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K Park

Publications and source records attributed to K Park.

At least 73 records · Page 4Linked to original sources
PubMed2001

Novel sigmaF-dependent genes of Escherichia coli found using a specified promoter consensus.

Availability of whole genome information opens new bioinformatics approaches to study global regulation. We developed a program, named ScanProm, that allows to search a genome database for promoter consensus elements. The program uses a multiple alignment of previously identified components of a regulon as an input and generates a consensus profile. The profile is then optimized by adjusting the cutoff value for position-specific similarity assessment and used for a genome scan to search for unknown members of the regulon. The candidates obtained are scored by their similarity to the consensus profile. The ScanProm program was applied to search for novel members of the class III flagellar regulon of Escherichia coli. The search template included the previously defined 4 bp (-35) and 8 bp (-10) promoter elements, presumably recognized by the flagellar-specific sigmaF, with additional 4 bp at the 3' of the -35 consensus. The majority of highly scoring candidates obtained from the whole genome sequence scan were known class III genes, although several new genes were also identified. We tested 10 novel highly scoring candidate class III genes by cloning their promoter fragments into a fusion vector designed to monitor the transcriptional activity with lacZ. Two of these genes, b2737(ygbK) and ppdAB, were found to be dependent on FlhDC, the master regulator of the flagellar genes. The regulation of these genes by sigmaF was further confirmed by comparing their expression in the wild-type and fliA backgrounds. An overproduction or inactivation of these genes did not exhibit any notable phenotypes in motility or chemotaxis.

Base Sequence↗
PubMed2001

Expression of volume-sensitive Cl(-) channels and ClC-3 in acinar cells isolated from the rat lacrimal gland and submandibular salivary gland.

1. The expression of ClC-3 was examined in rat lacrimal gland and submandibular salivary gland cells using RT-PCR and Western analysis. Whole-cell patch clamp methods were used to investigate the expression of volume-sensitive anion channels in acinar cells isolated from these tissues. 2. Expression of mRNA encoding ClC-3, and ClC-3 protein, was found in rat submandibular gland by RT-PCR and Western analysis. Rat lacrimal gland cells, however, did not appear to express mRNA encoding for ClC-3, nor the ClC-3 protein. 3. Volume-sensitive anion conductances were observed in both rat lacrimal gland and submandibular salivary gland acinar cells. The conductance was of a similar size in the two cell types, but was much slower to activate in the lacrimal cells. 4. The properties of the conductances in lacrimal and submandibular cells were similar, e.g. halide selectivity sequence (P(I) > P(Cl) > P(aspartate)) and inhibition by 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid, 5-nitro-2-(3-phenylpropylamino)-benzoate and tamoxifen. 5. The data suggest that the expression of ClC-3 is not an absolute requirement for the activity of volume-sensitive anion channels in rat lacrimal gland acinar cells.

Animals↗
PubMed2001

Protein kinase A activation phosphorylates the rat ClC-2 Cl- channel but does not change activity.

Phosphorylation-dependent events have been shown to modulate the activity of several members of the mammalian CLC Cl- channel gene family, including the inward rectifier ClC-2. In the present study we investigated the regulation of rat ClC-2 expressed in the TSA-201 cell line (a transformed HEK293 cell line that stably expresses the SV40 T-antigen) by protein kinases. Protein kinase A activation phosphorylated ClC-2 in vivo, whereas stimulation of protein kinase C with phorbol 12-myristate 13-acetate did not. In vitro labeling studies confirmed that protein kinase A could directly phosphorylate ClC-2, and that protein kinase C and Ca2+/calmodulin-dependent protein kinase II did not. Nevertheless, protein kinase A-dependent phosphorylation of CLC-2 failed to regulate either the magnitude or the kinetics of the hyperpolarization-activated Cl- currents. Considered together, we demonstrate that protein kinase A activation results in the phosphorylation of rat ClC-2 in vivo, but this event is independent of Cl- channel activity.

Adenosine Triphosphate↗
PubMed2001

DnaA boxes in the P1 plasmid origin: the effect of their position on the directionality of replication and plasmid copy number.

