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Biomedical subjects

J Park

Publications and source records attributed to J Park.

At least 91 records · Page 5Linked to original sources

Glutathione S-transferase mu modulates the stress-activated signals by suppressing apoptosis signal-regulating kinase 1.

Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that can activate the c-Jun N-terminal kinase and the p38 signaling pathways. It plays a critical role in cytokine- and stress-induced apoptosis. To further characterize the mechanism of the regulation of the ASK1 signal, we searched for ASK1-interacting proteins employing the yeast two-hybrid method. The yeast two-hybrid assay indicated that mouse glutathione S-transferase Mu 1-1 (mGSTM1-1), an enzyme involved in the metabolism of drugs and xenobiotics, interacted with ASK1. We subsequently confirmed that mGSTM1-1 physically associated with ASK1 both in vivo and in vitro. The in vitro binding assay indicated that the C-terminal portion of mGSTM1-1 and the N-terminal region of ASK1 were crucial for binding one another. Furthermore, mGSTM1-1 suppressed stress-stimulated ASK1 activity in cultured cells. mGSTM1-1 also blocked ASK1 oligomerization. The ASK1 inhibition by mGSTM1-1 occurred independently of the glutathione-conjugating activity of mGSTM1-1. Moreover, mGSTM1-1 repressed ASK1-dependent apoptotic cell death. Taken together, our findings suggest that mGSTM1-1 functions as an endogenous inhibitor of ASK1. This highlights a novel function for mGSTM1-1 insofar as mGSTM1-1 may modulate stress-mediated signals by repressing ASK1, and this activity occurs independently of its well-known catalytic activity in intracellular glutathione metabolism.

Animals↗

A fully automatic evolutionary classification of protein folds: Dali Domain Dictionary version 3.

The Dali Domain Dictionary (http://www.ebi.ac.uk/dali/domain) is a numerical taxonomy of all known structures in the Protein Data Bank (PDB). The taxonomy is derived fully automatically from measurements of structural, functional and sequence similarities. Here, we report the extension of the classification to match the traditional four hierarchical levels corresponding to: (i) supersecondary structural motifs (attractors in fold space), (ii) the topology of globular domains (fold types), (iii) remote homologues (functional families) and (iv) homologues with sequence identity above 25% (sequence families). The computational definitions of attractors and functional families are new. In September 2000, the Dali classification contained 10 531 PDB entries comprising 17 101 chains, which were partitioned into five attractor regions, 1375 fold types, 2582 functional families and 3724 domain sequence families. Sequence families were further associated with 99 582 unique homologous sequences in the HSSP database, which increases the number of effectively known structures several-fold. The resulting database contains the description of protein domain architecture, the definition of structural neighbours around each known structure, the definition of structurally conserved cores and a comprehensive library of explicit multiple alignments of distantly related protein families.

Amino Acid Motifs↗

Correlation of hematopoietic progenitor cell count determined by the SE-automated hematology analyzer with CD34(+) cell count by flow cytometry in leukapheresis products.

The yield of stem cell collection after mobilization is crucial for autologous peripheral blood stem cell (PBSC) transplantation. Quantitative determinations of CD34(+) cells using flow cytometry or stem cell culture have been used, but these methods require much time, technical experience, and expensive reagents. The automated hematology analyzer (Sysmex SE-9000trade mark, TOA, Japan) equipped with the Immature Information (IMI) channel for immature myeloid cells can detect IMI(+) cells within 90 sec. Detection is made possible by the combination of a special reagent system and direct current/radiofrequency biosensors. We studied the relation of IMI(+) cells and variable cell counts with CD34(+) cell yield in autologous stem cell harvest. In a series of 32 patients (median age, 44 years; M:F = 11:21), 184 leukaphereses were performed after mobilization regimens with chemotherapy and G-CSF or G-CSF alone. Full blood cell counts were enumerated on peripheral blood (PB) samples taken prior to each leukapheresis. Mononuclear cell (MNC) and IMI(+) cell counts by automated hematology analyzer and flow cytometry based CD34(+) cell yield were measured on the harvested product. The relationship among PB white blood cells (WBC), PB monocytes, IMI(+) cells, MNC, and CD34(+) cell yield in a single leukapheresis was estimated by Pearson correlation analysis. PB WBC count showed no correlation with CD34(+) cell yield in a single leukapheresis (r = 0.02, P = 0.81). PB monocyte count showed a weak correlation (r = 0.21, P = 0.01) and MNC in harvest also showed a weak correlation (r = 0.36, P = 0.0001) with CD34(+) cell yield. In contrast, CD34(+) cell yield correlated well with IMI(+) cell count (r = 0.68, P = 0.0001), and data could be fitted by a linear regression equation, y = 0.330 + 0.974x. IMI(+) cell assay by the automated hematology analyzer correlated well with the CD34(+) cell yield in a mobilized autologous stem cell harvest. The IMI(+) cell count might be used as a simple and efficient indicator of blood stem cell mobilization and collection.

