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Biomedical subjects

K A Lee

Publications and source records attributed to K A Lee.

At least 19 recordsLinked to original sources

Symptom experience and functional status among HIV-infected women.

Irrespective of powerful drug therapies, there has been a slight increase in newly diagnosed cases of AIDS in women. HIV/AIDS-related symptoms develop from the illness itself, treatments or medications. Symptoms and their reoccurrence remain problematic. This study is a secondary analysis of data exploring symptoms, symptom distress and functional status in 104 ethnically diverse HIV-positive women. Measures included the Brief Symptom Inventory, a General Symptom Questionnaire, the Center for Epidemiological Studies Depression Scale, and the Inventory of Functional Status. Findings indicate that this sample of women was distressed, at risk for depression and had a moderate level of physical functioning. These findings support the need for symptom management interventions that enhance emotional wellbeing and self-care activities for HIV-infected women.

Activities of Daily Living↗

Tandem translocation of chromosomes 22 and 15 with two preserved satellite stalk regions and deletion 22q13.3-qter.

We describe here a case of a tandem 22/15 translocation with deletion of the 22q13.3-qter region and retention of the NOR of chromosome 15. A 2(1/2)-year-old Korean girl was referred for chromosome analysis after a clinical evaluation for developmental delay. Physical examination revealed hypotonia, developmental delay, delay of gross motor milestones and speech delay. No dysmorphic features of face, hands or feet were evident in the patient. G-banded peripheral blood lymphocyte chromosomes showed a tandem translocation between chromosomes 22 and 15, with the satellite stalks of chromosome 15 apparently being retained. All-telomere FISH analysis using a TTAGGG repeat probe showed absent signals at the junction of the translocation. Sequential G-banding and FISH analysis using a beta satellite probe showed positive signals close to the junction of the translocation, an indication that the short arms of the chromosome 15 involved in the translocation are retained. FISH with a probe for arylsulfatase, mapped to 22q13.3 region, was negative on the translocation chromosome. Therefore, the 22q13.3 region is deleted.

Abnormalities, Multiple↗

Increased frequencies of glutathione S-transferase (GSTM1 and GSTT1) gene deletions in Korean patients with acquired aplastic anemia.

Patients with reduced ability to metabolize environmental carcinogens or toxins may be at risk of developing aplastic anemia. Glutathione S-transferase (GST) has been implicated in detoxifying mutagenic electrophilic compounds. This study asked whether the homozygous gene deletions of GSTM1 and GSTT1 affect the likelihood of developing aplastic anemia. The incidence of GSTM1 and GSTT1 gene deletions was significantly higher for aplastic anemia patients (odds ratio [OR]: 3.1, P =.01 and OR: 3.1, P =.004, respectively) than for healthy controls. Among the aplastic anemia patients, 17.5% (10:57) had chromosomal abnormalities at the time of diagnosis, and all aplastic anemia patients with chromosomal abnormalities showed GSTT1 gene deletions (P =.048). Individuals with GSTM1 and GSTT1 gene deletions may have greater susceptibility to aplastic anemia. It is possible that genetic instability or chromosomal damage due to abnormal detoxification of environmental toxins might have worked as an important pathophysiologic mechanism of aplastic anemia for patients with GSTT1 gene deletions.

Adolescent↗

Multiple phosphorylation of rhodopsin and the in vivo chemistry underlying rod photoreceptor dark adaptation.

Dark adaptation requires timely deactivation of phototransduction and efficient regeneration of visual pigment. No previous study has directly compared the kinetics of dark adaptation with rates of the various chemical reactions that influence it. To accomplish this, we developed a novel rapid-quench/mass spectrometry-based method to establish the initial kinetics and site specificity of light-stimulated rhodopsin phosphorylation in mouse retinas. We also measured phosphorylation and dephosphorylation, regeneration of rhodopsin, and reduction of all-trans retinal all under identical in vivo conditions. Dark adaptation was monitored by electroretinography. We found that rhodopsin is multiply phosphorylated and then dephosphorylated in an ordered fashion following exposure to light. Initially during dark adaptation, transduction activity wanes as multiple phosphates accumulate. Thereafter, full recovery of photosensitivity coincides with regeneration and dephosphorylation of rhodopsin.

