Biomedical subjects

S Park

Publications and source records attributed to S Park.

At least 109 records · Page 6Linked to original sources

PubMed2001

Postmenopausal obesity as a breast cancer risk factor according to estrogen and progesterone receptor status (Japan).

There have been inconsistent results on the association of postmenopausal obesity with breast cancer risk according to the estrogen (ER) and/or progesterone receptor (PR) status in the breast tissue, and this requires further evaluation. This study was designed to assess whether postmenopausal obesity differs according to receptor status. Information on risk factors was obtained from 1154 breast cancer cases and 21714 controls at Aichi Cancer Center Hospital, Nagoya, Japan between 1988 and 1992. The receptor status was known for 40% of cases. Obese postmenopausal women showed an increased risk of breast cancer (odds ratio (OR) for 5 kg of current weight=1.17, 95% confidence interval (CI)=1.10-1.25; OR for 1 kg/m(2) of body mass index (BMI)=1.07, 95% CI=1.04-1.10). The elevated OR was strongest for ER-positive, as well as with PR-positive, breast cancer among postmenopausal women who had a high BMI. The risk did not differ significantly according to ER status. However, obesity indices among postmenopausal women differed with borderline significance according to PR status. These results are consistent with the hypothesis that there is a gradient of risk for postmenopausal obesity according to hormonal receptor status, at least for PR status, although this was not statistically significant.

Adult↗

PubMed2001

Conformation of myosin interdomain interactions during contraction: deductions from muscle fibers using polarized fluorescence.

Myosin cross-bridge subfragment 1 (S1) is the ATP catalyzing motor protein in muscle. It consists of three domains that catalyze ATP and bind actin (catalytic), conduct energy transduction (converter), and transport the load (lever arm). Force development during contraction is thought to result from rotary lever arm movement with the cross-bridge attached to actin. To elucidate cross-bridge structure during force development, two crystal structures of S1 were extrapolated to working "in solution" or oriented "in tissue" forms, using structure-sensitive optical spectroscopic signals from two extrinsic probes. The probes were located at two interfaces containing the catalytic, converter, and lever arm domains of S1. Observed signals included circular dichroism (CD) and absorption originating from S1 in solution in the presence and absence of actin and fluorescence polarization from cross-bridges in muscle fibers. Theoretical signals were calculated from S1 crystal structure models perturbed with lever arm movement from swiveling at three conserved glycines, 699, 703, and 710 (chicken skeletal myosin numbering). Best agreement between the computed and observed signals gave structures showing that actin binding to S1 causes movement of the lever arm. A three-state model of S1 conformation during contraction consists of three actin-bound cross-bridge states observed from muscle fibers in isometric contraction, in the presence of MgADP, and in rigor. Structures best representing these states show that most of the lever arm rotation occurs between isometric contraction and the MgADP states, i.e., during phosphate release. Smaller but significant lever arm rotation occurs with ADP dissociation. Structural changes within the S1 interfaces studied are discussed in the accompanying paper [Burghardt et al. (2001) Biochemistry 40, 4834-4843].

Animals↗

PubMed2001

Conformation of myosin interdomain interactions during contraction: deductions from proteins in solution.

Myosin subfragment 1 (S1) is the ATP catalyzing motor protein in muscle. It consists of three domains that catalyze ATP and bind actin (catalytic), conduct energy transduction (converter), and transport the load (lever arm). These domains interface in two places identified as interface I, containing the reactive thiol (SH1) and ATP-sensitive tryptophan (Trp510), and interface II, containing the reactive lysine residue (RLR). Two crystal structures of S1 were extrapolated to working "in solution" or oriented "in tissue" forms, using structure-sensitive optical spectroscopic signals from extrinsic probes located in the interfaces. Observed signals included circular dichroism (CD) and absorption originating from S1 in solution in the presence and absence of actin and fluorescence polarization from cross-bridges in muscle fibers. Theoretical signals were calculated from S1 crystal structure models perturbed with lever arm movement from swiveling at three conserved glycines, 699, 703, and 710 (chicken skeletal myosin numbering). Structures giving the best agreement between the computed and observed signals were selected as the representative forms. Both interfaces undergo dramatic conformational change during ATPase and force development. Changes at interface I suggest the molecular basis for the collisional quenching sensitivity of Trp510 to nucleotide binding. The probe conformation at SH1 suggests how it alters S1 ATPases. At interface II, the spatial relationship of the lever arm and the extrinsic probe at RLR suggests how the probe alters S1 ATPases and that it should inhibit lever arm movement during the power stroke. The latter possibility, if true, establishes a part of the corridor through which the lever arm swings during the power stroke. Global structural changes in actomyosin are discussed in the accompanying paper [Burghardt et al. (2001) Biochemistry 40, 4821-4833].

