Biomedical subjects
Publications and source records attributed to J Park.
SUMMARY: DaliLite is a program for pairwise structure comparison and for structure database searching. It is a standalone version of the search engine of the popular Dali server. A web interface is provided to view the results, multiple alignments and 3D superimpositions of structures.
Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus that is implicated in the pathogenesis of Kaposi's sarcoma. The nucleotide sequence of the KSHV open reading frame (ORF) 36 predicts a polypeptide with significant sequence homology to known protein kinases. In this paper, we show that KSHV ORF36 mRNA is expressed during lytic growth and that ORF36 protein is localized in the nucleus. To determine whether the KSHV ORF36 protein is a protein kinase, we expressed it as a glutathione S-transferase (GST) fusion protein (GST-ORF36). Affinity-purified preparations of the GST-ORF36 fusion protein revealed that the protein is autophosphorylated. Mutation of lysine-108 to glutamine dramatically decreased the protein kinase activity of the purified protein, supporting the hypothesis that the protein kinase activity is inherent to the ORF36 protein. Phosphoamino acid analysis showed that the KSHV ORF36 fusion protein is phosphorylated on a serine residue, implying that KSHV ORF36 encodes a serine protein kinase.
Plant cells produce reactive oxygen species (ROS) in response to many stimuli. However, the mechanism of ROS biosynthesis remains unclear. We have explored the hypothesis that the superoxide burst in plants mechanistically resembles the oxidative burst in neutrophils. First we have confirmed that ROS production, which occurs in suspension-cultured soybean (Glycine max) cells in response to hypo-osmotic shock, is inhibited by diphenylene iodonium, an inhibitor of the flavin-dependent oxidase of neutrophils. Because a Rac family G protein is an essential regulator of this NADPH oxidase, and because many plant homologs of Rac have been cloned, we next examined whether Rac-like proteins might be involved in the oxidative burst in the soybean cells. We identified a Rac-like 21-kD soybean protein that cross-reacts with antibodies to human Rac and garden pea Rop and also binds [gamma-(35)S] GTP, a diagnostic trait of small G proteins. This Rac-related protein translocated from the cytosol to microsomes during the oxidative burst. Moreover, soybean cells transiently transformed with either a dominant negative (RacN17) or a dominant positive (RacV12) form of Rac1 showed the anticipated altered responses to three different stimuli: hypo-osmotic shock, oligo-GalUA, and harpin. In response to these stimuli, cells transformed with RacN17 produced less ROS and cells transformed with RacV12 generated more ROS than control cells. These results strongly suggest that a Rac-related protein participates in the regulation of ROS production in soybean cells, possibly via activation of an enzyme complex similar to the NADPH oxidase of phagocytes in animal systems.
Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus that has been implicated in the pathogenesis of Kaposi's sarcoma. KSHV encodes K-bZIP (open reading frame K8), a protein that belongs to the basic region-leucine zipper (bZIP) family of transcription factors. Here we show that K-bZIP associates with the cellular transcription factor p53 directly in vitro and in vivo. This interaction requires the bZIP domain of K-bZIP and the carboxy-terminal region (amino acids 300 to 393) of p53. We also show that K-bZIP represses the transcriptional activity of p53 which is required for apoptosis of the host cell. These results imply that K-bZIP blocks p53-mediated host cell death through its interaction with p53.
Human fibroblast activation protein (FAP), a member of the serine prolyl oligopeptidase family, is a type II cell surface glycoprotein selectively expressed by fibroblastic cells in areas of active tissue remodeling, such as the embryonic mesenchyme, areas of wound healing, the gravid uterus, and the reactive stroma of epithelial cancers. Homologues of FAP have been identified in the mouse and Xenopus laevis. FAP is a dual-specificity enzyme that acts as a dipeptidyl peptidase and collagenase in vitro. To explore the role of FAP in vivo, Fap(-/-) mice were generated by homologous recombination. RNase protection analysis and reverse transcription-PCR confirmed the absence of full-length Fap transcripts in mouse embryonic tissues. No FAP protein was detected in Fap(-/-) animals by immunohistochemistry, and no FAP-specific dipeptidyl peptidase activity was found. We report that Fap(-/-) mice are fertile, show no overt developmental defects, and have no general change in cancer susceptibility.
