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Biomedical subjects

K A Lee

Publications and source records attributed to K A Lee.

At least 37 records · Page 2Linked to original sources
PubMed2000

The cellular oncogene EWS/activating transcription factor 1 is unable to activate adenovirus-borne promoters: implications for cytotoxic prodrug therapy of malignant melanoma of soft parts.

The cellular oncoprotein Ewing's sarcoma oncogene (EWS)/activating transcription factor 1 (ATF1) is a highly specific marker for malignant melanoma of soft parts (MMSP) and is a potent activator of several cAMP-inducible promoters, including the somatostatin promoter. Here we explored the potential for using the somatostatin promoter to direct toxic gene expression in MMSP cells. When introduced into MMSP cells, a somatostatin-herpes simplex virus thymidine kinase fusion gene confers strong and cell-specific sensitivity to the cytotoxic prodrug ganciclovir. Ganciclovir sensitivity requires the ATF-binding site present in the somatostatin promoter, indicating that toxic gene expression is caused by EWS/ATF1. We also tested the efficacy of recombinant adenoviruses adenoviruses for gene delivery and expression in two MMSP cell lines (DTC1 and Su-ccs-1). Surprisingly, several promoters (including somatostatin) that are strongly activated by EWS/ATF1 in transient assays are not activated in DTC1 and Su-ccs-1 cells when present in an adenovirus vector. In summary, our findings demonstrate the potential for using the somatostatin promoter for cytotoxic prodrug therapy for MMSP. However, first-generation adenovirus vectors cannot be used as promoter delivery vehicles for toxic gene expression in MMSP cells.

Adenoviridae↗
PubMed2000

Owls, larks and the significance of morningness/eveningness rhythm propensity in psychiatric-mental health nursing.

In the last decade there has been an upsurge in the research focusing on the interplay between the human circadian timing system and behavioral patterns in health and illness. Of particular interest in this area of inquiry is the overlay of what has been termed chronotype. What this refers to is the propensity of biological rhythms to express themselves in certain patterns of behavior. Commonly, these patterns have received names such as owl (evening chronotype) or lark (morning chronotype). Many people are neither a strong morning nor evening chronotype. If illness represents a change in the way a person's body functions within a given environment, then it is reasonable to believe that an "owl's" symptom presentation may vary significantly from the patterns of a "lark" who becomes ill. Recognizing that psychiatric nurses at both the generalist and the advanced practice levels have a strong interest in patterns of behavior, it stands to reason that using a lens that incorporates notions of the body's clock becomes essential. The interplay between the body's timing system and the thousands of other psychobiological rhythmic functions occurring everyday and within every human being is referred to as chronobiology. This article provides a primer for psychiatric nurses on issues of chronobiology related to morningness and eveningness rhythm propensity.

Affect↗
PubMed2000

Glucosidase inhibitor from Umbilicaria esculenta.

Inhibitory activity toward beta-glucosidase was detected in extracts of the lichen, Umbilicaria esculenta. The extract showed strong inhibition of disaccharide hydrolytic enzymes of mold and mammalian origin, but weak or no inhibition of polysaccharide hydrolytic enzymes except glucoamylase and laminarinase. The inhibitor in the extract was very stable, retaining more than 95% of its activity when treated with heat, acid, alkali, and some hydrolytic enzymes. Purified inhibitor was identified as 1-deoxynojirimycin (1,5-dideoxy-1,5-immino-D-glucitol) by NMR spectrometry, which was known to be produced by Streptomyces sp. and the plant Morus sp. Extracts from Parmelia austrosinensis, Parmelia praesorediosa, and an unidentified lichen species, showed glucosidase inhibitory activities similar to U. esculenta.

1-Deoxynojirimycin↗
PubMed1999

Sudden death due to ischaemic heart disease in young aboriginal sportsmen in the Northern Territory, 1982-1996.

