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Biomedical subjects

E Park

Publications and source records attributed to E Park.

At least 37 records · Page 2Linked to original sources

The Adolescent Health Review: a brief, multidimensional screening instrument.

PURPOSE: To develop a brief, multidimensional screening instrument for adolescents that addresses psychosocial domains critical to adolescent preventive health care services. METHODS: Secondary analyses were conducted on survey data obtained in 1995 from a school sample of 76,159 students in grades 9 and 12, as well as 893 adolescents from juvenile correctional facilities, 500 adolescents from chemical dependency treatment programs, and 575 adolescents from residential behavioral treatment programs. A comprehensive set of 300 survey items was used in a series of discriminant analyses to determine which items best distinguished males and females in each clinical sample from their counterparts in the school sample. RESULTS: The item selection for the Adolescent Health Review was guided both by empirical analyses and clinical judgment. The final screen is comprised of 33 demographic and clinical items that address a variety of psychosocial domains. The computerized, self-administered screen can be completed in about 3 minutes. The screen is scored automatically and produces an easy-to-read risk-assessment profile. Because screening items were drawn from a large epidemiologic survey, normative profiles are available for each age and gender subgroup. CONCLUSIONS: A brief, empirically derived screening instrument, designed to address a range of adolescent risks, offers an opportunity for information gathering that otherwise might not be incorporated into routine clinic visits.

Adolescent↗

Mental practice effect on line-tracing accuracy in persons with hemiparetic stroke: a preliminary study.

OBJECTIVE: To investigate the effect of mental practice on line-tracing accuracy of persons with hemiparetic stroke. DESIGN: A single-case, experimental, multiple baseline design. SETTING: Electromyography laboratory of a rehabilitation medicine department of a university hospital. PARTICIPANTS: Three persons with right hemiparesis from stroke. INTERVENTION: Mental practice for line-tracing training. MAIN OUTCOMES MEASURES: Two tracing tasks were used to evaluate the effect of mental practice: (1) tracing a 5.9-inch long horizontal line (task 1); and (2) tracing a 6-inch long curved line (task 2) as a generalization probe. Participants were first trained to master the cognitive rehearsal skill by checking the reduction level of tension in their upper trapezius while listening to a relaxation cassette tape. Second, participants were trained to trace task 1 immediately after listening to a cognitive rehearsal tape that contained the command to trace over a horizontal line as accurately as possible. Then, without the cognitive rehearsal process, participants traced over a curved line as a generalization probe. The dependent variable, called the line length error, was the total distance that the traced line deviated from the printed lines (both horizontal and curved). RESULTS: Mean-line length errors of participants 1, 2, and 3 were: horizontal line tracing, 3.33, 7.38, and.30 inches, respectively, in the baseline and 1.41, 2.70, and.24 inches, respectively, after mental practice training. With the curved line tracing, mean length errors were 3.15, 6.56, and.52 inches in the baseline and 1.85, 4.36, and.80 inches postintervention, respectively. CONCLUSIONS: Mental practice can be an effective method to improve line tracing by persons with hemiparetic stroke. Training in horizontal line tracing showed a modest level of generalization to curved line tracing.

Activities of Daily Living↗

Prospective study of fibrinolytic factors and incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study.

The fibrinolytic system may play a role in the pathogenesis of coronary heart disease (CHD), but existing prospective studies have not consistently shown an independent association between fibrinolytic factors and CHD. None has reported an association between plasminogen and CHD incidence. In the prospective Atherosclerosis Risk in Communities (ARIC) Study of middle-aged adults, we examined the association of incident CHD with several fibrinolytic factors: tissue plasminogen activator antigen, plasminogen activator inhibitor-1, plasminogen, and fibrin fragment D-dimer as well as a marker of coagulation activation (prothrombin fragment F1.2). We measured these in stored baseline plasma samples of 326 subjects who developed CHD and, for comparison, a stratified random sample of the entire cohort (n=720). Tissue plasminogen activator and plasminogen activator inhibitor-1 antigen levels were associated positively with CHD incidence in analyses adjusted for age, race, and sex but were not associated with CHD after adjustment for other risk factors. Plasminogen and D-dimer levels were associated positively and independently with CHD incidence; the multivariable-adjusted relative risks (95% CIs) for the highest versus lowest quintiles were 2.20 (1.2 to 4.2) for plasminogen and 4.21 (1.9 to 9.6) for D-dimer. F1.2 was not associated with CHD incidence. Our findings lend support for a link between fibrinolytic factors and CHD incidence. A positive association between plasminogen and CHD is seemingly opposite the direction expected but may reflect a compensatory response to impaired plasminogen activation in subjects prone to CHD.