Adaptation, Ocular↗

A repetitive element containing a critical tyrosine residue is required for transcriptional activation by the EWS/ATF1 oncogene.

Chromosomal fusion of the N-terminal region of the Ewings Sarcoma Oncogene (EWS-activation-domain, EAD) to the DNA-binding domains of a variety of cellular transcription factors produce oncogenic proteins (EWS-fusion proteins (EFPs)) that cause distinct malignancies. In EFPs, the EAD acts as a potent transcriptional activation domain and this ability is repressed in the context of normal, non-tumorigenic, EWS. Trans-activation by the EAD is therefore a specific characteristic of EFPs and it is thought that EFPs induce tumorigenesis via improper transcriptional activation of cellular genes. Functional elements required for transcriptional activation are dispersed throughout the EAD, as are thirty-one copies of a Degenerate Hexapeptide Repeat (DHR, consensus SYGQQS). This suggests that the EAD contains a highly reiterated functional element related to DHRs. Here we show that in the context of EWS/ATF1, the EFP that causes malignant melanoma of soft parts, trans-cooperation by small regions of the EAD ( approximately 30 residues) results in potent transcriptional activation dependent on the conserved tyrosine residues present in DHRs. These findings provide the first evidence for a role of DHRs in EAD-mediated trans-activation and demonstrate that the EAD represents a novel tyrosine-dependent transcriptional activation domain.

Amino Acid Sequence↗

Both E6 and E7 oncoproteins of human papillomavirus 16 inhibit IL-18-induced IFN-gamma production in human peripheral blood mononuclear and NK cells.

Cervical carcinoma is the predominant cancer among malignancies in women throughout the world, and human papillomavirus (HPV) 16 is the most common agent linked to human cervical carcinoma. The present study was performed to investigate the mechanisms of immune escape in HPV-induced cervical cancer cells. The presence of HPV oncoproteins E6 and E7 in the extracellular fluids of HPV-containing cervical cancer cell lines SiHa and CaSki was demonstrated by ELISA. The effect of HPV 16 oncoproteins E6 and E7 on the production of IFN-gamma by IL-18 was assessed. E6 and E7 proteins reduced IL-18-induced IFN-gamma production in both primary PBMCs and the NK0 cell line. FACS analysis revealed that the viral oncoproteins reduced the binding of IL-18 to its cellular surface receptors on NK0 cells, whereas there was no effect of oncoproteins on IL-1 binding to its surface IL-1 receptors on D10S, a subclone of the murine Th cell D10.G4.1. In vitro pull-down assays also revealed that the viral oncoproteins and IL-18 bound to IL-18R alpha-chain competitively. These results suggest that the extracellular HPV 16 E6 and E7 proteins may inhibit IL-18-induced IFN-gamma production locally in HPV lesions through inhibition of IL-18 binding to its alpha-chain receptor. Down-modulation of IL-18-induced immune responses by HPV oncoproteins may contribute to viral pathogenesis or carcinogenesis.

Adjuvants, Immunologic↗

An hsRPB4/7-dependent yeast assay for trans-activation by the EWS oncogene.