OBJECTIVE: To estimate the incidence of sport-related sudden cardiac death due to ischaemic heart disease (IHD) in competitive young Aboriginal sportsmen. SETTING: Northern Territory (NT), 1982-1996. DESIGN: Retrospective case series with cases identified from Australian Bureau of Statistics cause-of-death listings and NT coronial autopsy records. MAIN OUTCOME MEASURES: Circumstances and incidence of sport-related sudden cardiac deaths due to IHD; autopsy findings. RESULTS: Between 1982 and 1996, there were eight sudden cardiac deaths due to IHD and related to sporting activity among Aboriginal sportsmen aged 15-37 years in the NT. Six were associated with games of Australian (rules) football. All occurred in the Top End of the NT in the wet season, and all occurred after the first half, or within an hour of, a game. Four of the players had macrosopic myocardial abnormalities (hypertrophy or previous infarcts) on autopsy. The estimated incidence of IHD-related sudden cardiac death among Aboriginal Australian football players in the NT was 19-24 per 100,000 player-years, compared with 0.54 per 100,000 player-years among Australian rules footballers of similar ages in Victoria. CONCLUSIONS: Incidence of sudden cardiac death attributable to underlying IHD was extremely high among young NT Aboriginal Australian footballers. Prevention will best be achieved by funding culturally appropriate long-term strategies to reduce the incidence of IHD. However, in the short-term, community-controlled programs with education of athletes, heat-stress reduction strategies, and cardiovascular screening should reduce the incidence of sudden cardiac death in sport.

Adult↗
PubMed1999

Left ventricular fibroma masquerading as postinfarction myocardial rupture.

A large left ventricular fibroma was encountered perioperatively for what was presumed to be a sealed ventricular rupture after thrombolytic therapy for an acute myocardial infarction. We review the pertinent literature concerning the diagnosis of ventricular rupture and this rare benign tumor of the heart.

Adult↗
PubMed1999

Cultural competence of measurement scales of menopausal symptoms: use in research among Korean women.

Even though there are advancements in research related to culturally competent care, there is an increasing realization that coherent theories and a research base to guide health care that is culturally competent is yet to be fully developed. In this paper, cultural competence of the scales measuring menopausal symptoms are critically analyzed in light of their limitations for Korean women--a population other than for whom it was developed. The analyses indicate that there are issues of contextuality, relevance, communication style, authenticity, power relationships and time constraints.

Cultural Characteristics↗
PubMed1999

Pain, fatigue, and sleep disturbances in oncology outpatients receiving radiation therapy for bone metastasis: a pilot study.

Pain and fatigue are two of the most common problems experienced by oncology patients. This study evaluated 24 oncology patients who were receiving radiation therapy for bone metastases to (1) describe the patterns of pain intensity and fatigue severity over a 48-hour period; (2) evaluate for sleep disturbances; (3) describe the relationships between these symptoms and various treatment characteristics; and (4) describe the self-care strategies used by patients to manage pain and fatigue. Patients reported moderate amounts of pain and fatigue. Average pain scores did not vary significantly over a 48-hour period. However, patients reported significantly lower fatigue scores in the morning compared to the evening. In addition, patients experienced significant sleep disturbances, with a mean sleep efficiency index of 70.7% (estimated using wrist actigraphy). Patients with lower Karnofsky Performance Status scores reported more sleep disturbances. In addition, patients who had received a higher percentage of their radiation treatment reported more sleep disturbances. Patients used a variety of self-care strategies to manage pain and fatigue. Additional research is warranted to describe more completely the patterns of pain, fatigue, and sleep disturbances in oncology outpatients receiving radiation therapy.

Adult↗
PubMed1999

Gender differences in sleep patterns for early adolescents.

