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Biomedical subjects

K Leung

Publications and source records attributed to K Leung.

At least 73 records · Page 4Linked to original sources

Sympathy and support for industrial actions: a justice analysis.

The authors investigated the effects of different causes of grievance and different types of industrial action on observers' justice perceptions and their sympathy toward and support for grievants in industrial actions. Results indicated that grievances based on interactional injustice generated a stronger perception of unfairness, more sympathy, and more support than did grievances based on procedural injustice, which in turn generated a stronger perception of unfairness, more sympathy, and more support than did grievances based on distributive injustice. Ss also expressed less support for strikes than for sit-ins, but no such difference because of the types of industrial action taken was found for perceived fairness and sympathy. Finally, the ratings on perceived fairness, sympathy, and support were more discrepant among the three types of grievance for sit-ins than for strikes.

Adult↗

Tumor necrosis factor receptor expression and signal transduction in HIV-1-infected cells.

OBJECTIVE: To examine the inter-relationship between HIV-1 infection and the cell surface receptors for tumor necrosis factor (TNF)-alpha, an immunoregulatory cytokine that can enhance HIV-1 replication. DESIGN: Infected promyelocytic and promonocytic cells were examined because they normally express both types of TNF receptors. METHODS: TNF receptor surface expression was determined by specific monoclonal antibody recognition and flow cytometry, and signal transduction was detected by gel shift analysis. HIV-1 activation and expression was quantitated by reverse transcriptase assay. RESULTS: In the OM-10.1 promyelocytic model of chronic infection, TNF-alpha-induced HIV-1 expression also resulted in a substantial increase in 75 kd TNF receptor (TR75) expression although 55 kD TNF receptor (TR55) levels were not dramatically altered. A series of uninfected parental HL-60 subclones all reduced TR75 surface expression in response to TNF-alpha treatment. Enhanced TR75 expression on OM-10.1 cells followed the same TNF-alpha-dose dependency as that observed for HIV-1 production. An increase in TR75 expression was also evident during the peak of an acute HIV-1 infection of HL-60 promyelocytes. Although TR55 expression was unaltered during TNF-alpha-induced HIV activation, this receptor was still involved in the viral activation process. Antibody cross-linking of TR55, in the absence of exogenous TNF-alpha, induced maximal HIV-1 expression, an up-modulation of surface TR75, and nuclear NF-kappa B activity in OM-10.1 cultures. Surprisingly, this was the case even when an antagonistic anti-TR55 antibody was used. Anti-TR55 antibody cross-linking in chronically infected U1 promonocytic cultures could only partially substitute for TNF-alpha-induced HIV-1 expression. CONCLUSIONS: Our results demonstrated that HIV-1 infection can selectively influence the surface expression of TNF receptors, potentially influencing its own expression and altering normal immunoregulatory signal transduction.

Cells, Cultured↗

Differential regulation of vascular cell adhesion molecule 1 gene expression by specific NF-kappa B subunits in endothelial and epithelial cells.

Vascular cell adhesion molecule 1 (VCAM-1) is expressed in both endothelial and epithelial cell types, where it contributes to lymphocyte migration to sites of inflammation. Its expression is regulated by cytokines, in part through two kappa B-like regulatory elements. Because NF-kappa B can be composed of multiple alternative subunits with differential effects on gene expression, the role of different specific NF-kappa B family members subunits in VCAM-1 regulation is unknown. In this report, we define the contribution of different NF-kappa B family members to VCAM-1 gene regulation. We show that both kappa B sites in the VCAM-1 enhancer are required to optimally stimulate gene expression, but the enhancer is differentially regulated by specific combinations of NF-kappa B subunits. At low concentrations, RelA(p65) acted in concert with the approximately 50-kDa product of p105 NF-kappa B, NF-kappa B1(p50), to stimulate transcription, and at high concentrations, RelA(p65) alone stimulated the VCAM-1 promoter. In contrast, NF-kappa B2 inhibited functional activation of the VCAM reporter by p65. Consistent with this finding, an additional binding complex was detected by using recombinant NF-kappa B2(p49)/RelA(p65) with radiolabeled VCAM kappa B site probes. Interestingly, the human immunodeficiency virus enhancer responded differently to stimulation by NF-kappa B subunits, with optimal response to p49(100)/p65. Analysis of NF-kappa B mRNA in human umbilical vein endothelial cells revealed that nfkb1, nfkb2, and relA NF-kappa B but not c-rel were induced by tumor necrosis factor alpha and lipopolysaccharide, which also induce VCAM-1. These data suggest that specific subunits of NF-kappa B regulate VCAM-1 and differentially activate other genes in these cells.