Actins↗

PubMed2001

Selection of the recipient vessel in the free flap around the knee: the superior medial genicular vessels and the descending genicular vessels.

In reconstructions around the knee, the use of a free flap is indicated in a limited number of cases, but it plays a critical role in cases of extensive defects or unavailability of local flaps. The selection of the recipient vessel is an essential and challenging step for a successful free tissue transfer. Popliteal vessels and other small vessels around the knee have been reported to be used as recipient vessels, but the choice of recipient vessels around the knee has not been established. In this study, after a thorough investigation of the vascular anatomy at the knee region, the superior medial genicular vessels and the descending genicular vessels were considered to be the proper recipient vessels, and a clinical application was tried. From July of 1997 to July of 1999, a total of seven cases of soft-tissue defects around the knee-four cases in the posterior region and three cases in the anterior region-were reconstructed with free flaps, using the superior medial genicular vessels and the descending genicular vessels, respectively. All flaps survived completely, with no flap loss. The advantages of these vessels are their proximity to the knee and their reliability, versatility, simplicity, and size match. The outstanding characteristic of this combination of vessels is their versatility, because the combination can cover all defects around the knee. The clinical application and the versatility of the combination of the superior medial genicular vessels and the descending genicular vessels as the recipient vessels was confirmed for the reconstruction of posterior and anterior knee defects.

Adolescent↗

PubMed2001

The alterations of N-Methyl-D-aspartate receptor expressions and oxidative DNA damage in the CA1 area at the early time after ischemia-reperfusion insult.

Delayed neuronal death in the CA1 of the hippocampus following global ischemia has been evoked by both the activation of N-methyl-D-aspartate receptor (NR) and the generate reactive oxygen species in the neurons. In the present study, we investigated whether oxidative DNA damages may be correlated with NR subunits (NR1 and NR2A/B) expression following ischemia insults in vivo. Thirty minutes after ischemia-reperfusion, the intensities of both NR and 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunoreactivities were markedly increased in neurons of CA1. However, NR2A/B and 8-OHdG immunoreactivities were enhanced in CA1 over 24 h after ischemia although NR1 immunoreactivity was decreased. These results suggest that oxidative stress and excitotoxicity in the CA1 may simultaneously trigger neuronal damages at early time after ischemia, and free radical damage including oxidative DNA damage may eventually promote the delayed neuronal death in this region.

Animals↗

PubMed2001

Oligomerization-dependent regulation of motility and morphogenesis by the collagen XVIII NC1/endostatin domain.

Collagen XVIII (c18) is a triple helical endothelial/epithelial basement membrane protein whose noncollagenous (NC)1 region trimerizes a COOH-terminal endostatin (ES) domain conserved in vertebrates, Caenorhabditis elegans and Drosophila. Here, the c18 NC1 domain functioned as a motility-inducing factor regulating the extracellular matrix (ECM)-dependent morphogenesis of endothelial and other cell types. This motogenic activity required ES domain oligomerization, was dependent on rac, cdc42, and mitogen-activated protein kinase, and exhibited functional distinction from the archetypal motogenic scatter factors hepatocyte growth factor and macrophage stimulatory protein. The motility-inducing and mitogen-activated protein kinase-stimulating activities of c18 NC1 were blocked by its physiologic cleavage product ES monomer, consistent with a proteolysis-dependent negative feedback mechanism. These data indicate that the collagen XVIII NC1 region encodes a motogen strictly requiring ES domain oligomerization and suggest a previously unsuspected mechanism for ECM regulation of motility and morphogenesis.

Angiogenesis Inhibitors↗

PubMed2001

Candida dubliniensis at a cancer center.