PURPOSE: To describe gender differences in self-reported sleep disturbances and daytime sleepiness in an urban sample of early adolescents (11-14 years of age). METHODS: One hundred and forty-four racially diverse sixth- to eighth-grade students responded to an investigator-developed sleep questionnaire. Variables included school night and weekend sleep patterns as well as factors that influence sleep and daytime sleepiness, such as sleep/wake routine and alcohol and caffeine consumption. RESULTS: Boys consumed significantly more caffeinated beverages than girls, but this did not correlate with self-reports of waking after sleep onset. Caffeine intake was significantly related to self-reported parasomnias. Significant gender differences were found for self-reports of daytime sleepiness. There were also large variations between weekday and weekend sleep schedules. Weekday wakeup time for boys was significantly later compared to girls. Those who reported consumption of alcohol during the past week were likely to fall asleep in the classroom before lunch. Girls, who awakened earlier than boys on school days, were more likely to report falling asleep on the way home from school. CONCLUSIONS: These descriptive data support the need for further investigation into the relationship between caffeine intake and parasomnias, as well as into the observed gender differences.

Adolescent↗
PubMed1999

Sleep patterns of sheltered battered women.

PURPOSE: To describe sheltered battered women's sleep patterns and resulting daytime fatigue. The model for symptom management framed this study to describe one component of the model--symptom experience. Beginning evidence suggests that sheltered battered women experience disturbed sleep and fatigue that can interfere with vital activities. DESIGN: Descriptive using a convenience sample of 50 ethnically diverse women residing at least 21 days in battered women's shelters located in one western U.S. city. The study was done in 1997. METHODS: The Pittsburgh Sleep Quality Index (PSQI), the Mini Motionlogger Actigraph, a sleep diary, the Visual Analogue Scale for Fatigue, and an open-ended interview were used to collect data. Descriptive and inferential statistics were used to analyze the quantitative data. Qualitative data were analyzed to determine patterns and themes. FINDINGS: Seventy percent of the women had global PSQI scores of greater than five indicating poor sleep and 17 (34%) had a sleep efficiency index of 80% or less. Fourteen (28%) of the women went to bed very fatigued (> 66 mm) and 20 (40%) woke up very fatigued (> 33 mm). CONCLUSIONS: The majority of sheltered battered women experienced disturbed sleep and daytime fatigue. Both personal and environmental variables were found to significantly affect sleep patterns. Sheltered battered women can benefit from information about sleep disturbances and sleep enhancing self-care strategies.

Adult↗
PubMed1999

Herpes simplex virus type 1 vector-mediated expression of nerve growth factor protects dorsal root ganglion neurons from peroxide toxicity.

Nerve growth factor beta subunit (beta-NGF) transgene delivery and expression by herpes simplex virus type 1 (HSV-1) vectors was examined in a cell culture model of neuroprotection from hydrogen peroxide toxicity. Replication-competent (tk- K mutant background) and replication-defective (ICP4(-);tk- S mutant background) vectors were engineered to contain the murine beta-NGF cDNA under transcriptional control of either the human cytomegalovirus immediate-early gene promoter (HCMV IEp) (e.g., KHN and SHN) or the latency-active promoter 2 (LAP2) (e.g., KLN and SLN) within the viral thymidine kinase (tk) locus. Infection of rat B103 and mouse N2A neuronal cell lines, 9L rat glioma cells, and Vero cells with the KHN or SHN vectors resulted in the production of beta-NGF-specific transcripts and beta-NGF protein reaching a maximum at 3 days postinfection (p.i.). NGF protein was released into the culture media in amounts ranging from 10.83 to 352.86 ng/ml, with the highest levels being achieved in B103 cells, and was capable of inducing neurite sprouting of PC-12 cells. The same vectors produced high levels of NGF in primary dorsal root ganglion (DRG) cultures at 3 days. In contrast to HCMV IEp-mediated expression, the LAP2-NGF vectors showed robust expression in primary DRG neurons at 14 days. The neuroprotective effect of vector produced NGF was assessed by its ability to inhibit hydrogen peroxide-induced neuron toxicity in primary DRG cultures. Consistent with the kinetics of vector-mediated NGF expression, HCMV-NGF vectors were effective in abrogating the toxic effects of peroxide at 3 but not 14 days p.i. whereas LAP2-NGF vector transduction inhibited apoptosis in DRG neurons at 14 days p.i. but was ineffective at 3 days p.i. Similar kinetics of NGF expression were observed with the KHN and KLN vectors in latently infected mouse trigeminal ganglia, where high levels of beta-NGF protein expression were detected at 4 wks p.i. only from the LAP2; HCMV-NGF-driven expression peaked at 3 days but could not be detected during HSV latency at 4 weeks. Together, these results indicate that (i) NGF vector-infected cells produce and secrete mature, biologically active beta-NGF; (ii) vector-synthesized NGF was capable of blocking peroxide-induced apoptosis in primary DRG cultures; and (iii) the HCMV-IEp functioned to produce high levels of NGF for several days; but (iv) only the native LAP2 was capable of long-term expression of a therapeutic gene product in latently infected neurons in vivo.