The DnaA protein is essential for initiation of DNA replication in a wide variety of bacterial and plasmid replicons. The replication origin in these replicons invariably contains specific binding sites for the protein, called DnaA boxes. Plasmid P1 contains a set of DnaA boxes at each end of its origin but can function with either one of the sets. Here we report that the location of origin-opening, initiation site of replication forks and directionality of replication do not change whether the boxes are present at both or at one of the ends of the origin. Replication was bidirectional in all cases. These results imply that DnaA functions similarly from the two ends of the origin. However, origins with DnaA boxes proximal to the origin-opening location opened more efficiently and maintained plasmids at higher copy numbers. Origins with the distal set were inactive unless the adjacent P1 DNA sequences beyond the boxes were included. At either end, phasing of the boxes with respect to the remainder of the origin influenced the copy number. Thus, although the boxes can be at either end, their precise context is critical for efficient origin function.

Bacterial Proteins↗
PubMed2001

Cytologic evaluation of cyclin D1 expression in primary breast carcinoma.

BACKGROUND: Preoperative assessment of the biologic characteristics of primary breast carcinoma is important because neoadjuvant medical therapy is being used increasingly. In the current study, the authors attempted to evaluate the validity of cyclin D1 assay in fine-needle aspiration (FNA) samples from patients with primary breast carcinoma. METHODS: FNA samples were obtained prior to therapy and multiple slides were stored at -80 degrees C for subsequent immunocytochemical analysis (ICA). ICA for cyclin D1 protein was performed on FNA samples from 51 breast carcinoma patients and 20 samples from patients with benign breast disease. In 45 breast carcinoma patients who had undergone surgery, sections were taken from paraffin blocks and stained by ICA for cyclin D1 validation. Possible correlations between cyclin D1 expression in the FNA samples and the biologic data of the patients also were analyzed. RESULTS: Cyclin D1 expression was detected in 37 FNA samples from 51 breast carcinomas (72.5%) whereas expression of cyclin D1 was detected in 8 FNA samples from 20 patients with benign breast disease (40%). In histologic sections after surgery, 26 cases of breast carcinoma (65%) showed a positive reaction to cyclin D1. Concordance for the presence of cyclin D1 between FNA samples and histologic samples was 75%. Cyclin D1 expression was high in patients with the tumors that expressed estrogen receptor (ER) (30 of 34 vs. 5 of 11; P = 0.028) and progesterone receptor (PR) (33 of 38 vs. 2 of 7; P = 0.007). There was no significant relation found between cyclin D1 expression and tumor size or lymph node metastasis. Cyclin D1 expression within invasive ductal carcinoma was observed in > 80% of low or intermediate nuclear grade tumors but its expression decreased to 61.5% (8 of 13 cases) in tumors with high nuclear grade (P = 0.023). All 14 breast carcinomas in which the S-phase fraction was </= 15% showed a high degree of cyclin D1 expression whereas 4 of 6 tumors (66.7%) in which the S-phase fraction was > 15% showed cyclin D1 expression. Cyclin D1 expression was found to be correlated inversely with proliferative activity in breast carcinoma (P = 0.023). CONCLUSIONS: The results of the current study show that cyclin D1 expression can be measured by ICA in FNA samples with reasonable concordance with the results of histologic section. Cyclin D1 expression was found to be associated with ER/PR status and cell differentiation. The results of the current study indicate that the measurement of novel molecular markers could be performed adequately in FNA samples as well as in histologic sections.

Adult↗
PubMed2001

Inhibition of epithelial cell apoptosis by Porphyromonas gingivalis.

Porphyromonas gingivalis is periodontal pathogen that is capable of invading gingival epithelial cells (GECs). Apoptotic responses of primary cultures of GECs to P. gingivalis were investigated with a DNA fragmentation ELISA assay. P. gingivalis induced a transient increase in GEC DNA fragmentation; however, after prolonged incubation GECs did not undergo apoptosis. Furthermore, P. gingivalis blocked apoptosis in GECs following stimulation with camptothecin. Immunoblotting of GECs with Bcl-2 or Bax antibodies showed that P. gingivalis up-regulated Bcl-2 levels in GECs, whereas Bax levels were transiently elevated and declined after 24 h stimulation. Streptococcus gordonii did not affect levels of either molecule. RT-PCR demonstrated that induction of Bcl-2 occurs at the transcriptional level. The results suggest that P. gingivalis can inhibit apoptosis in GECs by up-regulation of the anti-apoptotic molecule Bcl-2. The prevention of host cell apoptosis may represent a strategy for P. gingivalis survival within invaded GECs.