Adolescent↗

JNK phosphorylates the HSF1 transcriptional activation domain: role of JNK in the regulation of the heat shock response.

The role of c-Jun NH2-terminal kinase (JNK) signaling cascade in the stress-inducible phosphorylation of heat shock factor 1 (HSF1) was investigated using known agonists and antagonists of JNK. We showed that treatment of HeLa cells with MG132, a proteasome inhibitor and known INK activator, caused the transcriptional activation domain of HSF1 to be targeted and phosphorylated by JNK2 in vivo. Dose-response and time course studies of the effects of heat shock and anisomycin treatment showed a close correlation of the activation of JNK and hyperphosphorylation of HSF1. SB203580 inhibited INK at the 100 microM concentration and significantly reduced the amount of hyperphosphorylated HSF1 upon heat shock or anisomycin treatment. SB203580 and dominant-negative JNK suppress hsp70 promoter-driven reporter gene expression selectively at 45 degrees C but not at 42 degrees C heat stress, suggesting that JNK would be preferentially associated with the protective heat shock response against severe heat stress. The possibility that JNK-mediated phosphorylation of HSF1 may selectively stabilize the HSF1 protein and confers protection to cells under conditions of severe stress is discussed.

Animals↗

Apoptosis induced by progesterone in human ovarian cancer cell line SNU-840.

Progesterone has been used as an ingredient of anticancer drug for patients with ovarian carcinoma. However, the mechanism of anticancer effects by progesterone has not been understood. In this study, the effects of progesterone on ovarian cancer cells, SNU-840, were investigated. After the incubation with progesterone, the viability of the cells was evaluated by MTT assay. As a result, 45% of the cells were viable after 48 h of incubation with 100 microM progesterone. In addition, [(3)H]thymidine incorporation assay showed that the proliferation of the cells was completely inhibited by progesterone after 48 h of incubation at 100 microM concentration. Colorimetric TUNEL assay revealed the fragmentation of the chromosomal DNA, suggesting that the process of the cell death was apoptosis. The level of the p53 mRNA was determined by northern blotting assay, since many apoptosis processes are mediated by up-regulation of the p53 expression. The level of the p53 mRNA reached its maximum at 12 h and decreased after 24 h of incubation with progesterone. In conclusion, progesterone inhibits the proliferation and elicits apoptosis of SNU-840 cells. Also, it up-regulates the p53 mRNA transiently.

Apoptosis↗

Msx1 gene overexpression induces G1 phase cell arrest in human ovarian cancer cell line OVCAR3.

Recent evidence suggested an involvement of homeobox genes in tumorigenesis. Here we investigated whether one of homeobox-containing genes, Msx1, might be involved in the regulation of cell proliferation and cell cycle using Msx1 overexpressing human ovarian cancer cell line, OVCAR3. Overexpression of Msx1 in OVCAR3 cells inhibited cell proliferation by markedly increasing the length of the G1 phase of the cell cycle over control cells. Consistent with this result, dramatic suppression of cyclins D1, D3, E, cyclin-dependent kinase 4, c-Jun, and Rb was observed. Elevated expression of genes involved in the growth arrest and apoptosis (GADD153 and apoptotic cystein protease MCH4) and suppression of proliferation associated protein gene (PAG) in Msx1-overexpressing cells by cDNA expression array analysis provide further evidence for a potential repressor function of Msx1 in cell cycle progression.

