications and source records attributed to K Park.

At least 19 recordsLinked to original sources
PubMed2003

Even-odd effect in spontaneously coherent bilayer quantum Hall droplets.

Using exact diagonalization in the disk geometry we predict a novel even-odd effect in the Coulomb-blockade spectra of vertically coupled double quantum dots under an external magnetic field. The even-odd effect in the tunneling conductance is a direct manifestation of spontaneous interlayer phase coherence, and is similar to the even-odd resonance in the Cooper pair box problem in mesoscopic superconducting grains. Coherent fluctuations in the number of Cooper pairs in superconductors are analogous to the fluctuations in the relative number difference between the two layers in quantum Hall droplets.

Journal Article↗
PubMed2003

Topoisomerase II-alpha (topoII) and HER2 amplification in breast cancers and response to preoperative doxorubicin chemotherapy.

A significant proportion of breast cancers with HER2 amplification have simultaneous amplification of topoisomerase II-alpha (topoII). Amplification of HER2 and topoII was assayed using a novel chromogenic in situ hybridisation (CISH) method. HER2 and topoII amplification status and the response to preoperative doxorubicin chemotherapy were analysed in 67 locally advanced breast cancer patients. Response to chemotherapy was increased in the cases with coamplification of HER2 and topoII (18/19), whereas the response rate was significantly decreased in the cases without HER2 and topoII amplification (17/36). The 12 cases with HER2 amplification alone showed an intermediate response rate (9/12). The findings of the current study indicate that topoII amplification may play a role in determining chemosensitivity of breast cancers to doxorubicin chemotherapy.

Adult↗
PubMed2003

Postoperative chemoradiotherapy for gastric cancer.

BACKGROUND: We report the results of postoperative chemoradiotherapy after curative resection in gastric cancer patients. PATIENTS AND METHODS: Patients with gastric cancer staged IB to IV(M0) were treated with chemoradiotherapy after curative resection with extensive (D2) lymph node dissection. Nodal metastases were observed in 261 (90%) patients. The chemotherapy consisted of fluorouracil 400 mg/m(2) plus leucovorin 20 mg/m(2) for 5 days, followed by 4500 cGy of radiotherapy for 5 weeks with fluorouracil and leucovorin on the first 4 days and the last 3 days of radiotherapy. Two 5-day cycles of chemotherapy were given 4 weeks after the completion of radiotherapy. RESULTS: Of 290 patients accrued, 229 (79%) patients completed chemoradiotherapy as planned. With a median follow-up of 49 months, 114 (34%) patients have relapsed: 33 (29%) locoregional relapses, 76 (67%) peritoneal relapses and 41 (36%) distant metastases. The 5-year overall and relapse-free survivals were 60% and 57%, respectively. Tolerance was acceptable, the main toxicity being neutropenia. CONCLUSIONS: This postoperative chemoradiotherapy after curative resection of gastric cancer was feasible, with acceptable toxicities. Whether this adjuvant therapy in gastric cancer patients that have undergone a D2 lymph node dissection impacts on survival or reduces the incidence of relapses remains to be studied.

Adenocarcinoma↗
PubMed2002

Platelet recovery after eradication of Helicobacter pylori in patients with idiopathic thrombocytopenic purpura.

The association between Helicobacter pylori ( H. pylori) infection and idiopathic thrombocytopenic purpura (ITP) has been reported by several groups. We investigated the prevalence of H. pylori infection and the effectiveness of its eradication in Japanese patients with ITP. H. pylori infection was found in 21 of 30 patients (70.0%) by (13)C urea breath test and presence of serum antibodies to H. pylori. H. pylori was eradicated in 18 of the 21 infected patients (85.7%) by administration of a proton pump inhibitor and two kinds of antibiotics. In only one patient was medication discontinued due to skin rash on the 4th day of treatment. Platelet recovery was obtained in ten patients (55.6%). In two patients with treatment failure, platelet recovery was obtained after successful re-eradication. In three patients without H. pylori infection, platelet counts did not significantly increase with the same treatment. On the other hand, eradication therapy did not affect platelet counts in patients with gastric ulcer. In conclusion, H. pylori eradication can be used for initial treatment with tolerable adverse effects in some ITP patients.

Adult↗
PubMed2002

Swelling-induced Ca2+ release from intracellular calcium stores in rat submandibular gland acinar cells.

