Biomedical subjects

S R Park

Publications and source records attributed to S R Park.

At least 19 recordsLinked to original sources

PubMed2006

Phase II study of docetaxel and irinotecan combination chemotherapy in metastatic gastric carcinoma.

The current treatment for metastatic gastric cancer (MGC) consists of cisplatin and/or fluorouracil (5-FU) based combination chemotherapy, but cisplatin-based regimens are associated with considerable toxicity. We evaluated the efficacy and safety of a noncisplatin-, non-5-FU-containing regimen, docetaxel/irinotecan in MGC. Chemo-naive patients with MGC received docetaxel (30 mg m(-2)) and irinotecan (70 mg m(-2)) on days 1 and 8 every 3 weeks. The 48 eligible patients (median age 56 years) received a median of four cycles of docetaxel/irinotecan (range 1-18). Of the 46 patients in whom efficacy could be evaluated, 21 showed a partial response (response rate=45.7%; 95% confidence interval (CI) 31.3-60.1%). At a median follow-up of 15.0 months, the median time to progression was 4.5 months (95% CI 3.8-5.2 months) and overall survival was 8.2 months (95% CI, 5.8-10.6 months). Grade 3/4 neutropenia developed in 57.4% of patients, and febrile neutropenia/neutropenic infection in 19.1%. Nonhaematological toxicities were moderate; grade 3/4 diarrhoea occurred in 19.1% of patients, however, was manageable by a dose reduction. There was one possible treatment-related death. In conclusion, weekly docetaxel/irinotecan is a promising outpatient regimen in MGC, with appropriate dose modification.

Adenocarcinoma↗

PubMed2004

Cloning and characterization of ce/8A gene from Rhizobium leguminosarum bv. trifolii 1536.

AIMS: To isolate the cellulase gene from Rhizobium leguminosarum bv. trifolii 1536. METHODS AND RESULTS: By the shot-gun method a clone (cel8A) harbouring 3.1 kb genomic DNA fragment from R. leguminosarum bv. trifolii 1536 was obtained. The cel8A gene coded 348 amino acids and it belongs to the glycosyl hydrolase family 8. The molecular mass of Cel8A protein induced from Escherichia coli DH5alpha, appeared to be 35 kDa. The optimum pH and optimum temperature was 7.0, and about 30 degrees C for its enzymatic activity respectively. CONCLUSIONS: R. leguminosarum bv. trifolii 1536 had cel8A gene having an open reading frame of 1047 bp coded for the activity of hydrolyzation of carboxymethyl cellulose. SIGNIFICANCE AND IMPACT OF THE STUDY: The production of celluloytic enzyme by R. leguminosarum bv. trifolii was confirmed, which would play specific roles in rhizobia. Future study should focus on its role in the infection and nodulation phenomena.

Cellulase↗

PubMed2003

Fate of the peak effect in a type-II superconductor: multicriticality in the Bragg-Glass transition.

We have used small-angle neutron scattering (SANS) and ac magnetic susceptibility to investigate the global magnetic field H vs temperature T phase diagram of a Nb single crystal in which a first-order transition of Bragg-glass melting (disordering), a peak effect, and surface superconductivity are all observable. It was found that the disappearance of the peak effect is directly related to a multicritical behavior in the Bragg-glass transition. Four characteristic phase boundary lines have been identified on the H-T plane: a first-order line at high fields, a mean-field-like continuous transition line at low fields, and two continuous transition lines associated with the onset of surface and bulk superconductivity. All four lines are found to meet at a multicritical point.

Journal Article↗

PubMed2003

The origin of cells that repopulate patellar tendons used for reconstructing anterior cruciate ligaments in man.

Cryopreserved patellar tendon allografts are often recommended for reconstruction of anterior cruciate ligaments (ACLs) because living donor fibroblasts are thought to promote repair. Animal studies, however, indicate that ligaments regenerate from recipient rather than donor cells. If applicable to man, these observations suggest that allograft cell viability is unimportant. We therefore used short tandem repeat analysis with polymerase chain reaction (PCR) amplification to determine the source of cells in nine human ACLs reconstructed with cryopreserved patellar tendon allografts. PCR amplification of donor and recipient DNA obtained before operation and DNA from the graft obtained two to ten months after transplantation revealed the genotype of cells and showed only recipient cells in the graft area. Rather than preserve the viability of donor cells, a technique is required which will facilitate the introduction of recipient cells into patellar tendon allografts.