Cell Division↗

Expression of the p53 homologue p63 in early cervical neoplasia.

BACKGROUND: p63, a homologue of the tumor suppressor gene p53, is expressed in embryonic, adult murine, and human basal squamous epithelium and encodes both transactivating and dominant negative transcript isoforms. Mouse embryos functionally deficient in p63 fail to replenish basal squamous epithelial cells, resulting in multiple defects that include absent genital squamous epithelium. This study investigated the expression of p63 in the human cervical transformation zone and early cervical neoplasia. METHODS: Tissue localization of p63 was determined by immunohistochemistry in a wide range of epithelia. A correlation was also made between p63 expression and squamous basal cell (keratin 14), endocervical columnar cell (mucicarmine), and cell-cycle specific (Ki-67) markers. RESULTS: p63 expression by immunostaining delineated basal and parabasal cells of maturing ectocervical squamous mucosa, squamous metaplasia in the cervix, and basal and subcolumnar cells of the cervical transformation zone. In atrophic epithelia immunostaining for p63 was present in all cell strata. In early cervical neoplasia, p63 expression was inversely correlated with both squamous cell maturation and nonsquamous differentiation in CIN. This biomarker also identified basal cells in a subset of preinvasive cervical neoplasms with endocervical cell differentiation that were bcl-2 and keratin 14 negative. CONCLUSIONS: In the lower female genital tract, p63 is preferentially expressed in immature cells of squamous lineage and is not linked to cell proliferation. The broader range of p63 expression relevant to keratin 14 and bcl-2 indicates that p63 may identify additional subsets of benign and neoplastic epithelial basal cells in the cervical transformation zone and may be useful in studying cell differentiation in the early stages of neoplastic change in this region.

Adenocarcinoma↗

Venous hemangioma of the mediastinum.

Mediastinal hemangiomas are rare tumors. We present a case of venous hemangioma of the mediastinum. Computed tomography shows anterior mediastinal solid mass without enhancement effects. We believe that it is necessary to include a mediastinal hemangioma for differential diagnosis, when little or no enhancement effects are noted at early and delayed CT examination.

Adult↗

Effectiveness of acupuncture for stroke: a systematic review.

BACKGROUND: Acupuncture has been suggested as a treatment for stroke rehabilitation, but the question whether it is effective has not been answered satisfactorily. PURPOSE: To summarise and critically review all randomised controlled trials of the effectiveness of acupuncture as a treatment for stroke. METHODS: Four independent computerised literature searches (in MEDLINE, Cochrane Controlled Trials Register, Embase, and CISCOM data bases) were conducted in June 1999. All randomised-controlled trials that compared any form of needle insertion acupuncture to any form of non-acupuncture control intervention in the treatment of human stroke patients were included. Data were extracted independently by two authors and arbitrated by a third. The methodological quality of the included studies was assessed using the Jadad score. RESULTS: Nine randomised controlled trials with a total sample size of 538 patients were included. Two studies were assessor blind, one was subject blind, and one was assessor and subject blind. Two studies exclusively used manual acupuncture, five only electroacupuncture, and two used both. Outcome measures used were Scandinavian Stroke Scale, Chinese Stroke Scale or Recovery Scale, Barthel index, Nottingham Health Profile, Motor function, balance, and days in hospital. Of the nine studies, six yielded a positive result suggesting that acupuncture is effective, and three produced a negative finding implying that acupuncture is not superior to control treatment. Only two studies obtained a Jadad score of more than 3. These methodologically best trials showed no significant effect of acupuncture. CONCLUSION: Based on the evidence of rigorous randomised controlled trials, there is no compelling evidence to show that acupuncture is effective in stroke rehabilitation. Further, better-designed studies are warranted.

Acupuncture Therapy↗

MRI phenotype is associated with response to doxorubicin and cyclophosphamide neoadjuvant chemotherapy in stage III breast cancer.

