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Biomedical subjects

H H Kuo

Publications and source records attributed to H H Kuo.

12 recordsLinked to original sources

Epstein-barr virus nuclear antigen 2 retards cell growth, induces p21(WAF1) expression, and modulates p53 activity post-translationally.

The Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) has been shown to be required for promotion of cell-cycle progression in EBV-immortalized B-lymphocytes. However, other studies have indicated that EBNA2 alone, in the absence of other EBV genes, may retard cell growth. To resolve this discrepancy, we investigated the effect of EBNA2 on the growth of various cells, including EBV target nasopharyngeal carcinoma cells, NPC-TW01 and NPC-TW04. We found that EBNA2 could retard cell growth, in stable Vero, HEp-2, and U2OS cell clones expressing EBNA2, and in Vero, 293, NPC-TW01, and NPC-TW04 cells transiently transfected with EBNA2. While investigating the mechanism underlying the growth-retarding function of EBNA2, we found that EBNA2 induced p21(WAF1) expression in these cells. This induction of p21(WAF1) expression was mediated through p53. EBNA2 was found to stimulate p53 to bind to the p53-response element within the p21(WAF1) promoter, possibly by promoting p53 phosphorylation. This enhancement of p53 sequence-specific DNA-binding activity may be the mechanism through which EBNA2 activates the expression of p53-regulated genes, including p21(WAF1) and mdm-2. Together, these studies reveal a possible intrinsic function of EBNA2 in cell-growth regulation and elucidate a novel mechanism by which EBNA2 modulates transcription.

Animals↗

Use of the transurethral prostatectomy clinical path to monitor health outcomes.

PURPOSE: We evaluated the effect on cost and medical care quality of use of the transurethral prostatectomy clinical path. MATERIALS AND METHODS: Results in 100 patients treated when the transurethral prostatectomy clinical path was used were compared to those of 100 treated by the same physicians before implementation of this path. RESULTS: After implementation of the transurethral prostatectomy clinical path the length of hospital stay was significantly decreased from 5.9 to 5.0 days (p < 0.01) and Foley catheterization time was significantly decreased from 3.13 to 2.84 days (p < 0.01). Antibiotics were routinely used from the day before surgery to the day of hospital discharge as required by patient conditions. Therefore, a shorter hospital stay will significantly decrease the use of antibiotics. After implementation of the clinical path the average admission charges were decreased significantly by 17% (p < 0.01). Although some results from use of this path will not significantly affect costs, they will reflect some quality improvement. The effect of clinical path implementation on length of hospital stay between patients treated by junior and senior attending physicians was not significant. However, there was a statistically significant difference (p < 0.01) between results obtained by junior and senior attending physicians regarding average admission charges. CONCLUSIONS: Implementation of the transurethral prostatectomy clinical path can improve health care outcome by decreasing length of stay and admission charges, and improving quality of medical care, particularly for patients treated by junior attending physicians.

Aged↗

Complex marital histories and economic well-being: the continuing legacy of divorce and widowhood as the HRS cohort approaches retirement.

We use data from the first wave of the Health and Retirement Survey (HRS) to examine the marital histories of this cohort of women and men on the verge of retirement. The legacy of past increases in divorce rates is evident in the complex marital histories of HRS households and the relationship between those histories and current economic status. Couples in a first marriage now make up only one-quarter of black households and fewer than half of all white and Hispanic households. In over one-third of all married-couple households, at least one spouse had a previous marriage that ended in divorce or widowhood. These couples have significantly lower incomes and assets than couples in first marriages. Contrary to the popular notion that private and public insurance better provide for the security of widows than divorced persons, currently widowed households and couples in which the prior marriage of one spouse had ended in widowhood are no better off than are their divorced peers. This holds true for both black and white households. From a single cross-section, one cannot tell what caused these differences in income and wealth across marital status groups although it is clear that women and blacks spend a higher percentage of their lifetime outside of marriage than do men and whites. We also speculate from estimates of widowhood expectations for a subset of married respondents that underestimating the chances of widowhood--because both men and women overestimate their chances of joint survival--may be a factor in the relatively low economic status of widows. Because couples in life-long marriages have been the traditional standard upon which marital property reform and the survivorship rules of private and public programs are based, their diminishing importance among all households raises concern about the protection provided by these institutions against the long-term economic consequences of past and future marital dissolution.