Apoptosis↗
PubMed2001

beta-Cell dysfunction rather than insulin resistance is the main contributing factor for the development of postrenal transplantation diabetes mellitus.

BACKGROUND: Our study was undertaken to investigate the pathogenesis and possible risk factors for postrenal transplantation diabetes mellitus (PTDM). METHODS: We recruited 114 patients with normal glucose tolerance (NGT) and performed both 75-g oral glucose tolerance tests (OGTT) and short insulin tolerance tests 1 week before and 9-12 months after transplantation. RESULTS: The subjects were classified into three groups by World Health Organization criteria on the basis of OGTT after transplantation: (a) 36 (31.6%) subjects with normal glucose tolerance; (b) 51 (45.7%) subjects with impaired glucose tolerance (IGT); and (c) 27 (23.7%) subjects with postrenal transplantation diabetes mellitus. Dosages of steroid and cyclosporine were equivalent among the three groups. Before transplantation, the fasting and 2-hr plasma glucose and proinsulin/insulin (PI/I) ratios were significantly higher in the IGT and PTDM groups than in the NGT group, but the insulin sensitivity index (ISI) was not significantly different among the three groups. In addition, the area under the curve-insulin on OGTT was significantly lower in the PTDM group than in the NGT group. After transplantation, however, the ISI was increased in all groups. Furthermore, the ISI and PI/I ratios revealed significantly higher values in the PTDM group than in the NGT group after transplantation. CONCLUSIONS: These results revealed that fasting and 2-hr plasma glucose levels, as well as the proinsulin/insulin ratio before transplantation, are both possible indicators of beta-cell dysfunction and may be predictors for the development of PTDM. Furthermore, beta-cell dysfunction, rather than insulin resistance, was proven to be the main factor for the pathogenesis of PTDM.

Adult↗
PubMed2001

Binary spreading process with parity conservation.

Recently there has been a debate concerning the universal properties of the phase transition in the pair contact process with diffusion (PCPD) 2A-->3A, 2A-->0. Although some of the critical exponents seem to coincide with those of the so-called parity-conserving universality class, it was suggested that the PCPD might represent an independent class of phase transitions. This point of view is motivated by the argument that the PCPD does not conserve parity of the particle number. In the present work we question what happens if the parity conservation law is restored. To this end, we consider the reaction-diffusion process 2A-->4A, 2A-->0. Surprisingly, this process displays the same type of critical behavior, leading to the conclusion that the most important characteristics of the PCPD is the use of binary reactions for spreading, regardless of whether parity is conserved or not.

Journal Article↗
PubMed2001

Defective fluid secretion and NaCl absorption in the parotid glands of Na+/H+ exchanger-deficient mice.

Multiple Na(+)/H(+) exchangers (NHEs) are expressed in salivary gland cells; however, their functions in the secretion of saliva by acinar cells and the subsequent modification of the ionic composition of this fluid by the ducts are unclear. Mice with targeted disruptions of the Nhe1, Nhe2, and Nhe3 genes were used to study the in vivo functions of these exchangers in parotid glands. Immunohistochemistry indicated that NHE1 was localized to the basolateral and NHE2 to apical membranes of both acinar and duct cells, whereas NHE3 was restricted to the apical region of duct cells. Na(+)/H(+) exchange was reduced more than 95% in acinar cells and greater than 80% in duct cells of NHE1-deficient mice (Nhe1(-/-)). Salivation in response to pilocarpine stimulation was reduced significantly in both Nhe1(-/-) and Nhe2(-/-) mice, particularly during prolonged stimulation, whereas the loss of NHE3 had no effect on secretion. Expression of Na(+)/K(+)/2Cl(-) cotransporter mRNA increased dramatically in Nhe1(-/-) parotid glands but not in those of Nhe2(-/-) or Nhe3(-/-) mice, suggesting that compensation occurs for the loss of NHE1. The sodium content, chloride activity and osmolality of saliva in Nhe2(-/-) or Nhe3(-/-) mice were comparable with those of wild-type mice. In contrast, Nhe1(-/-) mice displayed impaired NaCl absorption. These results suggest that in parotid duct cells apical NHE2 and NHE3 do not play a major role in Na(+) absorption. These results also demonstrate that basolateral NHE1 and apical NHE2 modulate saliva secretion in vivo, especially during sustained stimulation when secretion depends less on Na(+)/K(+)/2Cl(-) cotransporter activity.