Chromosomal fusions of the N-terminal region of the Ewings Sarcoma Oncogene (EWS-Activation-Domain, EAD) to the DNA-binding domains of a variety of cellular transcription factors, produce oncogenic proteins (EWS-fusion proteins (EFPs)) that cause a variety of malignancies. The EAD can act as a potent transcriptional activation domain and is required for the oncogenic activity of EFPs. Previous studies demonstrating a physical interaction between the EAD and the human RNA Polymerase II subunit hsRPB7 suggest a crucial role for RPB7 and its partner, RPB4, in EAD function. Homologues of hsRPB4/7 exist in S. cerevisiae, and here we describe an RPB4/7-dependent yeast assay for EAD-mediated trans-activation. Conditional yeast strains lacking RPB4 are defective for trans-activation by a Gal4/EAD fusion protein at the permissive temperature. Introduction of hsRPB4 alone is unable to rescue trans-activation, while a combination of hsRPB4 and hsRPB7 significantly rescues activity. These findings provide the first functional evidence for a direct role of the RPB4/7 complex in EAD-mediated trans-activation. In addition, the yeast assay provides a tractable system for further molecular analysis of EAD and RPB4/7 action.

Genetic Techniques↗

Stereopsis in patients with albinism: clinical correlates.

PURPOSE: A hallmark of albinism is excessive decussation of retinostriate projections at the optic chiasm. This misprojection might lead to abnormalities in the retinal correspondence and may account for the usual absence of stereovision. We report on 2 groups of patients with albinism who have either fine or gross stereopsis and compare the clinical findings of these groups to other patients with albinism with similar visual acuities but no stereopsis. METHODS: A retrospective chart review of patients with albinism was used to segregate those with a letter visual acuity of 20/100 or better in one eye, assessment of stereopsis, and strabismus < or = 10 PD. Forty-five patients were identified. Albinism type, best-corrected visual acuity, motility, Titmus vectograph stereoacuity, iris and macula transparency grades, and the presence or absence of both melanin and an annular reflex in the macula were tabulated. A comparison of the clinical characteristics of the groups with and without stereopsis was made. RESULTS: Those albino subjects who demonstrated stereopsis had better visual acuity, less iris transillumination, more frequent presence of melanin in the macula, less nystagmus, and less marked foveal hypoplasia than the albino subjects without stereopsis. No nystagmus was clinically detected in 5 patients with fine stereopsis. All these differences were statistically significant. Macular transparency grade was not significantly different between the groups. CONCLUSIONS: Patients with albinism who demonstrate stereopsis tend to have better visual acuity, more iris pigment, and more melanin pigment in the macula than their counterparts without stereopsis.

Adolescent↗

Restless legs syndrome and sleep disturbance during pregnancy: the role of folate and iron.

Restless legs syndrome (RLS) is a neurosensory disorder that typically begins in the evening and often prevents a person from falling asleep. It has been associated with iron deficiency anemia and dopaminergic pathways and is often treated with iron infusion or dopamine agonists. The purpose of this secondary analysis of longitudinal data collected on women before, during, and after pregnancy is to document the prevalence of RLS during pregnancy, contrast its effect on sleep and mood state, and explore the role of folate and iron in the expression of RLS, specifically during the third trimester when the syndrome is most distressing. The prevalence increased from 0 during preconception to 23% (n = 7) during the third trimester of pregnancy. Only 1 subject continued to experience RLS after delivery. Compared with those without complaints of restless legs, those with restless legs had low serum ferritin at preconception and significantly lower folate levels during preconception and at each trimester. In addition, time to sleep onset was significantly delayed and depressed mood was significantly higher in the RLS group. Rather than indicators of iron deficiency anemia (serum ferritin, serum iron, and hemoglobin) or pernicious anemia (vitamin B(12)), it was reduced serum folate level that was associated with RLS in this sample of pregnant women. Findings indicate a need to reconsider recommendations about the normal ranges of serum ferritin and serum folate levels during pregnancy to minimize the complaints of restless legs and promote more consolidated sleep and better daytime mood state during pregnancy.

Adult↗

The influence of sleep and activity patterns on fatigue in women with HIV/AIDS.