Animals↗
PubMed1999

Symptom experience during menopausal transition: low income Korean immigrant women.

The symptoms experienced during menopausal transition of a vulnerable group of women, low income Korean immigrants, are described in this paper. The findings demonstrated that (a) the types of the symptoms that the women reported were different from those reported by Western women; (b) the women tended to normalize their symptoms; and (c) their symptom experience was influenced by immigration transition and its contextual variables. We suggest that symptom experience of immigrant women during menopausal transition be understood within the contexts of their immigration transition, and that their own views of normality of the menopausal transition be respected.

Adaptation, Psychological↗
PubMed1998

The EWS/ATF1 fusion protein contains a dispersed activation domain that functions directly.

Naturally occurring chromosomal fusion of the Ewings Sarcoma Oncogene (EWS) to distinct cellular transcription factors, produces aberrant transcriptional activators that function as dominant oncogenes. In Malignant Melanoma of Soft Parts the N-terminal region of EWS is fused to C-terminal region of the cAMP-inducible transcription factor ATF1. The EWS/ATF1 fusion protein binds to ATF sites present in cAMP-responsive promoters via the ATF1 bZIP domain and activates transcription constitutively in a manner that is dependent on an activation domain (EAD) present in EWS. To further define the requirements for trans-activation we have performed mutational analysis of EWS/ATF1 in mammalian cells and report several new findings. First, trans-activation by EWS/ATF1 does not require dimerisation with other ATF family members present in mammalian cells. Second, in contrast to the earlier suggestion of an allosteric role, the EAD can act directly. Third, determinants of trans-activation are dispersed throughout the EAD and cooperate synergistically to produce potent trans-activation. We also report that the region of EWS containing the EAD can activate transcription in Yeast. This latter finding might enable a genetic approach to understanding the mechanism of transcriptional activation by EWS and development of high-throughput screens for EWS inhibitors.

Amino Acid Sequence↗
PubMed1998

MMSP tumor cells expressing the EWS/ATF1 oncogene do not support cAMP-inducible transcription.

Malignant Melanoma of Soft Parts (MMSP) is associated with the EWS/ATF1 fusion protein that arises due to chromosomal fusion of the Ewings Sarcoma oncogene (EWS) and the cellular transcription factor ATF1. EWS/ATF1 can activate several cAMP-inducible promoters, suggesting that cellular transformation in MMSP might involve constitutive activation of cAMP-inducible promoters. To assess this possibility we have examined the status of the cAMP-signaling pathway in the available MMSP-derived cell lines (DTC1 and Su-ccs-1) and find that both cell lines share several features. First, in contrast to previous effects observed in transient assays, three chromosomal promoters containing ATF binding sites are not constitutively activated by endogenous EWS/ATF1 in MMSP cells. Second, all the components that are known to be required for cAMP-inducible transcription are present. Third, phosphorylation of the cAMP-response-element-binding protein (CREB) can be efficiently induced by cAMP. Fourth, cAMP is unable to activate transcription, as assessed by a GAL4/ATF1 reporter assay and analysis of the c-fos and adenovirus early promoters. Thus, cell lines derived from MMSP have a block to cAMP-signaling that lies downstream of CREB phosphorylation. In light of the cAMP-responsiveness of almost all mammalian cell types, our findings suggest that the inability to respond to cAMP might be an important feature of MMSP cells.