Animals↗
PubMed2001

Rituximab using a thrice weekly dosing schedule in B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma demonstrates clinical activity and acceptable toxicity.

PURPOSE: Rituximab has been reported to have little activity in small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL) and to be associated with significant infusion-related toxicity. This study sought to decrease the initial toxicity and optimize the pharmacokinetics with an alternative treatment schedule. PATIENTS AND METHODS: Thirty three patients with SLL/CLL received dose 1 of rituximab (100 mg) over 4 hours. In cohort I (n = 3; 250 mg/m(2)) and cohort II (n = 7; 375 mg/m(2)) rituximab was administered on day 3 and thereafter three times weekly for 4 weeks using a standard administration schedule. Cohort III (n = 23; 375 mg/m(2)) administered rituximab similar to cohort II for the first two treatments and then over 1 hour thereafter. RESULTS: A total of 33 CLL/SLL patients were enrolled; only one patient discontinued therapy because of infusion-related toxicity. Thirteen patients developed transient hypoxemia, hypotension, or dyspnea that were associated with significant changes in baseline interleukin-6, interleukin-8, tumor necrosis factor alpha, and interferon gamma compared with those not experiencing such reactions. Infusion-related toxicity occurred more commonly in older (median age 73 v 62 years; P =.02) patients with no other pretreatment clinical or laboratory features predicting occurrence of these events. The overall response rate was 45% (3% CR, 42% PR; 95% CI 28% to 64%). Median response duration for these 15 patients was 10 months (95% CI, 6.8-13.2; range, 3 to 17+). CONCLUSION: Rituximab administered thrice weekly for 4 weeks demonstrates clinical efficacy and acceptable toxicity. Initial infusion-related events seem to be cytokine mediated and resolve by the third infusion making rapid administration possible. Future combination studies of rituximab with other therapies in CLL seem warranted.

Aged↗
PubMed2001

Ratio of donor kidney weight to recipient bodyweight as an index of graft function.

Reduced renal mass or mismatching kidney size are risk factors for chronic allograft nephropathy. We assessed the effect of mismatching donor kidney weight and recipient bodyweight on renal graft function in 82 live donor kidney transplant recipients who did not have acute rejection. We calculated the donor kidney weight to recipient bodyweight ratio, and established the relation between this ratio and renal indices with a mixed model regression. We showed that recipients with a high ratio had better graft function.

Adult↗
PubMed2001

Interleukin 12 gene therapy of cancer by peritumoral injection of transduced autologous fibroblasts: outcome of a phase I study.

A phase I dose-escalation clinical trial of peritumoral injections of interleukin 12 (IL-12)-transduced autologous fibroblasts was performed in patients with disseminated cancer for whom effective treatment does not exist. The goals of this study were to assess the safety and toxicities as well as the efficacy, and ancillarily the immunomodulatory effects, of peritumoral IL-12 gene transfer. Primary dermal fibroblasts cultured from the patients were transduced with retroviral vector carrying human IL-12 genes (p35 and p40) as well as the neomycin phosphotransferase gene (TFG-hIL-12-Neo). Patients received four injections at intervals of 7 days. Nine patients were enrolled in this dose-escalation study, with secreted IL-12 doses ranging from 300 ng/24 hr for the first three patients to 1000, 3000, and 5000 ng/24 hr for two patients in each subsequent dosage level. Although a definite statement cannot be made, there appears to be perturbation of systemic immunity. Also, the locoregional effects mediated by tumor necrosis factor alpha (TNF-alpha) and CD8+ T cells were observed with tumor regression. Treatment-related adverse events were limited to mild to moderate pain at the injection site; clinically significant toxicities were not encountered. Transient but clear reductions of tumor sizes were observed at the injected sites in four of nine cases, and at noninjected distant sites in one melanoma patient. Hemorrhagic necrosis of tumors was observed in two melanoma patients. These data indicate that gene therapy by peritumoral injection of IL-12-producing autologous fibroblasts is feasible, and promising in patients with advanced cancer.