The effects of osmotically-induced cell swelling on cytoplasmic free Ca2+ concentration ([Ca2+]i) were studied in acinar cells from rat submandibular gland using microspectrofluorimetry. Video-imaging techniques were also used to measure cell volume. Hypotonic stress (78% control tonicity) caused rapid cell swelling reaching a maximum relative volume of 1.78 +/- 0.05 (n = 5) compared to control. This swelling was followed by regulatory volume decrease, since relative cell volume decreased significantly to 1.61 +/- 0.08 (n = 5) after 10 min exposure to hypotonic medium. Osmotically induced cell swelling evoked by medium of either 78% or 66% tonicity caused a biphasic increase of [Ca2+]i. The rapid phase of this increase in [Ca2+]i was due to release of Ca2 + from intracellular stores, since it was also observed in cells bathed in Ca2+-free solution. The peak increase of [Ca2+]i induced by cell swelling was 3.40 +/- 0.49 (Fura-2 F340/F380 fluorescence ratio, n = 11) and 3.17 +/- 0.43 (n = 17) in the presence and the absence of extracellular Ca2+, respectively, corresponding to an absolute [Ca2+]i of around 1 microm. We found that around two-thirds of cells tested still showed some swelling-induced Ca2+ release (SICR) even after maximal concentrations (10(-5) M - 10(-4) M) of carbachol had been applied to empty agonist-sensitive intracellular Ca2+ stores. This result was confirmed and extended using thapsigargin to deplete intracellular Ca2+ pools. Hypotonic shock still raised [Ca2+]i in cells pretreated with thapsigargin, confirming that at least some SICR occurred from agonist-insensitive stores. Furthermore, SICR was largely inhibited by pretreatment of cells with carbonyl cyanide m-cholorophenyl hydrazone (CCCP) or ruthenium red, inhibitors of mitochondrial Ca2+ uptake. Our results suggest that the increase in [Ca2+]i, which underlies regulatory volume decrease in submandibular acinar cells, results from release of Ca2+ from both agonist-sensitive and mitochondrial Ca2+ stores.

Animals↗
PubMed2002

Expression of a sodium bicarbonate cotransporter in human parotid salivary glands.

The human parotid gland secretes much of the bicarbonate that enters the mouth. Prompted by studies of animal models, this study sought evidence for the expression of a functional Na(+)-HCO(3)(-) cotransporter (NBC) in human parotid acinar cells. Microfluorometric measurements of intracellular pH in isolated acini showed that the recovery from an acid load was achieved in part by HCO(3)(-) uptake via a Na(+)-dependent, DIDS-sensitive mechanism. By reverse transcriptase-polymerase chain reaction, a full-length NBC1 clone was obtained showing more than 99% homology with the human pancreatic isoform hpNBC1. Expressed in Xenopus oocytes, the electrogenicity of the transporter was detected as an inwardly directed, Na(+)- and HCO(3)(-)-dependent flux of negative charge. Immunohistochemistry using antibodies raised to NBC1 showed strong staining of the basolateral membrane of the acinar cells. Therefore, it was concluded that a functional electrogenic Na(+)-HCO(3)(-) cotransporter is expressed in the human parotid gland, and that it contributes to pH regulation in the acinar cells and could play a significant part in salivary secretion.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2002

Clinical features of peripheral T-cell lymphomas in 78 patients diagnosed according to the Revised European-American lymphoma (REAL) classification.

The aim of this study was to analyse the clinical characteristics and prognostic factors of peripheral T-cell lymphomas (PTCLs) according to the Revised European-American Lymphoma (REAL) classification. From 1994 to 1999, 78 patients were diagnosed with PTCLs, excluding cutaneous T-cell lymphomas and T-cell chronic lymphocytic leukaemia. The distribution of the histological subgroups were: PTCL unspecified (PTCL-U), 40%; angiocentric lymphoma, 32%; anaplastic large cell lymphoma (ALCL), 17%; angioimmunoblastic T-cell lymphoma (AILD), 6%; intestinal T-cell lymphoma, 3%; and panniculitic T-cell lymphoma, 3%. Patients with angiocentric lymphoma presented with favourable prognostic factors, whereas those with AILD presented with unfavourable prognostic factors. Most patients were treated with doxorubicin-containing combination chemotherapy (with or without radiation therapy). The overall complete remission rate was 61.2% (95% Confidence Interval (CI): 48.5-72.8%) and the 5-year probability of failure-free survival was 33.5%. Median survival of all patients was 45 months (range 0-64+ months) and the 5-year probability of survival was 36.2%. In the multivariate analysis, only the International Prognosis Index (IPI) was an independent prognostic factor for overall survival (P<0.01). Taken together, the proportion of angiocentric lymphoma in this study was higher than that in the studies of Western countries. PTCL responds poorly to treatment with low survival rates and the IPI is a useful prognostic factor for PTCL.