Adult↗

PubMed2002

The effect of a disrupted yhjQ gene on cellular morphology and cell growth in Escherichia coli.

The 5' upstream region of the cellulose synthase operon ( bcs operon) has been isolated by cloning from Escherichia coli. A gene encoding YhjQ is located 1.0 kb upstream of the bcs operon in E. coli. The function of YhjQ remains unknown. Insertional inactivation of the yhjQ gene causes abnormal cell division, resulting in incomplete partition of the chromosome and filamentous cells of various sizes. These results suggest that the product of yhjQ may affect normal doubling and cellular morphology.

Cell Cycle↗

PubMed2001

Effects of ageing and arthritic disease on nitric oxide production by human articular chondrocytes.

Nitric oxide (NO) has been considered as an important mediator in inflammatory phases and in loss of cartilage. In inflammatory arthritis, NO levels are correlated with disease activity and articular cartilage is able to produce large amounts of NO with the appropriate inducing factor such as cytokines. The old animals are shown to have a greater sensitivity to NO than young animals. This study evaluated the basal production of NO in normal and OA-affected chondroyctes from young and old patients and compared the levels of NO formation in response to IL-1beta. The results showed that the basal levels were 7-fold higher in old chondrocytes than those of young cells. However, the IL-1beta induced NO production was seen to decrease with age. Aminoguianidine (AG), a competitive inhibitor of iNOS, inhibited NO formation completely in both chondrocytes from young and old individuals. However, at the same concentration of AG it caused partial inhibition of NO and iNOS formation in chondrocytes from OA-affected individuals. In addition, although the IL-1beta induced NO production was much lesser than that of young chondrocytes, the inhibition of collagen production by IL-1beta was prominent in old chondrocytes and OA-affected chondrocytes. These results suggest that age-related differences in the regulation of NO production and collagen production, which may affect the ageing cells and osteoarthritic changes in some way.

Aging↗

PubMed2001

Cloning and characterization of an intracellular isoamylase gene from Pectobacterium chrysanthemi PY35.

The gene encoding an intracellular isoamylase from the Pectobacterium chrysanthemi PY35 was cloned in Escherichia coli DH5alpha and sequenced. The isoamylase gene (amyX) had an open reading frame of 1974 bp encoding 657 amino acid residues with a calculated molecular weight of 74,151 Da. The molecular weight of the enzyme was also estimated to be 74 kDa by activity staining of a SDS-PA gel. Isoamylase from P. chrysanthemi PY35 had 59% pairwise amino acid identity with glycogen debranching enzyme from E. coli and contained the four regions conserved among all amylolytic enzymes. The isoamylase was optimally active at pH 7 and 40 degrees C. AmyX hydrolyzed alpha-1,6-glycosidic linkages of amylopectin, while did not hydrolyze alpha-1,4-glycosidic linkages of amylose.

Amino Acid Sequence↗

PubMed2001

Superheating and supercooling of vortex matter in a Nb single crystal: direct evidence for a phase transition at the peak effect from neutron diffraction.

We report the first observation of a striking history dependence of the structure function of vortex matter in the peak effect regime in a Nb single crystal by using small angle neutron scattering combined with in situ magnetic susceptibility measurements. Metastable phases of vortex matter, supercooled vortex liquid and superheated vortex solid, have been identified. We interpret our results as direct structural evidence for a first-order vortex solid-liquid transition at the peak effect.

Journal Article↗

PubMed2001

Smad3 and Smad4 mediate transforming growth factor-beta1-induced IgA expression in murine B lymphocytes.