Candida dubliniensis, a germ tube-positive yeast first described and identified as a cause of oral candidiasis in patients with acquired immunodeficiency syndrome in Europe in 1995, has an expanding clinical and geographic distribution that appears to be similar to that of the other germ tube-positive yeast, Candida albicans. This study determined the frequency, clinical spectrum, drug susceptibility profile, and suitable methods for identification of this emerging pathogen at a cancer center in 1998 and 1999. Twenty-two isolates were recovered from 16 patients with solid-organ or hematologic malignancies or acquired immunodeficiency syndrome. Two patients with cancer had invasive infection, and 14 were colonized with fungus or had superficial fungal infection. All isolates produced germ tubes and chlamydospores at 37 degrees C, did not grow at 45 degrees C, and gave negative reactions with d-xylose and alpha-methyl-d-glucoside in the API 20 C AUX and ID 32 C yeast identification systems. Phenotypic identification was confirmed by molecular beacon probe technology. All isolates were susceptible to the antifungal drugs amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, and ketoconazole.

Adult↗

PubMed2001

Cannabis use is associated with schizotypy and attentional disinhibition.

While most neurochemical research into the pathogenesis of schizophrenia (SZ) has focused on the dopaminergic, glutamatergic, and serotonergic systems, the exact nature and cause of this disorder have proven intractable. Given the recent discovery and elucidation of the endogenous cannabinioid system, a re-examination of the cannabis-induced exacerbation hypothesis of SZ is warranted. The purpose of the present study was to assess whether current cannabis users exhibit personality correlates and neurocognitive deficits similar to those observed in SZ patients. 15 current cannabis users, 15 drug-free controls, and 10 past cannabis users were assessed on tasks which assess attentional inhibition, spatial working memory, olfactory identification, and schizotypal personality. Current cannabis users demonstrated deficits in attentional inhibition, decreased reaction time, and significantly higher scores on the schizotypal personality questionnaire (SPQ) compared with the non-using and past cannabis using groups. No group differences were found on the working memory or olfactory identification tasks. These results suggest that cannabis use can mimic attentional deficits seen in acute schizophrenia and is associated with schizotypal personality, thus setting the stage for a possible cannabinoid model of SZ.

Adult↗

PubMed2001

A single gene (yes) controls pigmentation of eyes and scales in Heliothis virescens.

A yellow-eyed mutant was discovered in a strain of Heliothis virescens, the tobacco budworm, that already exhibited a mutation for yellow scale, y. We investigated the inheritance of these visible mutations as candidate markers for transgenesis. Yellow eye was controlled by a single, recessive, autosomal factor, the same type of inheritance previously known for y. Presence of the recombinant mutants with yellow scales and wild type eyes in test crosses indicated independent segregation of genes for these traits. The recombinant class with wild type scales and yellow eyes was completely absent and there was a corresponding increase of the double mutant parental class having yellow scales and yellow eyes. These results indicated that a single factor for yellow eye also controlled yellow scales independently of y. This gene was named yes, for yellow eye and scale. We hypothesize that yes controls both eye and scale color through a deficiency in transport of pigment precursors in both the ommochrome and melanin pathways. The unlinked gene y likely controls an enzyme affecting the melanin pathway only. Both y and yes segregated independently of AceIn, acetylcholinesterase insensitivity, and sodium channel hscp, which are genes related to insecticide resistance.

Acetylcholinesterase↗

PubMed2001

Reduction in cyclin D1/Cdk4/retinoblastoma protein signaling by CRE-decoy oligonucleotide.