BACKGROUND: The preferred management for women with stage II or locally advanced breast cancer (LABC) is neoadjuvant chemotherapy. Pathologic response to chemotherapy has been shown to be an excellent predictor of outcome. Surrogates that can predict pathologic response and outcome will fuel future changes in management. Magnetic resonance imaging (MRI) demonstrates that patients with LABC have distinct tumor patterns. We investigated whether or not these patterns predict response to therapy. METHODS: Thirty-three women who received neoadjuvant doxorubicin and cyclophosphamide chemotherapy for 4 cycles and serial breast MRI scans before and after therapy were evaluated for this study. Response to therapy was measured by change in the longest diameter on the MRI. RESULTS: Five distinct imaging patterns were identified: circumscribed mass, nodular tissue infiltration diffuse tissue infiltration, patchy enhancement, and septal spread. The likelihood of a partial or complete response as measured by change in longest diameter was 77%, 37.5%, 20%, and 25%, respectively. CONCLUSIONS: MRI affords three-dimensional characterization of tumors and has revealed distinct patterns of tumor presentation that predict response. A multisite trial is being planned to combine imaging and genetic information in an effort to better understand and predict response and, ultimately, to tailor therapy and direct the use of novel agents.

Adult↗

Non-veridical visual motion perception immediately after saccades.

It is widely assumed that combining the eye movement vector with the motion vector of the retinal image is both sufficient and necessary for recovering the direction and speed of visual motion. Here, we report that execution of a saccadic (rapid) eye movement in the dark systematically biased subsequent perceptual judgment of the direction of visual motion in the direction opposite to the saccade. This non-veridical motion perception reached a maximum immediately after saccade offset and then decayed in approximately equal to 100 ms. These results suggest that the oculomotor signal interacts with central mechanisms related to motion and possibly form perception, as well as spatial vision, as documented with mislocalization of visual objects at the time of saccades.

Adult↗

Influence of substrate exposure history on biodegradation in a porous medium.

This study investigates the influence of fluctuating toluene concentrations on aerobic toluene degradation in a sandy porous medium colonized with Ralstonia pickettii PKO1. Column effluent toluene concentrations were found to increase after a temporary decrease in influent toluene concentration. Subsequent examination of the spatial gradient of toluene degradative activity in the column suggested that the observed increase in effluent toluene concentrations was attributable to an adverse effect of toluene limitation on the biodegradative activity of attached cells. The traditional Michaelis-Menten-type biodegradation equation associated with batch-measured Vmax (2.26 mg toluene/mg living cell/day) and KS (1.20 mg toluene/1) of nonstarved cells was unable to predict the observed toluene breakthrough behavior when the column had been previously exposed to no-toluene conditions. An alternative modeling approach was developed based upon the assumptions that (i) degradative activity was completely deactivated within the no-toluene exposure period (53.5 h) and (ii) a lag-phase was present prior to the subsequent reactivation of degradative activity in previously toluene-starved cells. These assumptions were independently verified by batch microbial investigations, and the modified model provided a good fit to the same observed toluene breakthrough curve. Application of single lag-time and threshold concentration values, however, failed to predict observed toluene breakthrough under different toluene exposure conditions. Results of this experimental and modeling investigation suggested that substrate exposure history, including the length of the starvation period and the level of substrate concentration, affected the induction of biodegradation in the porous medium.

Biodegradation, Environmental↗

Infant care practices in New Zealand: a cross-cultural qualitative study.

This paper describes and compares the infant care practices and beliefs of Maori, Tongan, Samoan, Cook Islands, Niuean and Pakeha (European) caregivers residing in Auckland, New Zealand. Focusing on four areas--sources of support and advice; infant feeding; infant sleeping arrangements; and traditional practices and beliefs--it explores inter-ethnic similarities and differences and intra-ethnic tensions. The international literature indicates that there can be significant cultural variation in infant care practices and in the meanings attributed to them. There is, however, little New Zealand literature on this topic, despite its importance for effective health service and health message delivery. Participants were primary caregivers of infants under 12 months. An average of six focus groups were conducted within each ethnic group, resulting in a total of 37 groups comprising 150 participants. We found similarities across all ethnic groups in the perceived importance of breastfeeding and the difficulties experienced in establishing and maintaining this practice. The spectrum of behaviours ranged widely with differences most pronounced between Pacific caregivers, especially those Island-raised, and Pakeha caregivers, especially those in nuclear families. Amongst the former, norms included: the family as central in providing support and advice; infant bedsharing; abdominal rubbing during pregnancy; baby massage; and the importance of adhering to traditional protocols to ensure infant well-being. Amongst the latter, norms included: strong reliance on professional advice; looser family support networks; the infant sleeping in a cot; and adherence to Western biomedical understandings of health and illness. Maori caregivers bridged the spectrum created by these groups and exhibited a diverse range of practices. Intra-cultural differences were present in all groups indicating the dynamic nature of cultural practices. They were most evident between Pacific-raised and New Zealand-raised Pacific caregivers, with the latter attempting to marry traditional with Western beliefs and practices.