Transforming growth factor (TGF)-beta1 is well established as a critical IgA isotype switching factor and Smad molecules have been reported to act as transducers and transcriptional factors in the expression of TGF-beta1-targeted genes. We examined the involvement of Smad proteins in TGF-beta1-induced IgA expression. First, we found that TGF-beta1 significantly increases endogenous germ-line (GL) alpha transcripts by LPS-stimulated CH12.LX.4933 (mu(+)) B lymphoma cells. To investigate its signaling mechanisms, the lymphoma cell line was transfected with pFL3 that contains the TGF-beta-responsive element of the GLalpha promoter, and stimulated with TGF-beta1. Similar to endogenous GLalpha transcripts, TGF-beta1 induces GLalpha promoter activity and overexpression of Smad3 markedly enhances the promoter activity. This activity is further augmented by cotransfected Smad4. On the other hand, Smad7 substantially abrogates the synergistic effect of Smad3/4 onGLalpha promoter activity. In addition, overexpression of Smad3/4 enhances TGF-beta1-induced endogenous GLalpha transcripts in normal spleen B cells. Finally, in the presence of TGF-beta1, overexpression of Smad3/4 selectively increases both surface IgA expression and IgA production. The results from the present study indicate that Smad3, Smad4, and Smad7, at least in part, serve as mediators linking TGF-beta1 to transcriptional regulation of IgA switching related gene and regulation of IgA class switching.

Animals↗

PubMed2001

Cloning of the cel9A gene and characterization of its gene product from marine bacterium Pseudomonas sp. SK38.

The yellow-pigmented bacterial strain causing green spot rot and death of layer was isolated from Porphyra dentata. This strain has been identified as Pseudomonas sp., harboring agarase, xylanase, and protease activity, as well as carboxymethyl-cellulase (CMCase). Using genomic DNA from the Pseudomonas sp. SK38 digested with Sau3AI and ligated into pBluescript II KS+, we isolated a cel gene encoding a CMCase in Pseudomonas sp. SK38. A 4.5-kb fragment was subcloned into pKR400. The structure of the cel9A gene consists of an open reading frame of 1,521 bp starting with a GTG start codon and ending with a TAG stop codon. It thus encodes 506 amino acid residues of a protein with a calculated molecular weight of 52,636 daltons plus a signal peptide of 22 amino acids. The deduced amino acid sequence of the cel9A protein is similar to the same protein of Clostridium thermocellum. It contains, in particular, the two conserved regions of the glycoside hydrolase family 9. The apparent molecular mass of the Cel9A protein is 52 kDa as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme is most active at pH 6-7 and an optimal temperature of around 30 degrees C.

Amino Acid Sequence↗

PubMed2001

Helicobacter sp. recovered from drinking water biofilm sampled from a water distribution system.

Workers examining the transmission route(s) and reservoir(s) of infection for Helicobacter pylori have postulated several environmental reservoirs for the organism, including water. Such work has, to date, concentrated on the bulk liquid in drinking water systems rather than on biofilms. Previous investigations by the authors have suggested biofilms in water distribution systems are a possible reservoir of infection. This current study comprised of an analysis of a section of cast iron mains distribution pipe removed from an urban environment in the north-east of Scotland during routine maintenance work. Immediately upon removal of the pipe section, the interior lumen was swabbed to remove the biofilm layer. Subsequent analysis for the presence of Helicobacter DNA using a nested PCR approach produced a positive result. This data provides the first evidence for the existence of Helicobacter in biofilms found in water distribution systems anywhere in the world.

Biofilms↗

PubMed2001

Roles of Ets proteins, NF-kappa B and nocodazole in regulating induction of transcription of mouse germline Ig alpha RNA by transforming growth factor-beta 1.

Antibody class switch recombination (CSR) occurs after antigen activation of B cells. CSR is directed to specific heavy chain isotypes by cytokines and B cell activators that induce transcription from the unrearranged, or germline (GL), C(H) region genes. Transforming growth factor (TGF)-beta1 is essential for switch recombination to IgA due to its ability to induce transcription from GL Ig alpha genes. It has been shown that the promoters which regulate transcription of mouse and human GL alpha RNAs contain a TGF-beta1-responsive element that binds Smad and core binding factor (CBFalpha)/AML/PEBPalpha/RUNX: They also contain other elements which bind the transcription factors CREB, BSAP and Ets family proteins. In this manuscript we demonstrate that two tandem Ets sites in the mouse GL alpha promoter bind the transcription factors Elf-1 and PU.1, and that the 3' site is essential for expression of a luciferase reporter gene driven by the GL alpha promoter. Binding of Elf-1 to the GL alpha promoter is inducible by lipopolysaccharide in nuclear extracts from splenic B cells. An NF-kappaB site is identified, although it does not contribute to expression of the promoter in reporter gene assays. Since CSR to IgA is greatly reduced in NF-kappaB/p50-deficient mice, these data support the hypothesis that NF-kappaB has roles in switching in addition to regulation of GL transcription. Finally, we demonstrate that nocodazole, which disrupts microtubules that sequester Smad proteins in the cytoplasm, stimulates transcription from the GL alpha promoter.