We have previously demonstrated that the activation of p53 signaling may contribute to tumor growth inhibition by the CRE-decoy oligonucleotide containing CRE sequence (5'-TGACGTCA-3') (Lee et al., Biochemistry 39, 4863-4868, 2000). However, growth inhibition by CRE-decoy treatment was also observed in tumor cells containing a mutant p53 (Park et al., J. Biol. Chem. 274, 1573-1580, 1999). To understand additional mechanisms of the decoy oligonucleotide, we investigated the effect on cyclin D1 expression and a cyclin D1/Cdk4/retinoblastoma protein (pRB) signaling pathway. Here we show that in MCF7 breast cancer cells the CRE-decoy competed with cyclin D1-CRE (5'-TAACGTCA-3') for binding transcription factors and reduced cyclin D1 gene expression (in reporter gene assay, Northern blotting and Western blotting) to modulate cyclin D1/Cdk4/pRB signaling and G1-S progression in a steady state and/or under estrogen stimulation. Decrease of cyclin D1 protein level by CRE-decoy treatment was also observed in p53-mutated cancer cells. Cyclin D1 expression was also diminished in MCF7 cells stably expressing dominant negative mutant CREB indicating that the nonspecific effect of oligonucleotide or its degradation products could be excluded. These data suggest that inhibition of cyclin D1 expression contributes to the growth inhibition induced by the decoy oligonucleotide in MCF7 cells through a cyclin D1/Cdk4/pRB signaling pathway. Downregulation of cyclin D1 expression also provides a mechanism of CRE-decoy-induced growth inhibition in tumor cells having p53 mutation.

Breast Neoplasms↗

PubMed2001

Sharpin, a novel postsynaptic density protein that directly interacts with the shank family of proteins.

The Shank family of proteins (also termed CortBP, ProSAP, or Synamon) is highly enriched in the postsynaptic density (PSD) of excitatory synapses in brain. Shank contains multiple domains for protein-protein interactions, including ankyrin repeats, SH3 domain, PDZ domain, SAM domain, and an extensive proline-rich region. We have identified a novel protein, termed Sharpin, that directly interacts with the ankyrin repeats of Shank. Sharpin is enriched in the PSD and forms a complex with Shank in heterologous cells and brain. Immunostaining reveals the presence of Sharpin at excitatory synapses and its colocalization with Shank. While the C-terminal half of Sharpin interacts with Shank, the N-terminal half of Sharpin mediates homomultimerization. Considering the fact that the ankyrin repeats and the SH3 domain of Shank can be truncated by alternative splicing, these results define Sharpin as a novel PSD protein that may regulate the complexity of the Shank-based protein network in an alternative splicing-dependent manner.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Immunobead RT-PCR versus regular RT-PCR amplification of CEA mRNA in peripheral blood.

PURPOSE: The reverse transcription polymerase chain reaction (RT-PCR) amplification of tumor-specific mRNA has been used for the detection of cancer cells in peripheral blood. More recently, an immunomagnetic isolation and reverse transcription polymerase chain reaction (immunobead RT-PCR) was developed which has reportedly significant advantages over the previous RT-PCR analysis. In our study, we compared these two methods using a model set of peripheral blood containing tumor cells under standardized conditions. MATERIAL AND METHODS: In order to compare the false positive rate, normal peripheral blood samples from five volunteers were analyzed by both methods. A model set of peripheral blood containing tumor cells was established by adding SNUC4 human colon cancer cells to peripheral blood collected from normal volunteers not showing any nonspecific bands upon electrophoresis of the PCR products. RT-PCR amplification of carcinoembryonic antigen (CEA) mRNA was done with total RNA and mRNA prepared from this model sample. In immunobead RT-PCR analysis, mRNA was prepared from the cells isolated with anti-CEA antibody-coated magnetic beads or anti-Ber-EP4 antibody-coated magnetic beads before the RT-PCR analysis. RESULT: The immunobead RT-PCR yielded no non-specific band, while the regular RT-PCR using total RNA did show non-specific band formation in all five samples. When mRNA rather than total RNA was used, nonspecific bands were formed in three of the five samples. Immunobead RT-PCR allowed the detection of 10(1) tumor cells in 1 ml of peripheral blood. The regular RT-PCR analysis had a detection limit of 10(2) tumor cells in 1 ml of peripheral blood. CONCLUSION: The immunobead RT-PCR proved to be more sensitive and specific than the regular RT-PCR at least in our model system.

Antibodies, Monoclonal↗

PubMed2001

Experimental autoimmune myocarditis in A/J mice is an interleukin-4-dependent disease with a Th2 phenotype.