This article is concerned with the synthesis of the optimally performing GBSB (generalized brain-state-in-a-box) neural associative memory given a set of desired binary patterns to be stored as asymptotically stable equilibrium points. Based on some known qualitative properties and newly observed fundamental properties of the GBSB model, the synthesis problem is formulated as a constrained optimization problem. Next, we convert this problem into a quasi-convex optimization problem called GEVP (generalized eigenvalue problem). This conversion is particularly useful in practice, because GEVPs can be efficiently solved by recently developed interior point methods. Design examples are given to illustrate the proposed approach and to compare with existing synthesis methods.
The purpose of this study was to develop a cost-effective protocol for the mobilization of peripheral blood stem cells (PBSC) in patients with malignancy. Thirty consecutive patients were randomized to mobilize PBSC with the late addition of a standard 250 microg dose of G-CSF (Neutrogen) from day 8 or early addition of the same dose of G-CSF from day 2, following cyclophosphamide (CY) 4 g/m2. The median yield of CD34+ cells from evaluated patients was 7.87 x 10(6)/kg (range, 2.06-27.25), collected in a median of four apheresis (range, 2-9). Target CD34 + cell doses > or = 2.0 x 10(6)/kg were achieved in all patients able to be evaluated. There were no statistically significant differences in CD34+ cell yields or toxicities. Overall engraftment occurred with median days to neutrophils > or = 0.5 x 10(9)/L or platelets > 20 x 10(9)/L of 11 and 17 days, respectively. However, the duration of G-CSF administration was markedly shorter in the late use of G-CSF group than in the early use of G-CSF group, with a median of 9 days compared with 15 days (p<0.001). PBSC harvesting after priming with CY plus delayed use of G-CSF made it a safe and cost-effective procedure.
We attempted to assess the accuracy of the International Classification of Diseases (ICD) codes for myocardial infarction (MI) in medical insurance claims, and to investigate the reasons for any inaccuracy. This study was designed as a preliminary study to establish a surveillance system for cardiovascular diseases in Korea. A sample of 258 male patients who were diagnosed with MI from 1993 to 1997 was selected from the Korea Medical Insurance Corporation cohort (KMIC cohort: 183,461 people). The registered medical record administrators were trained in the survey technique, and gathered data by investigating the medical records of the study subjects from March 1999 to May 1999. The definition of MI for this study included symptoms pursuant to the diagnostic criteria of chest pain, electrocardiogram (ECG) findings, cardiac enzyme and results of coronary angiography or nuclear scan. We asked the record administrators for the reasons of incorrectness for cases where the final diagnosis was 'not MI'. The accuracy rate of the ICD codes for MI in medical insurance claims was 76.0% (196 cases) of the study sample, and 3.9% (ten cases) of the medical records were not available due to hospital closures, non-computerization or missing information. Nineteen cases (7.4%) were classified as insufficient due to insufficient records of chest pain, ECG findings, or cardiac enzymes. The major reason of inaccuracy in the disease code for MI in medical insurance claims was 'to meet the review criteria of medical insurance benefits (45.5%)'. The department responsible for the inaccuracy was the department of inspection for medical insurance benefit of the hospitals.
We have shown that neonatal lymphocytes are deficient in TNF-induced apoptosis. Recently, a 60 kDa protein termed silencer of death domains (SODD) has been shown to prevent spontaneous apoptosis. The binding of SODD to DD of the TNFR-I maintains DD in monomeric form and prevents their aggregation which is required for the apoptotic signal. We examined the expression of SODD mRNA during TNF-induced apoptosis. Although in non-stimulated cord blood lymphocytes the constitutive expression of SODD mRNA was lower than that of non-stimulated peripheral blood lymphocytes, following anti-CD3 stimulation SODD mRNA was significantly increased in cord blood lymphocytes at 12 and 24 h, returning to the baseline at 48 h. In contrast, a modest decrease in SODD transcript was observed in peripheral blood lymphocytes. Furthermore, TNF downregulated SODD mRNA expression in peripheral blood lymphocytes, whereas it had no significant effect on SODD transcripts in cord blood lymphocytes. Therefore, differential regulation of SODD may be one of the mechanisms responsible for decreased TNF-induced apoptosis in neonatal lymphocytes.