Adult↗
PubMed2001

Congestion of right liver graft in living donor liver transplantation.

BACKGROUND: Left liver graft from a small donor will not meet the metabolic demands of a larger adult recipient. One solution to this problem is to use a right liver graft without a middle hepatic vein (MHV). However, the need for drainage from the MHV tributaries has not yet been described. METHODS: Five right liver grafts without a MHV were transplanted in patients including two hepatitis B virus-cirrhosis, two fulminant hepatic failure and one secondary biliary cirrhosis. The graft weight ranged from 650 to 1,000 g, corresponding to 48 to 83% of the standard liver volume of the recipients. RESULTS: Two of five recipients were complicated with severe congestion of the right median sector immediately after reperfusion, followed by prolonged massive ascites and severe liver dysfunction. One of the patients died of sepsis with progressive hepatic dysfunction 20 days after the operation. CONCLUSIONS: Preservation and reconstruction of the MHV tributaries is recommended to prevent congestion of the right liver graft without MHV.

Body Weight↗
PubMed2001

Nonequilibrium roughening transition in a volume conserving system.

We introduce a simple volume conserving stochastic model undergoing a nonequilibrium roughening transition (NRT) in 1+1 dimensions. In our model, there is no deposition and evaporation of a particle breaking the volume conserving condition. The degree of roughness of the fluctuating interface in our model is determined by whether or not the hopping of a particle depends on the local slope of the interface. The hopping process of a particle is controlled by the probability 0 1/2, a particle tends to hop in the uphill direction, and so the interface cannot reach a saturated phase. When p=1/2, the hopping of a particle does not depend on the local slope of the interface. Then the interface can reach a saturated phase. The saturated interface at p=1/2 is in a rough phase with a nonzero roughness exponent. Our model, therefore, exhibits the NRT at the critical parameter p(c)=1/2.

Journal Article↗
PubMed2001

Synthesis of 3-indolyl-2,5-dihydroxybenzoquinones.

[figure: see text] 3-Indolylquinones can be efficiently prepared by the acid-catalyzed condensation of Indoles with 2,5-dichiorobenzoquinone, followed by DDQ oxidation. The resulting dichloroquinones are hydrolyzed to the 3-indolyidihydroxybenzoquinones. The 3-indolylquinone substructure is of interest because of its presence in natural products that modulate biological processes through protein-protein interactions, including the asterriquinones.

Benzoquinones↗
PubMed2001

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↗
PubMed2001

Identification of a heparin binding domain in the N-terminal cleavage site of pro-islet amyloid polypeptide. Implications for islet amyloid formation.

Islet amyloid deposits are a characteristic pathologic lesion of the pancreas in type 2 diabetes and are composed primarily of the islet beta cell peptide islet amyloid polypeptide (IAPP or amylin) as well as the basement membrane heparan sulfate proteoglycan perlecan. Impaired processing of the IAPP precursor has been implicated in the mechanism of islet amyloid formation. The N- and C-terminal cleavage sites where pro-IAPP is processed by prohormone convertases contain a series of basic amino acid residues that we hypothesized may interact with heparan sulfate proteoglycans. This possibility was tested using affinity chromatography by applying synthetic fragments of pro-IAPP to heparin-agarose and heparan sulfate-Sepharose. An N-terminal human pro-IAPP fragment (residues 1-30) was retained by both heparin-agarose and heparan sulfate-Sepharose, eluting at 0.18 m NaCl at pH 7.5. Substitution of alanine residues for two basic residues in the N-terminal cleavage site abolished heparin and heparan sulfate binding activity. At pH 5.5, the affinity of the wild-type peptide for heparin/heparan sulfate was increased, implying a role for histidine residues at positions 6 and 28 of pro-IAPP. A C-terminal pro-IAPP fragment (residues 41-67) had no specific affinity for either heparin or heparan sulfate, and the N- or C-terminal fragments had only weak affinity for chondroitin sulfate. These data suggest that monomeric N-terminal human pro-IAPP contains a heparin binding domain that is lost during normal processing of pro-IAPP.

Amino Acid Sequence↗