Adolescent↗
PubMed2002

Solution structure of a cathelicidin-derived antimicrobial peptide, CRAMP as determined by NMR spectroscopy.

CRAMP was identified from a cDNA clone derived from mouse femoral marrow cells as a member of cathelicidin-derived antimicrobial peptides. This peptide shows potent antimicrobial activity against gram-positive and gram-negative bacteria but no hemolytic activity against human erythrocytes. CRAMP was known to cause rapid permeabilization of the inner membrane of Escherichia coli. In this study, the structure of CRAMP in TFE/H2O (1 : 1, v/v) solution was determined by CD and NMR spectroscopy. CD spectra showed that CRAMP adopts a mainly alpha-helical conformation in TFE/H2O solution, DPC micelles, SDS micelles and liposomes, whereas it has a random structure in aqueous solution. The tertiary structure of CRAMP in TFE/H2O (1 : 1, v/v), as determined by NMR spectroscopy, consists of two amphipathic alpha-helices from Leu4 to Lys10 and from Gly16 to Leu33. These two helices are connected by a flexible region from Gly11 to Gly16. Previous analysis of series of fragments composed of various portion of CRAMP revealed that an 18-residue fragment with the sequence from Gly16 to Leu33 was found to retain antibacterial activity. Therefore, the amphipathic alpha-helical region from Gly16 to Leu33 of CRAMP plays important roles in spanning the lipid bilayers as well as its antibiotic activity. Based on this structure, novel antibiotic peptides having strong antibiotic activity, with no hemolytic effect will be developed.

Amino Acid Sequence↗
PubMed2002

A randomized trial of heparin plus ursodiol vs. heparin alone to prevent hepatic veno-occlusive disease after hematopoietic stem cell transplantation.

Hepatic veno-occlusive disease (VOD) is a common and serious regimen-related toxicity after hematopoietic stem cell transplantation (HSCT). There is no safe and proven therapy for established VOD, and focus has been on its prevention. Previous studies have shown that a continuous infusion of unfractionated heparin or ursodiol may reduce the incidence of VOD. In order to compare the efficacy of heparin plus ursodiol with that of heparin alone, we conducted a prospective, randomized study involving 165 consecutive patients who underwent HSCT for a variety of disorders. Eighty-two patients were assigned to receive heparin plus ursodiol, and 83 were assigned to receive heparin alone. Thirteen and 16 patients were diagnosed as having VOD in the heparin plus ursodiol group and the heparin alone group, respectively (15.9% vs 19.3%; P = 0.348). Eighty-nine percent of the heparin plus ursodiol group and 89.2% of the heparin alone group were surviving at day 100 post-HSCT (P = 0.298). The only independent variable associated with an increased risk of VOD was an allogeneic type of HSCT (P = 0.018). In conclusion, this study shows that there is no difference in efficacy between heparin plus ursodiol and heparin alone for the prevention of hepatic VOD.

Adult↗
PubMed2002

Bicycle saddle shape affects penile blood flow.

The purpose of this study was to evaluate the effect of bicycle saddle shape on penile blood flow during cycling. Penile blood flow was measured using a laser Doppler flowmeter in 20 potent male volunteers. In a counterbalanced, crossover design, measurements were taken in the standing and sitting positions, on either a narrow unpadded or wide unpadded saddle, before and after cycling for 5 min. Before cycling, penile blood flow (ml/min/100 g tissue) was significantly decreased from 1.6+/-0.7 to 1.5+/-0.7 (P=0.010) on the wide saddle and from 1.7+/-0.6 to 1.0+/-0.5 (P<0.001) on the narrow saddle. After 5 min of cycling, the changes in penile blood flow on the wide and narrow saddles were 0.34+/-0.49 and -0.38+/-0.49, respectively (P<0.001). The narrow saddle is associated with more significant reductions in penile blood flow and could be a source of blunt perineal trauma, potentially leading to erectile dysfunction.

Adult↗
PubMed2002

Soluble adhesion molecule profile in normal pregnancy and pre-eclampsia.