OBJECTIVES: Gastric resection may predispose gallstone formation. However, the mechanism has not been clearly understood. To evaluate the relationship between gastric resection and gallstone formation, we compared gallbladder(GB) motility in gastrectomized patients and control subjects. METHODS: We compared the GB volume and ejection fraction of the 46 gastrectomized patients with 37 healthy controls using real time ultrasonography. RESULTS: GB volume increased significantly in the gastrectomized group in fasting (30.2 +/- 13.9 ml). The GB volume after a fatty meal was greater in the gastrectomized group (12.6 +/- 6.4 ml) than in the control group (4.3 +/- 3.3 ml) (p < 0.01). A significant reduction of ejection fraction was found in gastrectomized patients (56.9 +/- 13.0%) in comparison with the control group (75.5 +/- 16.1%) (p < 0.01). The GB ejection fraction had a poor correlation to the postoperative period (r = 0.232). CONCLUSION: A gastrectomy appears to be a risk factor of GB dysmotility, which may play a major role in gallstone formation in gastrectomized patients.
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BACKGROUND: Multiple antibiotic sensitivity syndrome with adverse drug reactions to multiple classes of antibiotics has been described in adults but is not well characterized in children. PATIENTS AND METHODS: Charts of children referred to the adverse drug reaction clinic at the Children's Hospital of Western Ontario, London, Ontario, with adverse drug reactions to multiple antibiotics were reviewed to determine the number of patients with adverse drug reactions to multiple classes of antibiotics and the clinical characteristics of the adverse events. RESULTS: The records of 97 children who were selected as possible candidates for multiple antibiotic sensitivity were studied. These records constituted 11% of referrals to a highly specialized adverse drug reaction clinic, suggesting that in usual clinical practice, this entity, if it does indeed constitute a distinct clinical entity, is quite uncommon. Age at time of the first adverse drug reaction was 26.1+/-26.3 (mean +/- SD) months. Among the 97 children, adverse reactions to five classes of antibiotic were noted in 3.1%, to four in 10.3%, to three in 47. 4% and to two in 39.2%. Most children (85.6%) experienced an adverse reaction to a penicillin, while 71.1% reacted to a cephalosporin, 80. 4% to a sulphonamide and 35.1% to a macrolide. Clinical presentations of the adverse reactions included urticaria or pruritus, other rash, serum sickness-like reaction, angioedema or anaphylaxis, erythema multiforme or Stevens-Johnson syndrome. CONCLUSIONS: There are children who have what appears to be immunologically mediated adverse drug reactions to antibiotics of multiple classes. These reactions, which most commonly manifest as urticaria or other rashes, follow drug use patterns. It remains to be defined whether this is a distinct clinical syndrome or a manifestation of a more fundamental problem in dealing with xenobiotics in the setting of infection. Further work on the immunological and/or biochemical determinants of the multiple antibiotic sensitivity syndrome (MASS) is needed to understand the pathophysiology and determinants of MASS and whether MASS constitutes a distinct clinical entity.
Guanylyl cyclases are a family of enzymes that catalyze the conversion of GTP to cGMP. The family comprises both membrane-bound and soluble isoforms that are expressed in nearly all cell types. They are regulated by diverse extracellular agonists that include peptide hormones, bacterial toxins, and free radicals, as well as intracellular molecules, such as calcium and adenine nucleotides. Stimulation of guanylyl cyclases and the resultant accumulation of cGMP regulates complex signaling cascades through immediate downstream effectors, including cGMP-dependent protein kinases, cGMP-regulated phosphodiesterases, and cyclic nucleotide-gated ion channels. Guanylyl cyclases and cGMP-mediated signaling cascades play a central role in the regulation of diverse (patho)physiological processes, including vascular smooth muscle motility, intestinal fluid and electrolyte homeostasis, and retinal phototransduction. Topics addressed in this review include the structure and chromosomal localization of the genes for guanylyl cyclases, structure and function of the members of the guanylyl cyclase family, molecular mechanisms regulating enzymatic activity, and molecular sequences coupling ligand binding to catalytic activity. A brief overview is presented of the downstream events controlled by guanylyl cyclases, including the effectors that are regulated by cGMP and the role that guanylyl cyclases play in cell physiology and pathophysiology.