Myocarditis in humans is often associated with an autoimmune process in which cardiac myosin (CM) is a major autoantigen. Experimental autoimmune myocarditis (EAM) is induced in mice by immunization with CM. We found that EAM in A/J mice exhibits a Th2-like phenotype demonstrated by the histological picture of the heart lesions (eosinophils and giant cells) and by the humoral response (association of IgG1 response with disease and up-regulation of total IgE). Blocking interleukin (IL)-4 with anti-IL-4 monoclonal antibody (mAb) reduced the severity of EAM. This reduction in severity was associated with a shift from a Th2-like to a Th1-like phenotype represented by a reduction in CM-specific IgG1; an increase in CM-specific IgG2a; an abrogation of total IgE response; a decrease in IL-4, IL-5, and IL-13; as well as a dramatic increase in interferon (IFN)-gamma production in vitro. Based on the latter finding, we hypothesized that IFN-gamma limits disease. Indeed, IFN-gamma blockade with a mAb exacerbated disease. The ameliorating effect of IL-4 blockade was abrogated by co-administration of anti-IFN-gamma mAb. Thus, EAM represents a model of an organ-specific autoimmune disease associated with a Th2 phenotype, in which IL-4 promotes the disease and IFN-gamma limits it. Suppression of IFN-gamma represents at least one of the mechanisms by which IL-4 promotes EAM.

Animals↗

PubMed2001

Expression of leukemia-associated antigen, JL1, in bone marrow and thymus.

The identification of immunophenotypic markers with restricted expression has long been a critical issue in diagnostic and therapeutic advances for acute leukemias. We previously developed a monoclonal antibody against a new thymocyte surface antigen, JL1, and showed that JL1 is expressed in the majority of acute leukemia cases. In this study, using multiparameter flow cytometric analyses, we found that JL1 was uniquely expressed in subpopulations of normal bone marrow (BM) cells, implying the association of JL1 with the differentiation and maturation process. Although CD34(+) CD10(+) lymphoid precursors and some of maturing myeloid cells express JL1, neither CD34(+) CD38(-/lo) nor CD34(+) AC133(+) noncommitted pluripotent stem cells do. As for the myeloid precursors, CD34(+) CD33(+) cells do not express JL1. During lymphopoiesis, JL1 on the earliest lymphoid precursors disappear in the CD20(+) sIgM(+) stage of B-cell development or after CD1a down-regulation in thymocytes. Despite the highly restricted expression of JL1 in normal BM cells, most of the leukemias express JL1 irrespective of their immunophenotypes. These results indicate that JL1 is not only a novel differentiation antigen of hematopoietic cells, but also a leukemia-associated antigen. Therefore, we suggest that JL1 be a candidate molecule in acute leukemia for the diagnosis and immunotherapy that spares the normal BM stem cells.

Adult↗

PubMed2001

Extramammary Paget's disease of the penis and scrotum: excision, reconstruction and evaluation of occult malignancy.

PURPOSE: We describe treatment and reconstruction in patients after surgery for extramammary Paget's disease of the penis and scrotum. We also investigated whether this disease causes an increased risk of undiagnosed visceral malignancy. MATERIALS AND METHODS: We reviewed the databases at our institution from 1996 to 2000 and identified 6 men 67 to 87 years old (mean age 76). In addition, we reviewed the literature on the clinical and pathological features of this disease. RESULTS: In our 6 patients scrotal involvement was present in 83% and penile extramammary Paget's disease was present in 33%. Each man underwent wide local excision and large skin defects were immediately reconstructed with split-thickness skin grafts. In 1 case extramammary Paget's disease had spread to the superficial inguinal nodes. At a mean followup of 29 months there has been no local recurrence and internal malignancy has not been diagnosed. Our literature review revealed 13 patients with penoscrotal extramammary Paget's disease and visceral malignancy, including 12 (92%) with malignancy of the genitourinary system. CONCLUSIONS: Extramammary Paget's disease of the penis and scrotum is a rare disease that can be managed by excision and immediate reconstruction with skin grafting or a local skin flap. Disease may spread to the regional lymph nodes. Although genitourinary cancer may accompany penoscrotal extramammary Paget's disease, an extensive search for cancer of the thorax or abdomen may be unnecessary because only 1 reported case of colon cancer has been associated with penile or scrotal extramammary Paget's disease.

Aged↗

PubMed2001

Allogeneic bone marrow transplantation for chronic myeloid leukemia: a retrospective study of busulfan-cytoxan versus total body irradiation-cytoxan as preparative regimen in Koreans.