Animals↗

PubMed2001

Hypoglycemic activity of the fruit of the Momordica charantia in type 2 diabetic mice.

The antidiabetic activity of Momordica charantia L. (Cucurbitaceae) was investigated in KK-Ay mice, an animal model with type 2 diabetes with hyperinsulinemia. The water extract of the fruit of Momordica charantia L. (MC) reduced the blood glucose of KK-Ay mice 3 weeks after oral administration (p<0.01) and also significantly lowered the serum insulin of KK-Ay mice under similar conditions (p<0.01). However, MC did not affect the blood glucose in normal mice. MC-treated KK-Ay mice blood glucose significantly decreased in an insulin tolerance test. Moreover, the muscle content of facilitative glucose transporter isoform 4 (GLUT4) protein content in the plasma membrane fraction from muscle significantly increased in the orally MC-treated mice when compared with that of the controls (p<0.01). These results suggest that the antidiabetic effect of MC is derived, at least in part, from a decrease in insulin resistance because of the increase of GLUT4 protein content in the plasma membrane of the muscle.

Administration, Oral↗

PubMed2000

Cloning and characterization of thermostable endoglucanase (Cel8Y) from the hyperthermophilic Aquifex aeolicus VF5.

Aquifex aeolicus is the hyperthermophilic bacterium known, with growth-temperature maxima near 95 degrees C. The cel8Y gene, encoding a thermostable endoglucanase (Cel8Y) from Aquifex aeolicus VF5, was cloned into a vector for expression and expressed in Escherichia coli XL1-Blue. A clone of 1.7 kb fragment containing endoglucanase activity, designated pKYCY100, was sequenced and found to contain an ORF of 978 bp encoding a protein of 325 amino acid residues, with a calculated molecular mass of 38,831 Da. This endoglucanase was designated cel8Y gene. The endoglucanase has an 18-amino-acid signal peptide but not cellulose-binding domain. The endoglucanase of A. aeolicus VF5 had significant amino acid sequence similarities with endoglucanases from glycosyl hydrolase family 8. The predicted amino acid sequence of the Cel8Y protein was similar to that of CMCase of Cellulomonas uda, BcsC of Escherichia coli, CelY of Erwinia chrysanthemi, and CMCase of Acetobacter xylinum. The molecular mass of Cel8Y was calculated to be 36,750 Da, which is consistent with the value obtained from result of CMC-SDS-PAGE of the purified enzyme. Cel8Y was thermostable, exhibiting maximal activity at 80 degrees C and pH optima of 7.0 and with half-lives of 2 h at 100 degrees C, 4 h at 90 degrees C.

Amino Acid Sequence↗

PubMed2000

Cloning and sequencing of cel5Z gene from Erwinia chrysanthemi PY35.

The phytopathogenic bacterium Erwinia chrysanthemi (Ech) secretes multiple isozymes of plant cell wall disrupting enzymes such as pectate lyase and endoglucanases. We cloned genomic DNA from Ech PY35 digested with Sau3AI and ligated into pBluescript II SK+. One of the E. coli XL1-blue clones had the ability to hydrolyze carboxymethyl cellulose and polygalacturonic acid. By subsequent subcloning from this 2.9 kb fragment, we obtained a 2.0 kb (pPY401), designated cel5Z, which had the activity of hydrolyzation of carboxymethyl cellulose. The cel5Z gene had an open reading frame (ORF) of 1,281 bp starting with an ATG start codon and followed by a TAA stop codon, encoding 426 amino acids with a signal peptide of 41 amino acids. Since the deduced amino acid sequence of this protein was very similar to that of CelE of Pseudomonas fluorescens, and had the conserved region, VIYEIYNEPL, it belonged to the glycoside hydrolase family 5 of EC 3.2.1.4. The molecular mass of Cel5Z protein from E. coli XL1-blue, as analyzed by CMC-SDS-PAGE, appeared to be 42 kDa. The optimum pH was 6, and the optimum temperature was about 40 degrees C for its enzymatic activity.