Activating Transcription Factor 1↗
PubMed1998

Two steroidogenic pathways present in the chicken ovary: theca layer prefers delta 5 pathway and granulosa layer prefers delta 4 pathway.

It has been suggested that there is a shift in steroidogenic pathways of the theca layer from delta 5 to delta 4 during follicular maturation in the chicken ovary. However, the preferred steroid metabolic pathway in the theca and granulosa layers of small and preovulatory follicles has not been identified. Therefore, the goal of our study was to identify the preferred steroidogenic pathways used by these follicles. Previously, we found that small follicles that had not entered the follicular hierarchy did not use cholesterol but did use pregnenolone (P5) to produce testosterone and estradiol. For this reason, P5 was used as the substrate for steroid production in the present study. The theca layer of small follicles (2-4 mm in diameter), and the theca and granulosa layers of the fifth largest (F5), third largest (F3), and largest (F1) preovulatory follicles were isolated from the chicken ovary 22 hr before ovulation. The granulosa layer of small follicles was excluded from the study because it is steroidogenically incompetent. Tissues were incubated with [3H]-P5 for 1 hr at 37 degrees C. Production of steroid metabolites was determined on the basis of comparison with known steroid standards using two-dimensional thin layer chromatography (2D-TLC). Conversion of [3H]-P5 to [3H]-DHEA was greater than that of [3H]-P4 in the theca layer of small and preovulatory follicles. Even though the amount of [3H]-P4 was less than that of [3H]-DHEA, theca cells from F3 and F1 follicles did produce [3H]-P4. In contrast to the theca layer, conversion of [3H]-P4 was greater than that of [3H]-DHEA in the granulosa layer of preovulatory follicles. Conversion of [3H]-P5 to [3H]-DHEA by the granulosa layer gradually decreased as the follicle matured and approached ovulation. We conclude that both delta 5 and delta 4 pathways are functional in theca and granulosa cells. However, in contrast to earlier speculation, the theca layer preferentially metabolizes steroids via the delta 5 pathway regardless of the maturational stage of the follicle, whereas the granulosa layer of preovulatory follicles preferentially metabolizes steroids via the delta 4 pathway.

Animals↗
PubMed1998

The Hispanic teen mother's origin of birth, use of prenatal care, and maternal and neonatal complications.

The purpose of this study was to describe and compare differences in demographics, prenatal care use, and pregnancy, labor, postpartum, and neonatal complications for 129 pregnant Mexican-American adolescents who were either born in the United States or born in Mexico. A significant finding was that 25% of the teens, regardless of origin of birth, received either inadequate or no prenatal care. The findings of this study will be useful to clinicians providing health care for Hispanic teens and for administrators and policy makers who affect the types of health care and education available to these young mothers.

Adolescent↗
PubMed1998

Alterations in sleep during pregnancy and postpartum: a review of 30 years of research.

Pregnancy, childbirth, and early motherhood physiologically and psychologically affect a woman's sleep. Hormonal alterations during early pregnancy, enlargement of the fetus during late pregnancy, and a newborn with random sleep-wake patterns all contribute to disrupted sleep. Since the initial study of sleep and pregnancy in 1968, fewer than 20 articles have been published which address alterations in sleep architecture related specifically to childbearing women. Furthermore, many of these studies suffer from small sample sizes and lack statistical power for consistent interpretation and replication of findings. While almost all of these studies included both nulliparas and multiparas in their samples, rarely have effects of parity been reported. The majority of older studies were cross-sectional designs, with comparisons to age-matched healthy controls. More recent studies have been longitudinal designs to describe changes in sleep during the course of pregnancy. However, women's baseline, prepregnancy sleep patterns or sleep histories have not been considered. With very few published reports of sleep changes related to mental health outcomes, we are no closer to understanding the implications of altered sleep patterns on postpartum depression or other women's health outcomes than we were when it was originally questioned 30 years ago.

Journal Article↗