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Biomedical subjects

S Park

Publications and source records attributed to S Park.

At least 91 records · Page 5Linked to original sources
PubMed2003

Varicella-zoster viral meningitis mimicking lymphoma.

We report the case of a 30-year-old HIV-infected man admitted for a meningeal syndrome and a zoster rash. The CSF had cytological features suggesting a primary CNS lymphoma (PCNSL). The large lymphoid cells had a fine chromatin with nucleoli, a basophilic cytoplasm with azurophilic granules and high mitotic activity. Several arguments demonstrated the viral origin of the meningitis: the large lymphoid cells were of T origin with no evidence of clonal TCR gamma gene rearrangement. The PCR was positive for Varicella-Zoster Virus (VZV) and EBV DNA. Clinical evolution was favorable under acyclovir. We should be cautious in the differential diagnosis between viral meningitis and PCNSL.

Adult↗
PubMed2003

Pancreatic stellate cell activation by ethanol and acetaldehyde: is it mediated by the mitogen-activated protein kinase signaling pathway?

BACKGROUND: Pancreatic fibrosis is a characteristic feature of alcoholic chronic pancreatitis. Recent studies suggest that activated pancreatic stellate cells (PSCs) are the major cell-type involved in pancreatic fibrogenesis. Cultured PSCs become activated when exposed to ethanol or its metabolite acetaldehyde (as indicated by increased alpha-smooth muscle actin [alpha-SMA] expression and increased collagen synthesis). However the intracellular signaling mechanisms responsible for ethanol- or acetaldehyde-induced PSC activation remain to be fully elucidated. One of the major signaling pathways known to regulate protein synthesis in mammalian cells is the mitogen-activated protein kinase (MARK) pathway. AIMS: To examine the effects of ethanol and acetaldehyde on the MAPK pathway (by assessing the activities of the 3 major subfamilies (extracellular-regulated kinases 1 and 2 [ERK 1/2], JNK and p38 kinase) in PSCs and to examine the role of p38 kinase in mediating the ethanol- and acetaldehyde-induced increase in alpha-SMA expression in activated rat PSCs. METHODS: Rat PSCs were incubated with ethanol (50 mM) or acetaldehyde (200 microM) for 15 min, 30 min, 60 min, and 24 h; and activities of ERK 1/2, JNK, and p38 kinase were assessed in cell lysates using kinase assays and Western blot. In addition, rat PSCs were treated with the specific p38 MAPK inhibitor SB203580 in the presence or absence of ethanol or acetaldehyde for 24h, and activation of the downstream protein kinase MAPKAP kinase-2 (an indicator of p38 MAPK activity) was assessed by Western blot. Specific inhibitors were also used to inhibit the activity of ERK 1/2 and JNK. Following inhibition of the above signaling pathways, alpha-SMA expression by PSCs was assessed by Western blot. RESULTS: Ethanol and acetaldehyde increased the activation of all 3 subfamilies (ERK 1/2, JNK and p38 kinase) of the MAPK pathway in PSCs. Treatment of PSCs with SB203580 abolished the ethanol- and acetaldehyde-induced increase in p38 MAPK activity and also prevented the induction of alpha-SMA expression in PSCs. However, inhibition of ERK 1/2 and JNK had no effect on ethanoland acetaldehyde-induced alpha-SMA expression in PSCs. CONCLUSIONS: (1) The MAP kinase pathway is induced in PSCs after exposure to ethanol or acetaldehyde and this induction is sustained for at least 24h. (2) The p38 MAPK pathway mediates the activation (as indicated by increased alpha-SMA expression) of PSCs by ethanol or acetaldehyde.

Acetaldehyde↗
PubMed2003

Rat pancreatic stellate cells secrete matrix metalloproteinases: implications for extracellular matrix turnover.