Amino Acid Sequence↗

PubMed2000

Characterization of Erwinia chrysanthemi PY35 cel and pel gene existing in tandem and rapid identification of their gene products.

Genomic DNA of the phytopathogenic Erwinia chrysanthemi PY35 was partially digested with Sau3AI, ligated into the BamHI site of pBluescript II SK+, and introduced into E. coli. One clone that was able to hydrolyse carboxymethylcellulose and polygalacturonic acid was selected. A 2.9 kb fragment containing the pelL1 gene (pPY300) and cel5Z gene (pPY401) in tandem was subcloned and sequenced. The pelL1 and cel5Z genes had open reading frames of 1,278 bp and 1,281 bp encoding 425 and 426 amino acid residues with calculated molecular weights of 45,649 Da and 46,473 Da, respectively. pelL1 and cel5Z carried a typical prokaryotic signal peptide of 24 and 41 amino acid residues, respectively. The apparent molecular masses of the proteins when expressed in E. coli cells were approximately 43 kDa (PelL1) and 42 kDa (Cel5Z) as assessed by PGA-SDS-PAGE and CMC-SDS-PAGE.

Amino Acid Sequence↗

PubMed2000

Cloning and sequencing of pel gene responsible for CMCase activity from Erwinia chrysanthemi PY35.

The phytopathogenic bacterium Erwinia chrysanthemi secretes multiple isozymes of plant cell wall disrupting enzymes such as pectate lyase and endoglucanase. We cloned genomic DNA from Erwinia chrysanthemi PY35. One of the E. coli XL1-Blue clones contained a 5.1-kb BamHI fragment and hydrolyzed carboxymethyl cellulose and polygalacturonic acid. By subsequent subcloning, we obtained a 2.9-kb fragment (pPY100) that contained the pel gene responsible for CMCase and pectate lyase activities. The pel gene had an open reading frame (ORF) of 1,278 bp encoding 425 amino acids with a signal peptide of 25 amino acids. Since the deduced amino acid sequence of this protein was very similar to that of PelL of E. chrysanthemi EC16, we concluded that it belonged to the pectate lyase family EC 4.2.2.2, and we designated it PelL1. Sequencing showed that the PeIL1 protein contains 400 amino acids and has a calculated pI of 7.15 and a molecular mass of 42,925 Da. The molecular mass of PelL1 protein expressed in E. coli XL1-Blue, as analyzed by SDS-PAGE, appeared to be 43 kDa. The optimum pH for its enzymatic activity was 9, and the optimum temperature was about 40 decreased C.

Amino Acid Sequence↗

PubMed1999

Interconversion potential of cloned human marrow adipocytes in vitro.

Information on the interconversion potential of adipocytes and other end cells characteristic of the stromal fibroblastic cell lineages, key in the understanding of bone turnover in metabolic diseases such as osteoporosis, is limited. The object of the present study was: i) to isolate relatively pure populations of adipocytes from human bone marrow; ii) to clone single adipocytes from these populations; and iii) to examine in vitro the interconversion potential of the progeny of these single-cloned adipocytes between the osteogenic and adipogenic phenotypes. Adipogenic colonies were isolated from the low-density floating fraction of normal bone marrow cells cultured in adipogenic media for 4 days. Single adipocytes were isolated and cloned by limiting dilution. Cloned adipocytes were found to dedifferentiate into fibroblast-like cells, and subsequently to differentiate into two morphologically distinct cell types: osteoblasts and adipocytes in appropriate culture systems. The adipocytic phenotype was confirmed by morphology, oil red O staining, and immunocytochemistry using antiserum to aP2. The osteogenic phenotype was confirmed by alkaline phosphatase, osteocalcin immunostaining using specific osteocalcin antiserum, and formation of mineralized cell aggregates. These findings demonstrate the extent of plasticity between the differentiation of adipocytic and osteogenic cells in human bone marrow stromal cell cultures. We have shown the ability of isolated clonal adipogenic cells to redifferentiate into cells of the osteogenic and adipogenic lineage and the interconversion potential of human marrow stromal cells in vitro. These results provide further evidence that the osteogenic and adipogenic cells share a common multipotential precursor.

Adipocytes↗