OBJECTIVE: An exaggerated inflammatory response has been implicated as the cause of endothelial cell dysfunction and the maternal syndrome of pre-eclampsia. Adhesion molecules play a central role in the adherence of leukocytes to endothelial cells and the subsequent migration of white blood cells into perivascular tissue. Cellular forms of adhesion molecules mediate specific steps of leukocyte-endothelial cell interaction, and have been implicated in the pathophysiology of preeclampsia. Soluble forms of these molecules can be detected in plasma, and their concentrations are thought to reflect the degree of activation of a particular cell type. Elevations in soluble P-selectin (sP-selectin) reflect platelet activation; changes in soluble L-selectin (sL-selectin) suggest leukocyte activation; and an increase in soluble forms of E-selectin (sE-selectin), vascular cell adhesion molecule 1 (sVCAM-1), intercellular adhesion molecule 1 (sICAM-1) and platelet endothelial cell adhesion molecule (sPECAM-1) indicate endothelial cell activation/dysfunction. The objective of this study was to determine whether normal pregnancy and pre-eclampsia were associated with changes in the concentrations of soluble selectins and members of the immunoglobulin superfamily of adhesion molecules. STUDY DESIGN: A cross-sectional study was conducted to determine the plasma concentrations of sL-selectin, sE-selectin, sP-selectin, sVCAM-1, sICAM-1 and sPECAM-1 in peripheral blood obtained from non-pregnant women (n = 20), normal pregnant women (n = 100) and patients with pre-eclampsia (n = 55). Concentrations of soluble adhesion molecules were determined with enzyme-linked immunoassays. Parametric statistics were used for data analysis. RESULTS: Normal pregnancy was associated with a significant increase in the maternal plasma concentration of sP-selectin, a decrease in sL-selectin, and no change in sE-selectin, sVCAM-1, sICAM-1 and sPECAM-1. In contrast, pre-eclampsia was associated with a significant increase in sP-selectin, sE-selectin and sVCAM-1, a decrease in sL-selectin, but no change in sICAM-1 and sPECAM-1 concentrations. CONCLUSIONS: The increased concentration of sP-selectin and decreased sL-selectin, as well as the lack of change in endothelial cell-associated soluble adhesion molecules suggest that pregnancy is associated with platelet and leukocyte activation, but not endothelial cell activation. In contrast, pre-eclampsia appears to be characterized by activation of platelets, leukocytes and endothelial cells.

Adolescent↗
PubMed2001

Environment-sensitive hydrogels for drug delivery.

Environmentally sensitive hydrogels have enormous potential in various applications. Some environmental variables, such as low pH and elevated temperatures, are found in the body. For this reason, either pH-sensitive and/or temperature-sensitive hydrogels can be used for site-specific controlled drug delivery. Hydrogels that are responsive to specific molecules, such as glucose or antigens, can be used as biosensors as well as drug delivery systems. Light-sensitive, pressure-responsive and electro-sensitive hydrogels also have the potential to be used in drug delivery and bioseparation. While the concepts of these environment-sensitive hydrogels are sound, the practical applications require significant improvements in the hydrogel properties. The most significant weakness of all these external stimuli-sensitive hydrogels is that their response time is too slow. Thus, fast-acting hydrogels are necessary, and the easiest way of achieving that goal is to make thinner and smaller hydrogels. This usually makes the hydrogel systems too fragile and they do not have mechanical strength necessary in many applications. Environmentally sensitive hydrogels for drug delivery applications also require biocompatibility. Synthesis of new polymers and crosslinkers with more biocompatibility and better biodegradability would be essential for successful applications. Development of environmentally sensitive hydrogels with such properties is a formidable challenge. If the achievements of the past can be extrapolated into the future, however, it is highly likely that responsive hydrogels with a wide array of desirable properties can be made.

Animals↗
PubMed2001

Origin pairing ('handcuffing') as a mode of negative control of P1 plasmid copy number.

In one family of bacterial plasmids, multiple initiator binding sites, called iterons, are used for initiation of plasmid replication as well as for the control of plasmid copy number. Iterons can also pair in vitro via the bound initiators. This pairing, called handcuffing, has been suggested to cause steric hindrance to initiation and thereby control the copy number. To test this hypothesis, we have compared copy numbers of isogenic miniP1 plasmid monomer and dimer. The dimer copy number was only one-quarter that of the monomer, suggesting that the higher local concentration of origins in the dimer facilitated their pairing. Physical evidence consistent with iteron-mediated pairing of origins preferentially in the dimer was obtained in vivo. Thus, origin handcuffing can be a mechanism to control P1 plasmid replication.

DNA Replication↗
PubMed2001

A novel class of highly potent, selective, and non-peptidic inhibitor of Ras farnesyltransferase (FTase).

Design, synthesis and structure-activity relationship of a class of aryl pyrroles as farnesyltransferase inhibitors are described. In vitro and in vivo evaluation of a panel of these inhibitors led to identification of 2 (LB42908) as a highly potent (IC(50)=0.9 nM against H-Ras and 2.4 nM against K-Ras) antitumor agent that is currently undergoing preclinical studies.

Alkyl and Aryl Transferases↗