BACKGROUND: Pancreatic fibrosis is a characteristic feature of chronic pancreatic injury and is thought to result from a change in the balance between synthesis and degradation of extracellular matrix (ECM) proteins. Recent studies suggest that activated pancreatic stellate cells (PSCs) play a central role in pancreatic fibrogenesis via increased synthesis of ECM proteins. However, the role of these cells in ECM protein degradation has not been fully elucidated. AIMS: To determine: (i) whether PSCs secrete matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) and, if so (ii) whether MMP and TIMP secretion by PSCs is altered in response to known PSC activating factors such as tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta1 (TGF-beta1), interleukin 6 (IL-6), ethanol, and acetaldehyde. METHODS: Cultured rat PSCs (n=3-5 separate cell preparations) were incubated at 37 degrees C for 24 hours with serum free culture medium containing TNF-alpha (5-25 U/ml), TGF-beta1 (0.5-1 ng/ml), IL-6 (0.001-10 ng/ml), ethanol (10-50 mM), or acetaldehyde (150-200 micro M), or no additions (controls). Medium from control cells was examined for the presence of MMPs by zymography using a 10% polyacrylamide-0.1% gelatin gel. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine gene expression of MMP9 and the tissue inhibitors of metalloproteinases TIMP1 and TIMP2. Western blotting was used to identify a specific MMP, MMP2 (a gelatinase that digests basement membrane collagen and the dominant MMP observed on zymography) and a specific TIMP, TIMP2. Reverse zymography was used to examine functional TIMPs in PSC secretions. The effect of TNF-alpha, TGF-beta1, and IL-6 on MMP2 secretion was assessed by densitometry of western blots. The effect of ethanol and acetaldehyde on MMP2 and TIMP2 secretion was also assessed by this method. RESULTS: Zymography revealed that PSCs secrete a number of MMPs including proteinases with molecular weights consistent with MMP2, MMP9, and MMP13. RT-PCR demonstrated the presence of mRNA for metalloproteinase inhibitors TIMP1 and TIMP2 in PSCs while reverse zymography revealed the presence of functional TIMP2 in PSC secretions. MMP2 secretion by PSCs was significantly increased by TGF-beta1 and IL-6, but was not affected by TNF-alpha. Ethanol and acetaldehyde induced secretion of both MMP2 and TIMP2 by PSCs. CONCLUSIONS: Pancreatic stellate cells have the capacity to synthesise a number of matrix metalloproteinases, including MMP2, MMP9, and MMP13 and their inhibitors TIMP1 and TIMP2. MMP2 secretion by PSCs is significantly increased on exposure to the proinflammatory cytokines TGF-beta1 and IL-6. Both ethanol and its metabolite acetaldehyde increase MMP2 as well as TIMP2 secretion by PSCs. IMPLICATION: The role of pancreatic stellate cells in extracellular matrix formation and fibrogenesis may be related to their capacity to regulate the degradation as well as the synthesis of extracellular matrix proteins.

Acetaldehyde↗
PubMed2003

Cell migration: a novel aspect of pancreatic stellate cell biology.

BACKGROUND: Pancreatic stellate cells (PSCs), implicated as key mediators of pancreatic fibrogenesis, are found in increased numbers in areas of pancreatic injury. This increase in PSC number may be due to increased local proliferation and/or migration of these cells from adjacent areas. The ability of PSCs to proliferate has been well established but their potential for migration has not been examined. AIMS: Therefore, the aims of this study were to determine whether cultured rat PSCs have the capacity to migrate and, if so, to characterise this migratory capacity with respect to the influence of basement membrane components and the effect of platelet derived growth factor (PDGF, a known stimulant for migration of other cell types). METHODS: Migration of freshly isolated (quiescent) and culture activated (passaged) rat PSCs was assessed across uncoated or Matrigel (a basement membrane-like substance) coated porous membranes (pore size 8 micro m) in the presence or absence of PDGF (10 and 20 ng/ml) in the culture medium. A checkerboard assay was performed to assess whether the effect of PDGF on PSC migration was chemotactic or chemokinetic. RESULTS: Cell migration was observed with both freshly isolated and passaged PSCs. However, compared with passaged (culture activated) cells, migration of freshly isolated cells was delayed, occurring only at or after 48 hours of incubation when the cells displayed an activated phenotype. PSC migration through Matrigel coated membranes was delayed but not prevented by basement membrane components. PSC migration was increased by PDGF and this effect was predominantly chemotactic (that is, in the direction of a positive concentration gradient). CONCLUSIONS: (i) PSCs have the capacity to migrate. (ii) Activation of PSCs appears to be a prerequisite for migration. (iii) PDGF stimulates PSC migration and this effect is predominantly chemotactic. IMPLICATION: Chemotactic factors released during pancreatic injury may stimulate the migration of PSCs through surrounding basement membrane towards affected areas of the gland.

Animals↗
PubMed2002

Hydrogen-bonded silica gels dispersed in a smectic liquid crystal: a random field XY system.

The effect on the nematic to smectic-A transition in octylcyanobiphenyl (8CB) due to dispersions of hydrogen-bonded silica (aerosil) particles is characterized with high-resolution x-ray scattering. The particles form weak gels in 8CB creating a quenched disorder that replaces the transition with the growth of short-range smectic correlations. The correlations include thermal critical fluctuations that dominate at high temperatures and a second contribution that quantitatively matches the static fluctuations of a random field system and becomes important at low temperatures.