The cause of HIV-related fatigue is most likely multifactorial. When presented as a chief complaint, clinicians often include an assessment of stress level, depression, anemia, infection, and amount of sleep and activity. The empirical bases for these evaluations vary in their validity and implementation in clinical practice, but the basis for evaluating adequate amounts of sleep and activity currently lacks empirical research. The purpose of this study was to describe HIV seropositive women's sleep and activity patterns related to their fatigue experience. Sleep and activity were assessed with wrist actigraphy to obtain objective measures of total sleep time, number of awakenings, and sleep efficiency, as well as level of daytime activity, 24-hour activity rhythm, and naps. This sample of 100 women with HIV/AIDS averaged only 6.5 hours of sleep at night, and 45% of the sample napped. CD4 cell counts were unrelated to sleep and fatigue measures. Compared to the low-fatigue group, the women with high fatigue had significantly more difficulty falling asleep, more awakenings from nighttime sleep, poorer daytime functioning, and a higher frequency of depressive symptoms. Findings from this study provide clinicians with empirically based support for detailed clinical evaluations of sleep and activity patterns, as well as anxiety and depression, in clients who complain of fatigue. Findings also provide data for potential interventions to improve sleep and activity in persons living with HIV/AIDS and to reduce fatigue and depressive symptoms.

Adult↗

Sleep and fatigue.

This chapter provides a review and synthesis of research on women's sleep and fatigue from a nursing perspective. Most of the research involves four primary issues for women: menstrual cycles, childbearing, chronic mental or physical illness, and oncology. Research with healthy women focused on diurnal fluctuations in fatigue and relationships to sleep, without regard for exercise or level of daytime activity. Research on chronic illness and cancer fatigue focused on general fatigue and its impact on activity, without regard for sleep or therapeutic use of rest and naps. A comparison of these two areas highlights gaps in nursing knowledge about sleep and fatigue. Further research is needed to understand relationships between nonrestorative sleep, fatigue, and symptoms related to poor quality of life. From a synthesis of these studies, nonpharmacologic interventions that could be prove useful in promoting a higher quality of life for those with either acute or chronic fatigue are then proposed.

Chronic Disease↗

REM sleep and mood state in childbearing women: sleepy or weepy?

STUDY OBJECTIVES: To test the hypotheses that: 1) an increase in endogenous progesterone levels during the luteal phase of the menstrual cycle will alter REM sleep and mood state, and 2) a decrease in endogenous progesterone levels during postpartum will also alter REM sleep and mood state. DESIGN: A longitudinal descriptive study utilizing ambulatory polysomnography for two consecutive nights at seven time points. SETTING: Subject's homes. PARTICIPANTS: The first hypothesis was tested with 34 women studied during both the follicular and luteal phases of their menstrual cycle. The second hypothesis was tested with 31 women who completed the sleep studies during pregnancy and at one month postpartum. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Women who ovulated (high levels of serum progesterone in the luteal phase) had shorter REM latency, more REM sleep, and more positive mood state compared to those who did not ovulate (low luteal progesterone). Compared to the third trimester (high progesterone), REM latency was significantly shorter at one month postpartum (low progesterone). Mood state was most positive at the second trimester and most negative at one month postpartum. CONCLUSIONS: REM sleep and mood state were related to low progesterone levels during the menstrual cycle, but postpartum REM sleep and mood state were related to increased wake time rather than changes in progesterone levels.

Adult↗

Transcriptional activation by the Ewing's sarcoma (EWS) oncogene can be cis-repressed by the EWS RNA-binding domain.

The Ewing's sarcoma (EWS) oncogene contains an N-terminal transcriptional activation domain (EWS activation domain, EAD) and a C-terminal RNA-binding domain (RBD). Although it has been established that the EAD is a potent trans-activation domain that is required for the oncogenic activity of several EWS fusion proteins (EFPs), the precise function of the RBD and the normal role of intact EWS are poorly characterized. Here we show that a cis-linked RBD can strongly and specifically repress trans-activation by the EAD. Fusion proteins containing the RBD are expressed at normal levels, are nuclear-localized, and can bind to DNA both in vitro and in vivo, demonstrating that the RBD represses trans-activation directly at the promoter. The RNA recognition motif within the RBD is not required for repression, whereas regions of the RBD containing multiple RGG motifs play a critical role. The finding that the RBD can antagonize transcriptional activation by EWS provides the first direct evidence of a role for the RBD in transcription. Further studies of the repression phenomenon should illuminate key molecular interactions that distinguish EWS from EFPs and provide insights into the normal cellular function of EWS.