Cross-Sectional Studies↗

Preeclampsia in multiple pregnancy.

BACKGROUND: Preeclampsia is one of the most common pregnancy-induced complications, and results in a large number of maternal deaths. How pregnancy incites or aggravates hypertension remains unresolved; despite decades of intensive research directed to hypertensive disorders, they remain among the most important unresolved problems in obstetrics. The incidence of preeclampsia is increased in multiple pregnancies, and several preeclampsia-related fetal risks may be particularly hazardous to the babies of multiple gestations. METHODS: The records of 561 women with multiple pregnancies delivered consecutively at Mackay Memorial Hospital were reviewed retrospectively. Thirteen mild cases and 39 severe cases of preeclampsia in multiple pregnancies were compared with 52 control cases of multiple pregnancies without preeclampsia, but matched for maternal age and parity. The categories for comparison included parity, gestational age, time of onset of preeclampsia, route of delivery, mean birth weight, growth discordancy, maternal complications, neonatal morbidity and mortality. RESULTS: The incidence of preeclampsia in our consecutive series of 561 multiple pregnancies was 9.3% compared with 1.8% in singleton pregnancies (p < 0.0001). In primiparas with multiple pregnancies, the incidence of preeclampsia was 12.2% compared with 6.2% (p < 0.05) in multiparas. Breech presentation was the most common indication for Cesarean section in all groups. The preeclamptic group had a significantly higher rate of Cesarean section compared with the control group (p < 0.006), with prolonged labor and fetal distress were the two main reasons for this difference. Severe preeclamptic patients had babies with significantly lower mean birth weights (p < 0.05), higher incidence of intrauterine growth retardation (p < 0.025) and neonatal respiratory distress syndrome (p < 0.0008) compared with those of the control group. All seven cases with maternal complications were in the severe preeclamptic group. CONCLUSIONS: An unfavorable perinatal outcome was found to be associated with severe, but not with mild, preeclampsia in multiple pregnancies.

Female↗

Determination of free progesterone in an ultrafiltrate of saliva collected in situ.

We have investigated the utility of an ultrafiltrate of saliva for measuring progesterone as an indicator of luteal function during the menstrual cycle of women. A filtrate of saliva is collected in the mouth by means of an osmotic pump that accumulates medium containing only molecules less than 12,000 Da. We analyzed the nonextracted ultrafiltrate by a solid-phase immunoassay for progesterone and monitored the mid-luteal surge of lutropin in urine with a liquid-phase radioimmunoassay. Progesterone concentrations in the ultrafiltrate are significantly lower during the follicular phase and increase after the release of lutropin. The concentration of progesterone in the ultrafiltrate correlates closely with total progesterone in matched blood samples (r = 0.84, cycle 1; and r = 0.89, cycle 2). Likewise, we found a good correlation between the results in whole saliva and in the ultrafiltrate (r = 0.95). The described method of obtaining a pre-processed specimen noninvasively simplifies the self-collection of samples by patients (including collection at home); excludes potential interference from microorganisms, desquamated cells, and salivary components; and simplifies the processing of the biological fluid in the laboratory.

Adult↗

Interferon-mediated inhibition of prostaglandin synthesis in human mononuclear leukocytes.

In this study, the question of whether human leukocyte-derived and fibroblast-derived interferon had an effect on prostaglandin metabolism in human peripheral blood mononuclear cells has been considered. Both leukocyte- and fibroblast-derived interferon were potent inhibitors of mononuclear cell prostaglandin synthesis at low physiological concentrations. Inhibition required a minimum incubation of 1 hr. Interferon had no effect on release of arachidonic acid; synthesis of hydroxy fatty acids was slightly increased.

Arachidonic Acid↗

Influence of azathioprine (imuran) on in vitro immune function in multiple sclerosis.