Biomarkers↗

Declining insulin requirement in the late first trimester of diabetic pregnancy.

OBJECTIVE: To investigate whether pregnancies complicated by type 1 diabetes are associated with a decrease in first-trimester insulin requirement. RESEARCH DESIGN AND METHODS: We examined the weekly insulin requirement (as units per kilogram per day) during the first trimester of pregnancy in diabetic women in the Diabetes in Early Pregnancy Study (DIEP) with accurate gestational dating, regular glucose monitoring, daily insulin-dose recording, and monthly glycohemoglobin measurements. RESULTS: In pregnancies that resulted in live-born full-term singleton infants, a significant 18% increase in mean weekly dosage was observed between weeks 3 and 7 (P = 0.000), followed by a significant 9% decline from week 7 through week 15 (P = 0.000). Further testing localized a significant change in insulin dose in the interval beginning weeks 7-8 and ending weeks 11-12 (P = 0.014). Within this interval, the maximum decrease was between weeks 9 and 10 (mean), 10 and 11 (median), and 8 and 9 (most frequent maximal decrease). To determine whether prior poor glucose control exaggerated these trends, we categorized the women based on their glycohemoglobin values: <2 SDs above the mean of a normal population (subgroup 1), 2-4 SDs (subgroup 2), and >4 SDs (subgroup 3) at baseline. Late first-trimester declines in dosage were statistically significant in subgroup 2 (P = 0.002) and subgroups 2 and 3 together (P = 0.003). Similarly, women with BMI >27.0 had a greater initial insulin rise and then fall compared with leaner women. CONCLUSIONS: Observations in the DIEP cohort disclose a mid-first-trimester decline in insulin requirement in type 1 diabetic pregnant women. Possible explanations include overinsulinization of previously poorly controlled diabetes, a transient decline in progesterone secretion during the late first-trimester luteo-placental shift in progesterone secretion, or other hormonal shifts. Clinicians should anticipate a clinically meaningful reduction in insulin requirement in the 5-week interval between weeks 7 and 12 of gestation.

Adolescent↗

Pentoxifylline downregulates nitric oxide and tumor necrosis factor-alpha induced by mycobacterial lipoarabinomannan in a macrophage cell line.

Pentoxifylline (PTX), a phosphodiesterase inhibitor, is known to downregulate tumor necrosis factor-alpha (TNF-alpha) secretion induced by lipopolysacchride (LPS) and gamma interferon (IFN-gamma). We have had limited success in treating leprosy reactions, including erythema nodosum leprosum (ENL), in which TNF-alpha has been identified as a major proinflammatory cytokine. PTX inhibited production of NO (IC50 approximately equal to 1.0 mg/ml) and TNF-alpha (IC50 approximately equal to 0.05 mg/ml) in a dose-dependent fashion. As little as 0.5 mg/ml of PTX decreased NO production and 0.01 mg/ml of PTX inhibited TNF-alpha production. Western blot analyses demonstrated that iNOS was suppressed by PTX. Northern blot analyses showed significant reduction of TNF-alpha mRNA. We conclude that PTX is an effective inhibitor of lipoarabinomannan (LAM)-induced TNF-alpha production at both the product and transcriptional levels in our macrophage cell line. PTX also showed moderate inhibition of NO at the product level as well as translation of iNOS.

Animals↗

The AGAMOUS-LIKE 20 MADS domain protein integrates floral inductive pathways in Arabidopsis.