Journal Article↗
PubMed2002

Erythroleukemia: a need for a new definition.

The new WHO classification abolishes the frontier between RAEB-t with 20% of blasts and leukemia with 30% of blasts. We review the definitions of erythroleukemia and discuss the relationship between FAB AML6, RAEB-t and AML6 variant. We ask whether secondary erythroleukemias are the same entity as RAEB-t on survival, karyotype and cytologic characteristics. We suggest that 'AML6 variant' with pure erythroid lineage proliferation would be the real de novo erythroleukemia. Current FAB AML6 entity will probably be classified in either subgroup (1) multilineage dysplasia; (2) therapy-related leukemia; or (3) acute erythroid leukemia subdivided into erythroleukemia (erythroid/myeloid) and pure erythroid leukemia, in the WHO classification - a classification which highlights the importance of clinical and cytogenetic prognostic factors.

Adolescent↗
PubMed2002

PCR-RFLP analysis of Giardia intestinalis using a Giardia-specific gene, GLORF-C4.

A cDNA clone encoding GLORF-C4 was isolated from the WB strain, an assemblage A Giardia intestinalis. Interestingly, GLORF-C4 has been previously reported as an assemblage B-specific gene. Using two primers based on GLORF-C4 of the GS strain, a prototype assemblage B, GLORF-C4 gene was amplified from all the groups of G. intestinalis, and applied to detect the presence of cysts of G. intestinalis from faecal samples of cyst-passers. RFLP analysis of this PCR product successfully classified G. intestinalis into two distinct groups, assemblages A and B.

Animals↗
PubMed2002

Physicochemical characterization of UASB sludge with different size distributions.

Upflow anaerobic sludge blanket (UASB) sludges developed in UASB system are used to treat various wastewaters. Methanogenic microbial consortia in UASB sludges convert organic compounds to methane under anaerobic conditions. Sludge granules are developed by self-granulation of microorganisms and dynamic balance between granule growth and decay results in coexistence of UASB sludges with different sizes in the reactor. In this study, UASB sludges taken from a laboratory-scale UASB reactor were classified into 4 groups based on their diameters and their physicochemical characteristics were investigated. Each group was analyzed for settling ability, specific methanogenic activity (SMA), and elemental content. Settling ability was proportional to diameter of UASB sludges, suggesting effective detainment of larger granular sludges in the reactor. When acetate o r glucose was used as a substrate, a ll groups showed a relatively slight difference in SMA. However SMA with a volatile fatty acid mixture showed a significant increase with sludge diameter, suggesting better establishment of syntrophic relationship in larger granular sludges. Larger granular sludges showed a higher value of SMA upon environmental changes(ie., pH, temperature, or toxicant concentration). Comparative analysis of elemental contents showed that content (dry weight %) of most tested elements (Fe, Ca, P, Zn, Ni, and Mn) decreased with sludge diameter, suggesting that the elements could be important for initial granulation. Taken together, this study verified experimentally that physicochemical properties of UASB sludges are related to UASB sludge size distributions. Overall results of physicochemical characterization supports that larger granular sludges are better applicable to UASB systems.

Bacteria, Anaerobic↗
PubMed2002

A survey of practice preferences and attitudes to the New Zealand Guidelines for the Management of Heavy Menstrual Bleeding.

OBJECTIVE: To survey the practice preferences and the attitudes of New Zealand gynaecologists, general practitioners and family planning doctors to Guidelines for the Management of Heavy Menstrual Bleeding. STUDY DESIGN: A postal survey collected information on the following: demographics, practice preferences, knowledge of, usage of and attitudes toward the Guidelines for the Management of Heavy Menstrual Bleeding. The survey was sent to randomly selected practising general practitioners (n = 531), all specialist gynaecologists (n = 194) and all Family Planning Association doctors (n = 69) in New Zealand. Replies were received from 441 (56%). RESULTS: The preferred first choice for the management of heavy menstrual bleeding by general practitioners and family planning doctors was nonsteroidal anti-inflammatory medications (23%). Tranexamic acid was the preferred first choice medication for the management of heavy menstrual bleeding by specialists (57%), and preferred second choice (as well as levonorgestrel intrauterine system) by general practitioners and family planning doctors (34%). Barriers identified by general practitioners and family planning doctors to implementing the guideline included inability to access ultrasound scanning and specialist services, and a lack of subsidy for tranexamic acid and the levonorgestrel intrauterine system. CONCLUSIONS: There has been a change in prescribing patterns since 1995 among specialist and general practitioners and family planning doctors in New Zealand in accordance with the Guidelines for the Management of Heavy Menstrual Bleeding. Further attention to reducing barriers should focus on increasing access to ultrasound scanning, specialist services and subsidising the levonorgestrel intrauterine system.