Animals↗

A quantitative method for classification of EEG in the fetal baboon.

Electroencephalographic (EEG) activity is used as a primary indicator of sleep states in adults and infants of many species and in the ovine fetus. We recently reported that the baboon fetus exhibits visually discernable patterns of EEG activity. One pattern of activity, characterized by the intermittent presence of repetitive bursts of high-voltage EEG, is indistinguishable from trace alternant (TA). TA is a distinctive pattern of EEG activity found only during early stages of development in primates. TA is the predominant pattern of EEG activity during quiet sleep in human infants < 2 mo of age. The focus of this study was to derive quantitative parameters that would discriminate TA from other activity and then to develop a method for automated categorization of EEG patterns. Results demonstrate that several parameters derived from frequency-domain analyses are related to visually coded EEG states. Among these parameters, high-frequency power (12-24 Hz) and spectral-edge frequency are good discriminators of EEG patterns. This paper describes a new parameter, EEG ratio, computed as spectral power in the rectified EEG within a band that corresponds to the frequency of bursts of activity during TA (0.03-0.20 Hz) divided by power in the 12- to 24-Hz band. This new composite parameter of EEG activity provides a markedly better correlate of visually coded EEG than any of the individual parameters tested. Using cluster analysis, we devised a method for objective minute-by-minute dichotomization of EEG ratio. The method produces results that agree with visual coding of EEG activity 87.1% of the time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Distinct combinations of NF-kappa B subunits determine the specificity of transcriptional activation.

The nuclear factor that binds to the kappa light-chain enhancer of B cells (NF-kappa B) is a transcription factor that regulates the expression of a variety of cellular and viral genes. NF-kappa B is composed of distinct subunits, and at least four independent genes (p105, p100, p65, and c-rel) have been isolated that encode related proteins that bind kappa B sites. Because it is possible that specific interactions of different subunits can allow selective gene activation, we have characterized the specificity of transcriptional activation by various combinations of these subunits. When tested alone, an approximately 49-kDa form (p49) of the p100 protein bound weakly to kappa B, but p49 associated with p65 to bind efficiently to this site. Furthermore, p49 acted in combination with either p65 or a Rel/VP16 fusion protein to activate kappa B-dependent transcription in Jurkat T leukemia cells. The p49/p65 or p49/Rel combination stimulated transcription mediated by the canonical kappa B site but did not stimulate reporter genes containing interleukin 2 receptor alpha or major histocompatibility complex kappa B elements, despite its ability to bind to these sites. Transactivation mediated by the p49/p100 and p65 NF-kappa B proteins is therefore sensitive to minor changes in the sequence of the kappa B site. Specificity determined by the association of NF-kappa B subunits provides a mechanism to selectively regulate variant kappa B sites associated with different cellular and viral genes.

Base Sequence↗

Localization of the gene encoding R kappa B (NFRKB), a tissue-specific DNA binding protein, to chromosome 11q24-q25.

Although NF (nuclear factor)-kappa B binds in vitro to several of the kappa B regulatory elements found in cellular and viral genes, another DNA binding protein, R kappa B, also binds to a related variant of the kappa B site that regulates interleukin-2 receptor alpha-chain gene expression, a critical event in T cell activation. Southern blot analysis of a human-mouse somatic cell hybrid panel and in situ hybridization using a fluorescent genomic R kappa B probe have allowed assignment of the R kappa B gene (NFRKB) to 11q24-q25. The NFRKB locus is in close proximity to the chromosomal breakpoint implicated in Ewing sarcoma, but it does not appear to span this region. Nonetheless, NFRKB may be particularly useful as the most telomeric marker thus far assigned to 11q.