From January 1990 to December 1997, 53 Korean patients with chronic myeloid leukemia (CML) receiving bone marrow transplantation (BMT) from human leucocyte antigen (HLA)-identical sibling donors conditioned with either busulfan and cyclophosphamide (BU/CY regimen) or total body irradiation and cyclophosphamide (TBI/CY regimen) were compared retrospectively. Transplantation-related mortality was 19% in BU/CY and 12% in TBI/CY, and early death (<100 d) occurred in 3 patients conditioned with BU/CY. Grade II-IV acute graft-versus-host disease (GVHD) was 9% of BU/CY and 52% of TBI/CY patients. Overall incidence of chronic GVHD was 50% of BU/CY and 52% of TBI/CY patients. In patients with chronic phase, 5-yr overall survival was 73% in the BU/CY group compared with 87% in the TBI/CY group (p=NS), and overall disease-free survival was 75% in the BU/CY group and 59% in the TBI/CY group (p=NS). So far, with a median follow-up of 45 months, 11 patients have relapsed; three relapses occurred after BU/CY and 8 after TBI/CY. The actuarial 5-yr relapse rate was 15% after BU/CY, 34% after TBI/CY (p=0.46). For patients transplanted in chronic phase within 1 yr after diagnosis, there was a clear trend for a lower relapse rate in the BU/CY group (5-yr relapse rate 0%) compared with the TBI/CY group (5-yr relapse rate 30%). The BU/CY group had similar BMT-related toxicity and similar overall survival and showed a clear trend of low relapse compared with the TBI/CY group. Therefore, BU/CY is an acceptable alternative for patients with CML during HLA-identical sibling allogeneic BMT.

Adult↗

PubMed2001

Analysis of steroid-induced genes in the rat preoptic area-anterior hypothalamus using a differential-display reverse transcriptase-polymerase chain reaction.

Steroid hormones modulate a variety of physiological functions in the hypothalamus. We attempted to identify steroid-regulated genes in the rat preoptic area-anterior hypothalamus by comparing differentially expressed mRNAs. Adult female rats were ovariectomized and, 1 week later, a silastic capsule containing 17beta-oestradiol (180 microg/ml) was subcutaneously implanted. After 2 days, a single injection of progesterone (1 mg) was administered at 10.00 h and rats were killed at 17.00 h on the same day. Differential-display polymerase chain reaction followed by Northern blot analysis showed that 10 clones were differentially regulated. Using homology search in Genbank, three genes were identified as sodium, potassium-ATPase beta1, protein kinase C-binding Nell-homologue protein and evectin-1. Further characterization of 10 clones showed that the expression patterns were tissue-specific and differentially regulated during puberty. Among these, mRNAs for protein kinase C-binding Nell-homologue protein, evectin-1 and human CGI-118 protein-like gene were induced after vagina opening, and differentially expressed during the oestrous cycle. Taken together, several steroid-regulated genes identified in the present study may play an important role in regulating hypothalamic functions, including puberty and the oestrous cycle.

Animals↗

PubMed2001

Determination of binding constant of transcription factor AP-1 and DNA. Application of inhibitors.

The equilibrium binding and association kinetics of the fos-jun dimer (basic and leucine zipper domain) to the AP-1 DNA were studied using a quantitative assay. The basic-region and leucine zipper (bZip) domain of c-fos was expressed as a fusion protein with glutathione S-transferase, and it was bound to glutathione-agarose. The GST-fused fos bZip region was allowed to form a heterodimer with the bZip domain of c-jun, to which radiolabeled AP-1 nucleotides were added. After thorough washing, the gel-bound radioactivity was counted. The binding and dissociation rate constants (k(1) and k-(1)) of the fos-jun dimer and DNA could be obtained from a time-course experiment. The association binding constant (K(1)) was determined using both a thermodynamic equation and kinetic parameters. Nordihydroguaiaretic acid (NDGA), momordin I, natural product inhibitors of the fos-jun/DNA complex formation, was applied to this jun-GST-fused fos system and it was found to decrease the apparent equilibrium binding of dimer and DNA. The thermodynamic constant of dimer and inhibitor binding was also determined.

Cloning, Molecular↗