The very late-flowering behavior of Arabidopsis winter-annual ecotypes is conferred mainly by two genes, FRIGIDA (FRI) and FLOWERING LOCUS C (FLC). A MADS-domain gene, AGAMOUS-LIKE 20 (AGL20), was identified as a dominant FRI suppressor in activation tagging mutagenesis. Overexpression of AGL20 suppresses not only the late flowering of plants that have functional FRI and FLC alleles but also the delayed phase transitions during the vegetative stages of plant development. Interestingly, AGL20 expression is positively regulated not only by the redundant vernalization and autonomous pathways of flowering but also by the photoperiod pathway. Our results indicate that AGL20 is an important integrator of three pathways controlling flowering in Arabidopsis.

AGAMOUS Protein, Arabidopsis↗

Non-parametric test of ordered alternatives in incomplete blocks.

Often in medical studies, study subjects become a natural block of observations repeated over a time period. Some subjects miss observations, thus becoming incomplete blocks of observations. We are interested in testing an ordered alternative (or time trend), and propose a non-parametric method to detect a trend in incomplete blocks. Our approach is to estimate the trend by the linear regression method within each block and apply the one-sample Wilcoxon test to the estimated linear trends. The one-sample Wilcoxon test will be sensitive to the trend if it exists. The proposed test statistic is asymptotically normal and consistent. We can also estimate the overall magnitude of the linear trend and its confidence interval by a proper non-parametric method. By Monte Carlo studies, we compare the performance of the proposed test against extended Page and Jonckheere tests. Published in 2000 by John Wiley & Sons, Ltd.

Adult↗

Rb protein down-regulates the stress-activated signals through inhibiting c-Jun N-terminal kinase/stress-activated protein kinase.

The Rb protein is the product of the retinoblastoma susceptibility gene and loss of Rb function is detected in many types of human cancers. Rb plays important roles in the regulation of cell proliferation, differentiation, senescence, and apoptotic cell death. Here we show that Rb can physically interact with c-Jun NH(2)-terminal kinase/stress-activated protein kinase (JNK/SAPK), thereby inhibiting intracellular signals mediated by JNK/SAPK. Both in vitro binding and in vitro kinase studies suggest that a carboxyl-terminal domain of Rb containing amino acids 768-928 might be crucial for inhibiting JNK/SAPK. In comparison, Rb did not affect enzymatic activity of either extracellular signal-regulated kinase 1 or p38. Ectopically expressed Rb also abrogated the apoptotic cell death induced by ultraviolet radiation or the activation of MEKK1, an upstream kinase that can stimulate the JNK/SAPK cascade. JNK/SAPK inhibition highlights a novel function of Rb, which may provide a new mechanism by which Rb regulates cell death. JNK/SAPK is a major protein kinase that can be stimulated in response to a variety of cellular stresses. Our results, therefore, suggest that Rb, by inhibiting JNK/SAPK, may act as a negative regulator in stress-activated intracellular signaling cascades.

Apoptosis↗

Selenite inhibits the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) through a thiol redox mechanism.

Selenium, an essential biological trace element, has been shown to modulate functions of many regulatory proteins involved in signal transduction and to affect a variety of cellular activities including cell growth, survival, and death. The molecular mechanism by which selenium exerts its action on the cellular events, however, remains unclear. In our present study, we observed that selenite suppresses both the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and the p38 mitogen-activated protein kinase pathway in 293T cells. In contrast, selenite had little effect on the extracellular signal-regulated kinase pathway. Furthermore, selenite directly inhibited JNK/SAPK activity in vitro but not the p38 activity. The in vitro inhibition of JNK/SAPK by selenite was reversed by the addition of reducing agents such as dithiothreitol and beta-mercaptoethanol. Replacement of cysteine 116 in JNK1 by serine abolished the inhibitory effect of selenite on JNK1 activity both in vitro and in vivo. Selenite also suppressed a c-Jun-dependent luciferase reporter activity stimulated through the JNK signaling pathway. Taken together, our findings strongly suggest that selenite differentially modulates the mammalian mitogen-activated protein kinase pathways and that it can repress the JNK/SAPK signaling pathway by inhibiting JNK/SAPK through a thiol redox mechanism.

Base Sequence↗

Partial impairment of immune functions in peripheral blood leukocytes from aged men with Down's syndrome.