Humans↗

Cytoprotective effect of Scutellaria baicalensis in CA1 hippocampal neurons of rats after global cerebral ischemia.

Based on the use of Scutellaria baicalensis for the treatment of stroke in traditional Oriental medicine, the current study was carried out to evaluate neuroprotective effects of S. baicalensis after transient global ischemia using rat 4-vessel occlusion model. Methanol extracts from the dried roots of S. baicalensis (0.1-10 mg/kg) administered intra-peritoneally significantly protected CA1 neurons against 10 min transient forebrain ischemia as demonstrated by measuring the density of neuronal cells stained with Cresyl violet. Methanol extract of S. baicalensis inhibited microglial tumor necrosis factor-alpha (TNF-alpha) and nitric oxide production, and protected PC12 cells from hydrogen peroxide-induced toxicity in vitro.

Animals↗

A synthesis procedure for associative memories based on space-varying cellular neural networks.

In this paper, we consider the problem of realizing associative memories via space-varying CNNs (cellular neural networks). Based on some known results and a newly derived theorem for the CNN model, we propose a synthesis procedure for obtaining a space-varying CNN that can store given bipolar vectors with certain desirable properties. The major part of our synthesis procedure consists of solving generalized eigenvalue problems and/or linear matrix inequality problems, which can be efficiently solved by recently developed interior point methods. The validity of the proposed approach is illustrated by a design example.

Memory↗

A sequential neural network model for diabetes prediction.

This paper presents a neural network (NN) model to evaluate an existing Health Risk Appraisal (HRA) for diabetes prediction over 3 years (1996-1998) based on a simulated learning algorithm on individual prognostic process, using the repeatedly measured HRAs of 6142 participants. The approach uses a sequential multi-layered perceptron (SMLP) with backpropagation learning, and an explicit model of time-varying inputs along with the sequentially obtained prediction probability, which was obtained by embedding a multivariate logistic function for consecutive years. The study captures the time-sensitive feature of associating risk factors as predictors to the occurrence of diabetes in the corresponding period. This approach outperforms the baseline classification and regression models in terms of gains (average profit: 0.18) and sensitivity (86.04%) for a test data. The result enables a time-sensitive disease prevention and management program as a prospective effort.

Diabetes Mellitus↗

Improvement of the physical properties of reprocessed paper by using biological treatment with modified cellulase.

A primary need for waste paper reprocessing is to preserve optical properties and the physical strength of the paper fibers. In this study, modified cellulase with copolymer, polyethylene oxide (PEO) derivatives and maleic anhydride (MA) was applied to the reprocessing of mixed office waste (MOW). Modified cellulase was prepared by a chemical reaction between amino groups of the cellulase and the MA functional groups of the copolymer. In MOW reprocessing, modified cellulase improved several physical properties of the paper including freeness, optical properties, and physical strength compared to the conventional process. Even though native cellulase improved the physical properties, paper treated with modified cellulase exhibited an increase in physical properties such as tensile strength and internal bond over those of unmodified cellulase. From these results, modified cellulase method is a new biological treatment that will save pulp resources, which are added to waste paper reprocessing to maintain the strength of paper.

Cellulase↗

Laparoscopic myomectomy after failure of uterine artery embolization.

A patient experienced continuing pain and growth of a broad-based pedunculated myoma 6 months after uterine artery embolization (UAE). A 7-cm myoma was found growing directly from the serosa of the fallopian tube and was removed laparoscopically. To our knowledge, this is the first report of laparoscopic myomectomy performed after failure of UAE. This case identifies one of the predictable limitations of UAE of which gynecologists must be cognizant when recommending the procedure.

Embolization, Therapeutic↗