Adult↗
PubMed2002

Efficacy of orally delivered cochleates containing amphotericin B in a murine model of aspergillosis.

Cochleates containing amphotericin B (CAMB) were administered orally at doses ranging from 0 to 40 mg/kg of body weight/day for 14 days in a murine model of systemic aspergillosis. The administration of oral doses of CAMB (20 and 40 mg/kg/day) resulted in a survival rate of 70% and a reduction in colony counts of more than 2 logs in lungs, livers, and kidneys. Orally administered CAMB shows promise for the treatment of aspergillosis.

Amphotericin B↗
PubMed2001

Improved preparation and use of room-temperature ionic liquids in lipase-catalyzed enantio- and regioselective acylations.

Polar organic solvents such as methanol or N-methylformamide inactivate lipases. Although ionic liquids such as 3-alkyl-1-methylimidazolium tetrafluoroborates have polarities similar to these polar organic solvents, they do not inactivate lipases. To get reliable lipase-catalyzed reactions in ionic liquids, we modified their preparation by adding a wash with aqueous sodium carbonate. Lipase-catalyzed reactions that previously did not occur in untreated ionic liquids now occur at rates comparable to those in nonpolar organic solvents such as toluene. Acetylation of 1-phenylethanol catalyzed by lipase from Pseudomonas cepacia (PCL) was as fast and as enantioselective in ionic liquids as in toluene. Ionic liquids permit reactions in a more polar solvent than previously possible. Acetylation of glucose catalyzed by lipase B from Candida antarctica (CAL-B) was more regioselective in ionic liquids because glucose is up to one hundred times more soluble in ionic liquids. Acetylation of insoluble glucose in organic solvents yielded the more soluble 6-O-acetyl glucose, which underwent further acetylation to give 3,6-O-diacetyl glucose (2-3:1 mixture). However, acetylation of glucose in ionic liquids yielded only 6-O-acetyl glucose (>13:1 and up to >50:1).

Acylation↗
PubMed2001

Crystal structure of the anthrax lethal factor.

Lethal factor (LF) is a protein (relative molecular mass 90,000) that is critical in the pathogenesis of anthrax. It is a highly specific protease that cleaves members of the mitogen-activated protein kinase kinase (MAPKK) family near to their amino termini, leading to the inhibition of one or more signalling pathways. Here we describe the crystal structure of LF and its complex with the N terminus of MAPKK-2. LF comprises four domains: domain I binds the membrane-translocating component of anthrax toxin, the protective antigen (PA); domains II, III and IV together create a long deep groove that holds the 16-residue N-terminal tail of MAPKK-2 before cleavage. Domain II resembles the ADP-ribosylating toxin from Bacillus cereus, but the active site has been mutated and recruited to augment substrate recognition. Domain III is inserted into domain II, and seems to have arisen from a repeated duplication of a structural element of domain II. Domain IV is distantly related to the zinc metalloprotease family, and contains the catalytic centre; it also resembles domain I. The structure thus reveals a protein that has evolved through a process of gene duplication, mutation and fusion, into an enzyme with high and unusual specificity.

Amino Acid Sequence↗
PubMed2001

Structural study of novel antimicrobial peptides, nigrocins, isolated from Rana nigromaculata.

Novel cationic antimicrobial peptides, named nigrocin 1 and 2, were isolated from the skin of Rana nigromaculata and their amino acid sequences were determined. These peptides manifested a broad spectrum of antimicrobial activity against various microorganisms with different specificity. By primary structural analysis, it was revealed that nigrocin 1 has high sequence homology with brevinin 2 but nigrocin 2 has low sequence homology with any other known antimicrobial peptides. To investigate the structure-activity relationship of nigrocin 2, which has a unique primary structure, circular dichroism (CD) and homonuclear nuclear magnetic resonance spectroscopy (NMR) studies were performed. CD investigation revealed that nigrocin 2 adopts mainly an alpha-helical structure in trifluoroethanol (TFE)/H(2)O solution, sodium dodecyl sulfate (SDS) micelles, and dodecylphosphocholine micelles. The solution structures of nigrocin 2 in TFE/H(2)O (1:1, v/v) solution and in SDS micelles were determined by homonuclear NMR. Nigrocin 2 consists of a typical amphipathic alpha-helix spanning residues 3-18 in both 50% TFE solution and SDS micelles. From the structural comparison of nigrocin 2 with other known antimicrobial peptides, nigrocin 2 could be classified into the family of antimicrobial peptides containing a single linear amphipathic alpha-helix that potentially disrupts membrane integrity, which would result in cell death.