Cell Line↗

Phospholipase D1 is phosphorylated and activated by protein kinase C in caveolin-enriched microdomains within the plasma membrane.

Activities of phospholipase D (PLD) in diverse subcellular organelles have been identified but the details of regulatory mechanisms in such locations are unknown. Protein kinase C (PKC) is a major regulator of PLD. Serine 2, threonine 147, and serine 561 residues of phospholipase D1 (PLD1) were determined as sites of phosphorylation by PKC (Kim, Y., Han, J. M., Park, J. B., Lee, S. D., Oh, Y. S., Chung, C., Lee, T. G., Kim, J. H., Park, S. K., Yoo, J. S., Suh, P. G., Ryu, S. H. (1999) Biochemistry 38, 10344-10351). In our present study, a triple mutation of these phosphorylation sites diminished markedly phorbol 12-myristate 13-acetate (PMA)-induced PLD1 activity in COS-7 cells. We looked at the location of the PLD1 phosphorylation by PKC by observing PMA induced band shifts and by use of anti-phospho-PLD1 monoclonal antibody. The shifted PMA-induced proteins and the immunoreactivity of the anti-phospho-PLD1 antibody were mainly found in the caveolin-enriched membrane (CEM) fraction. Depletion of cellular cholesterol led to a loss of this compartmentalization of phosphorylated PLD1 in the CEM. Replacement of the cellular cholesterol led to the restoration of phosphorylated PLD1 in the CEM. Immunocytochemical studies of COS-7 cells revealed that PLD1 was localized in the plasma membrane as well as in the vesicular structures in the cytoplasm, but the phosphorylation of PLD1 occurred only in the plasma membrane. Our results, therefore, show that phosphorylation, and thereby activation, of PLD1 by PKC occurs in the caveolin and cholesterol-enriched low density domain of the plasma membrane in COS-7 cells.

Animals↗

Acculturation and perinatal health outcomes among rural women of Mexican descent.

Research has shown that health outcomes for urban women of Mexican descent are related to acculturation. The purpose of this research was to compare perinatal outcomes of 773 women of Mexican descent who gave birth in three rural northern California hospitals, in relation to acculturation measured three different ways: by place of birth, by language spoken, and by the two factors combined as an Acculturation Index (AI). The prenatal and birth records of 773 Mexico-born or U.S.-born women of Mexican descent were reviewed. Results showed that language spoken was a less useful indicator of acculturation associated with perinatal complications than place of birth or the AI. The categorization of acculturation with the AI enhanced understanding of more specific groups of rural women and their particular health outcomes.

Acculturation↗

Parity and sleep patterns during and after pregnancy.

OBJECTIVE: To describe changes in women's sleep patterns from prepregnancy to postpartum. METHODS: Polysomnography was done in women's homes for 2 consecutive nights. Forty-five women were studied during the follicular and luteal phases of their menstrual cycles, and 33 conceived and were studied during each trimester of pregnancy. Twenty-nine were studied at 1 and 3 months postpartum. RESULTS: Compared with prepregnant sleep characteristics, significant changes in sleep patterns were evident by 11-12 weeks' gestation, with a significant increase in total sleep time but less deep sleep and more awakening during sleep. By the third month postpartum, there was improvement in sleep characteristics; however, sleep efficiency remained significantly lower than baseline prepregnancy values. CONCLUSION: Sleep disturbance was greatest during the first postpartum month, particularly for first-time mothers.

Adult↗