Down's syndrome (DS) has been considered a model of accelerated aging and of Alzheimer's disease. We investigated immunologic functions using peripheral blood leukocytes in order to correlate the production of cytokines and development of neuropathological changes of Alzheimer type in aged persons with DS. Cytokine production (IL-1beta, IL-2, IL-6, IL-8, and TNF-alpha), phytohemagglutinin (PHA)-stimulated proliferation of nonadherent monocytes, and superoxide anion production from polymorphonuclear leukocytes were measured. PHA-stimulated proliferation in aged individuals (>30 years old) with DS was significantly lower than that of age- and sex-matched controls (DS vs control, 55,707+/-5810 vs 88,310+/-6994 cpm, P < 0.001). PHA-stimulated IL-2 production was also significantly decreased in aged individuals with DS (DS vs control, 7.1+/-2.1 vs 10.7+/-1.3 ng/ml). Interestingly, the decrease of proliferation and IL-2 production in aged males with DS is significantly greater than in aged women with DS. PHA-stimulated proliferation and IL-2 production of nonadherent monocytes in females was not significantly reduced. IL-1beta production by LPS-activated adherent monocytes was significantly decreased in older adults with DS compared with non-DS controls. Other immune parameters measured in DS were not significantly different from that of age-matched controls. We conclude that there is partial impairment of T lymphocytes in aged persons with DS that is significantly greater in males than in females.

Adult↗

The relative importance of social versus commercial sources in youth access to tobacco, alcohol, and other drugs.

BACKGROUND: Youth substance use began to increase in 1992 following a decade-long decline, leading to increased interest in controlling access to tobacco, alcohol, and other drugs. METHODS: The anonymous and voluntary Minnesota Student Survey was administered to 133,794 public school students in grades 6, 9, and 12. Questions addressed current frequency of use of tobacco, alcohol, and other drugs and how students obtained these substances. Data were analyzed to determine the relationship between grade level, gender, race/ethnicity, use frequency, and access to substances through social and commercial sources. (Tobacco analyses were limited to students under age 18 years.) RESULTS: Social sources (especially friends) predominate across all age groups and substances. Students are much more likely to obtain tobacco than alcohol from commercial sources but few rely exclusively on commercial sources for either. Females and infrequent users are more likely to depend on social sources exclusively while males and frequent users are more likely to use commercial sources. CONCLUSIONS: Because substances are easily accessible through social sources, prevention policies directed at retail outlets may not have the desired effect on reducing teen smoking and drinking. Greater attention to reducing access to all substances from social sources is needed.

Adolescent↗

Urinary NMP22 and renal cell carcinoma.

OBJECTIVES: To demonstrate the incidence of positive urinary nuclear matrix protein 22 (NMP22) values associated with renal cell carcinoma (RCC) of the kidney. Currently, urinary NMP22 is used to detect recurrent transitional cell carcinoma of the bladder. METHODS: From May 1997 to March 1998, urinary NMP22 values were obtained from 65 patients who had undergone either computed tomography scanning of the abdomen or renal ultrasound. Of the 65, 32 presented with solid renal masses. These patients underwent radical or partial nephrectomy; subsequent pathologic examination revealed that 30 had RCC. Two patients had oncocytomas. The remaining 33 patients presented with blunt abdominal trauma or abdominal pain or for follow-up for a urologic problem (a kidney stone or benign renal cyst). These patients had no evidence of renal malignancy on imaging and were used as controls. RESULTS: The urinary NMP22 values of patients with RCC were significantly higher than the values found in the control group (13.69 +/- 8.40 U/mL versus 3.03 +/- 2.70 U/mL, P <0.0078). Of the 30 patients with RCC, 12 (40%) had positive urinary NMP22 values of 10 U/mL or above. Chi-square analysis revealed a significant difference between the NMP22 values of the two groups (P <0.005). There were two false-positive NMP22 values in the 35 control patients. CONCLUSIONS: Urinary NMP22 values used to detect transitional cell carcinoma in individuals with previously diagnosed bladder cancer should be more broadly evaluated, since elevations have also been found to occur in RCC of the kidney. This finding may result in an increase in the incidental discovery of RCC. Future, more specific, NMP assays may hold promise for the detection of RCC.