Amino Acid Sequence↗
PubMed2001

Stimulation of ERK2 by taurine with enhanced alkaline phosphatase activity and collagen synthesis in osteoblast-like UMR-106 cells.

Taurine is present in a variety of tissues and exhibits many important physiological functions in the cell. Even though its functions are well documented in many tissues, its actions on bone cells are largely unknown. Considering a recent finding that taurine is present in the bone, we wished to determine if taurine could have any effects on osteoblast cells. Taurine (10 mM) stimulated alkaline phosphatase activity as well as collagen synthesis. Taurine also stimulated tyrosine phosphorylation of a number of cellular proteins including a 42-kDa protein. The 42-kDa protein was identified as extracellular signal regulated protein kinase 2 (ERK2). A mitogen-activated protein kinase kinase (MEK) inhibitor blocked the taurine-stimulated alkaline phosphatase activity and collagen synthesis. These results suggest that taurine could regulate osteoblast metabolism via ERK2 activation.

Alkaline Phosphatase↗
PubMed2001

Structural characterization of beta-cardiac myosin subfragment 1 in solution.

beta-cardiac myosin subfragment 1 (betaS1) tertiary structure and dynamics were characterized with proteolytic digestion, nucleotide analogue trapping kinetics, and intrinsic fluorescence changes accompanying nucleotide binding. Proteolysis of betaS1 produces the 25, 50, and 20 kDa fragments and a new cut within the 50-kDa fragment at Arg369. F-actin inhibits cleavage of the 50-kDa fragment and fails to inhibit cleavage at the 50/20 kDa junction, suggesting betaS1 presents an actoS1 conformation fundamentally different from skeletal S1. Time-dependent changes in Mg(2+)-ATPase accompanying proteolysis identifies cleavage points that lie within the energy transduction pathway. The nucleotide analogue trapping kinetics reveal the presence of a reversible weakly actin attached state. Comparison of nucleotide analogue induced betaS1 structures with the transient structures occurring during ATPase indicates analogue induced and transient structures are in a one-to-one correspondence. Tryptophan fluorescence enhancement accompanies the binding or trapping of nucleotide or nucleotide analogues. Isolation of Trp508 fluorescence shows it is an ATP-sensitive tryptophan and that its vicinity changes conformation sequentially with the transient intermediates accompanying ATPase. These studies elucidate energy transduction and suggest how mutations of betaS1 implicated in disease might undermine function, stability, or efficiency.

Adenosine Triphosphatases↗
PubMed2001

Liquid chromatography at the critical condition for polyisoprene using a single solvent.

Liquid chromatography at the chromatographic critical condition has drawn much attention as an attractive characterization method of block copolymers since it has been proposed that a part of a polymer chain becomes "chromatographically invisible" at this condition, which would permit the characterization of individual blocks. A critical condition for a polymer species has been commonly established by use of mixed-solvent systems. It is not easy, however, to reproduce the critical condition since the retention of polymers depends very sensitively on the solvent composition and purity. Furthermore, the preferential sorption of a component in a mixed solvent may cause an additional problem. Therefore, the use of a single solvent is highly desirable to improve the reproducibility as well as the repeatability. In this study, a single-solvent critical condition for polyisoprene was established with 1,4-dioxane and C18 bonded silica as the mobile and stationary phases, respectively. At this condition, the "chromatographic invisibility" of polystyrene-polyisoprene diblock copolymers was critically examined and it was found that a rigorous chromatographic invisibility was not achieved and the retention of the block copolymers was affected by the length of the blocks under the critical condition. Some other chromatographic applications using the single-solvent system are also reported.

Journal Article↗
PubMed2001

Prevalence of vaginal colonization by drug-resistant Candida species in college-age women with previous exposure to over-the-counter azole antifungals.

We enrolled 382 college-age women in a cross-sectional survey to investigate the relationship between use of over-the-counter (OTC) azole-based antifungal drugs and vaginal colonization by drug-resistant Candida. This study showed no correlation (P=.506) between previous OTC exposure and colonization of drug-resistant Candida in vaginal flora. However, a small number of resistant Candida species isolates were obtained from women with a history of multiple exposures to OTC antifungals; given the widespread use of these products, this may be an emerging concern.

Adult↗