This paper uses findings from the Maori section of a multiethnic infant care practices (ICP) study undertaken in Auckland, New Zealand/Aotearoa, in 1998. It aims to increase understanding of present day Maori infant care practices in order, firstly, to inform infant health message and service delivery to Maori and, secondly, to understand the context of practices that comprise modifiable risk factors for SIDS. Publicity about modifiable SIDS risk factors since the early 1990s brought about a significant reduction in the national SIDS rate but the Māori rate reduced more slowly and in 1998 was still three times that of non-Māori. The ICP study was a qualitative study that, for the Māori section, involved seven focus groups and a one-on-one interview comprising 26 caregivers of under 12 month old infants. This paper focuses on five selected areas explored within the ICP study: sources of support, customary practices, infant feeding, infant sleeping arrangements and smoking. It discusses both valued infant care norms and factors that inhibit changes known to reduce SIDS risk. It argues that valued practices need recognition in order to make messages effective. It also challenges the emphasis on individual behaviour change as the primary means to reduce SIDS risk and argues that there is a need to extend prevention strategies beyond simple behaviour change messages to include structural change to reduce 'non modifiable' risk factors.
BACKGROUND: Patients with stage II colorectal cancer and no histologic evidence of lymph node invasion develop recurrent disease, presumably because of undetected micrometastases. Guanylyl cyclase C is expressed by intestinal and colorectal cancer cells but not by extraintestinal tissues or tumors. OBJECTIVE: To examine the expression of guanylyl cyclase C messenger RNA (mRNA) in lymph nodes of patients with node-negative colorectal cancer who did and did not have recurrent disease. DESIGN: Case-control study. SETTING: Tertiary care academic medical center. PATIENTS: Paraffin-embedded lymph nodes were obtained from 21 patients with histologically confirmed node-negative colorectal cancer who had undergone resection. Controls included 11 patients without disease recurrence 6 or more years after resection, and case-patients included 10 patients whose disease recurred up to 3 years after resection. MEASUREMENTS: Sections of paraffin-embedded lymph nodes were obtained from each patient and were pooled, and their RNA was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Guanylyl cyclase C mRNA was expressed in lymph nodes from all patients with recurrent disease but not in those from patients without recurrent disease (P = 0.004). Nested RT-PCR that used primers for carcinoembryonic antigen, a marker for colorectal cancer, identified carcinoembryonic antigen mRNA in lymph nodes from only 1 of 10 patients with recurrent disease and those from 0 of 11 patients without recurrent disease. The odds ratio for death associated with expression of guanylyl cyclase C mRNA in regional lymph nodes was 15.0 (95% CI, 1.1 to 756.7). CONCLUSIONS: Expression of guanylyl cyclase C mRNA in lymph nodes is associated with recurrence of colorectal cancer in patients with stage II disease. Analysis of guanylyl cyclase mRNA expression by RT-PCR may be useful for colorectal cancer staging.
This article is concerned with the reliable search for optimally performing BSB (brain state in a box) neural associative memories given a set of prototype patterns to be stored as stable equilibrium points. By converting and/or modifying the nonlinear constraints of a known formulation for the synthesis of BSB-based associative memories into linear matrix inequalities, we recast the synthesis into semidefinite programming problems and solve them by recently developed interior point methods. The validity of this approach is illustrated by a design example.
2-Bromopropane and hydrochlorofluorocarbons (HCFCs), whose toxicity has scarcely been known, have recently been introduced as main substitutes for chlorofluorocarbons (CFCs). A major corporation in Korea replaced CFCs with 2-bromopropane and this actually led 23 Korean workers to be the world's first 2-bromopropane intoxication victims. Out of 25 female workers in the tactile switch assembling section, 17 (68%) were diagnosed as having ovarian failure. Two affected female workers showed marked pancytopenia with markedly hypoplastic marrow. In the same section, two out of eight male workers showed azoospermia and four some degree of oligospermia. The above toxicity of 2-bromopropane was reproduced in experimental animal studies. Recently, health effects of HCFC 123, including toxic hepatitis, have been reported by several authors. The principle of replacement of toxic substances with non-toxic or less toxic chemicals is important in risk management, but substances still poorly known should not be confused with non-toxic or less toxic substances. Measures aimed at reducing exposure to chemicals with known toxicity rather than using new unknown alternatives may be a rational and effective approach to risk management.