In vitro immune function was assessed in patients with multiple sclerosis (MS) who were receiving Imuran therapy, in untreated MS patients, and in controls. In untreated stable MS patients, concanavalin A (Con A)-driven mitogenic reactivity (T effector function) and Con A-induced suppressor activity were modestly reduced compared to controls; pokeweed mitogen-induced immunoglobulin G (IgG) secretion was increased. Untreated patients with active MS demonstrated high levels of IgG secretion and marked decreases in suppressor activity. In Imuran-treated patients, Con A mitogenic responses and suppressor activity were comparable to those observed in untreated stable patients, and IgG secretion was reduced. The results in the treated patients likely reflect a direct effect of Imuran on B cell function rather than an indirect effect mediated via suppressor cells.

Adolescent↗

Modulation of T-lymphocyte differentiation antigens: potential relevance for multiple sclerosis.

Effects of the anti-T-cell monoclonal antibodies OKT3, OKT5, and OKT8 on T-cell surface properties and cell functions were evaluated. Incubation of mononuclear cells isolated from peripheral blood for 48 hr with each monoclonal antibody in the absence of complement resulted in modulation of their respective surface antigens; i.e., the number of cells detected by immunofluorescence as positive for the T3, T5, and T8 surface antigens was reduced. T3, T5, and T8 antigens modulated independently. A radiolabeled second antibody technique confirmed modulation by OKT3 and OKT8 and indicated that T-cell differentiation antigens can regenerate in culture. Incubation of mononuclear cells with OKT3 increased the number of sheep erythrocyte-binding lymphocytes (E+-rosetting cells) and markedly increased the number of avidly E+-rosetting cells. Incubation with OKT8 reduced the number of E+- and of avidly E+-rosetting cells. OKT3 induced both mitogenic reactivity and suppressor cell activity; cells modulated by OKT8 exhibited reduced mitogenic reactivity and reduced suppressor cell function. The decreases in total T cells, in avid T cells, in suppressor cell number, and in suppressor cell function that follow modulation by OKT8 mimic changes observed in multiple sclerosis patients.

Adult↗

Generation of suppressor cells by aggregated human globulin.

We have studied the capacity of aggregated human globulin, a model for immune complexes, to induce suppressor cells which modulate a predominantly T cell response, i.e. the proliferative response of autologous mononuclear cells to concanavalin A. We utilized a soluble aggregated human globulin preparation depleted of both high molecular weight (greater than 4 x 10(6) daltons) insoluble aggregates and monomeric IgG. The mean per cent suppression induced by mononuclear cells preincubated with aggregated human globulin for 96 hr was 39 +/- 8%; monomeric IgG did not induce significant suppression (4 +/- 6%). We found a close correlation between the magnitude of suppression induced by preincubation for 96 hr with aggregated human globulin and that induced by preincubation with concanavalin A. Kinetic analysis indicated that suppressor cell induction by aggregated human globulin required 48 hr of preincubation; suppressor cell induction by concanavalin A required 24 hr. Aggregated human globulin-induced suppression was not associated with DNA synthesis as measured by 3H-thymidine uptake. The findings suggest that immune complexes can modulate immunoregulation.

Adult↗

A new solid-phase radioimmunoassay to measure IgG secreted by cultured human lymphocytes.

We describe a simple solid-phase radioimmunoassay (RIA) to detect IgG based on competitive binding between radiolabeled and unlabeled IgG for anti-IgG antibody physically adsorbed to the wells of polyvinyl microtiter plates. The assay is sensitive (1 ng), rapid, and is particularly suited for studies of in vitro IgG secretion by human peripheral blood lymphocytes, since such studies require large numbers of cultures. Conditions which permit measurement, by means of this assay, of helper and suppressor T cell effects on IgG production by human B cells in culture are described.

Animals↗

Gender, family configuration, and the effect of family background on educational attainment.

A comprehensive model of family influences on educational resemblance of siblings expands the traditional sibling pair model to a full sibship model in order to investigate how gender, gender composition of sibships, and a measure of ordinal position moderate the effect of social origins on educational attainments of siblings. One common family factor is sufficient to explain the variation of educational attainment among brothers and sisters. Although effects of social origins variables on brothers are larger than on sisters, the relative effects of measured social origins are virtually the same among sisters and brothers. The disparity between educational attainments of brothers and sisters persists across sex composition and family size. Ordinal position does not alter the effects of social origins on educational attainment nor does it directly affect educational attainment. Father's and mother's education are equally important for all siblings regardless of birth order, gender composition, and family size.

Adolescent↗