Biomarkers, Tumor↗

Characterization of a novel negative regulatory element in the human interleukin 4 promoter.

Interleukin 4 (IL-4) is a multifunctional cytokine that plays an important role in hematopoiesis, tumor cell growth, and cellular immune responses. Expression of the IL-4 gene is tightly controlled at the level of gene transcription, and many positive regulatory cis-elements have been identified in the proximal IL-4 promoter region. Relatively little is known about factors that downregulate IL-4 transcription. We performed a detailed deletional analysis of the proximal human IL-4 promoter and studied reporter gene activity in transiently transfected Jurkat T lymphoblasts. In this report, we characterize a novel negative regulatory element (termed P2 NRE) that is adjacent to a binding site for nuclear factor of activated T cells. Mutation of P2 NRE significantly enhanced the activity of a 175 base pair IL-4 promoter construct in transiently transfected Jurkat T lymphoblasts. Using nuclear extracts from Jurkat cells, we identify a candidate factor (termed Rep-1) that binds uniquely to the P2 NRE in DNA-binding assays. Rep-1 is not related to other factors previously shown to interact with the IL-4 promoter, and by UV cross-linking and SDS-PAGE analysis, we found that it migrates with a molecular mass of approximately 150 kDa. Characterizing the molecular mechanisms responsible for downregulating the IL-4 promoter should enhance our understanding of IL-4-gene dysregulation in disease states.

Binding Sites↗

Extracellular targeting of choline-binding proteins in Streptococcus pneumoniae by a zinc metalloprotease.

A genetic-based search for surface proteins of Streptococcus pneumoniae involved in adhesion identified a putative zinc metalloprotease (ZmpB). ZmpB shared high amino acid sequence similarities with IgA1 proteases of Gram-positive bacteria, but ZmpB had neither IgA1 nor IgA2 protease activity. Analysis of a family of surface-expressed proteins, the choline-binding proteins (Cbp's), in a zmpB-deficient mutant demonstrated a global loss of surface expression of CbpA, CbpE, CbpF and CbpJ. CbpA was detected within the cytoplasm. The zmpB-deficient mutant also failed to lyse with penicillin, a sign of lack of function of the Cbp LytA. Immunodetection studies revealed that the autolysin (LytA), normally located on the cell wall, was trapped in the cytoplasm colocalized with DNA and the transformation protein CinA. Trafficking of CinA and RecA to the cell membrane during genetic competence was also not observed in the zmpB-deficient mutant. These results suggest a protease dependent regulatory mechanism governing the translocation of CinA and the Cbp's LytA and CbpA of S. pneumoniae.

Alleles↗

Enhanced rate response algorithm for orthostatic compensation pacing.

Upon orthostatic stress after a period of rest, the heart rate increases rapidly to maintain cardiac output and minimize the fall in arterial pressure. Pacemaker patients are often prone to a deficient response to orthostatic stress. This may cause lightheadedness and, in rare patients with autonomic dysfunction, syncope. To alleviate these undesirable consequences, an enhanced rate response algorithm was developed using an accelerometer. The pacemaker generates two signals from its accelerometer: instantaneous activity level (Act) and long-term change in activity level (ActVar). Low values of both Act and ActVar indicate a resting state. An increase in Act while ActVar remains low indicates the onset of motion after prolonged rest. Upon detecting this transition, the algorithm increases the pacing rate to a programmable orthostatic compensation rate for a programmable duration. A taped-on pacemaker with this algorithm was evaluated in three healthy women and two healthy men, 36 +/- 8 years of age. Electrocardiogram and ventricular pacing pulses were recorded by a 24-hour ambulatory system. Each trigger of the orthostatic compensation rate was verified against a > 10 beats/min increase in heart rate, a response classified as appropriate. The overall specificity of the algorithm among the five subjects was 78%. The nocturnal specificity (10 PM to 7 AM) was 98%, considerably higher than during daytime (72%). In conclusion, a pacing algorithm to alleviate orthostatic stress was developed, which was highly specific during the night hours.

Acceleration↗