Animals↗

Relations with parents and school and Chinese adolescents' self-concept, delinquency, and academic performance.

Current research and theory have suggested that the relational domains of family and school experiences are important to children's development. The present study thus examined how relations with parents and school were related to Chinese students' psychosocial and cognitive development in self-concept, delinquency, and academic performance. A total of 1668 secondary school students were studied, and results showed that better relation with parents was associated with higher general, academic, appearance, social, and physical ability self-concepts. Better relation with school was associated with higher academic performance, as shown in higher class rank, higher grand total exam scores, and higher scores in Chinese, English, mathematics, physical education, and music. Both poorer relations with parents and school were found to associate with more self-reported delinquency as well as more school records of misconduct.

Achievement↗

Bioavailability improvement of mycophenolic acid through amino ester derivatization.

The potential bioavailability improvement of mycophenolic acid (MPA), 1, through ester derivatization was evaluated in monkeys at a dose of 20 mg/kg in this study. The acetyl solketal ester 3 was found to have excellent partition properties but poor aqueous solubility. Thus, even though it can be converted rapidly to MPA by plasma and liver enzymes, it showed poor oral bioavailability (56% of MPA) in monkeys. The bioavailability of the morpholinoethyl ester 4 and the acetyl morpholinoethyl ester 5, on the other hand, was found to be 236 and 150% that of MPA, respectively. Since ester 5 has greater aqueous solubility, but similar chemical stability and enzymatic hydrolysis rates compared to ester 4, the better bioavailability of ester 4 may result from its greater partitioning into the gastrointestinal membranes.

Administration, Oral↗

Mechanism of regulating human leukemia cell growth and differentiation by a lymphokine.

Human myelogenous leukemia cells can be induced to differentiate in vitro along the monocyte-macrophage pathway by a T cell lymphokine maturation inducer. Maturation inducer has now been purified from a human T cell line and determined to be a single chain protein with an approximate molecular weight of 53,500. It induces the differentiation and proliferation of human leukemic HL-60 promyelocytes in a dosage-dependent fashion. Initial interaction with cells at G1 phase induced the cells to enter proliferating S phase. Subsequent differentiation from S phase was dependent on an optimal inducer quantity (18.7 pM - 18.7 nM) which mediated growth cessation and termination differentiation to monocytes-macrophages. When inducer quantity was more or less than this optimal range, the cells did not undergo differentiation but were continuously stimulated to proliferate. This may represent an important proliferation mechanism of leukemic cells.

Cell Cycle↗

Activation of HIV gene expression during monocyte differentiation by induction of NF-kappa B.

The latent period of AIDS is influenced by factors which activate human immunodeficiency virus (HIV) replication in different cell types. Although monocytic cells may provide a reservoir for virus production in vivo, their regulation of HIV transcription has not been defined. We now report that HIV gene expression in the monocyte lineage is regulated by NF-kappa B, the same transcription factor known to stimulate the HIV enhancer in activated T cells; however, control of NF-kappa B and HIV in monocytes differs from that observed in T cells. NF-kappa B-binding activity appears during the transition from promonocyte to monocyte in U937 cells induced to differentiate in vitro and is present constitutively in mature monocytes and macrophages. In a chronically infected promonocytic cell, U1, differentiation is associated with HIV-1 replication as well as NF-kappa B binding activity. These findings suggest that NF-kappa B binding activity is developmentally regulated in the monocyte lineage, and that it provides one signal for HIV activation in these cells.

Cell Differentiation↗

Production and response to an autologous growth factor isolated from human leukemia cells.

Human myeloid leukemia HL-60 cells have been shown to release into culture medium an activity that promotes the proliferation of these same HL-60 cells. The presence of additional culture supernatant containing growth-promoter activity accelerates the HL-60 growth rate as determined by cell counts and [3H]thymidine uptake. Isolation of this growth promoter has been performed with the serum-free supernatant of HL-60 cells using salt precipitation, DEAE-Sepharose ion exchange chromatography, and gel electrophoresis. The promoter activity was recovered from SDS-gel electrophoresis within the 60- to 85-kDa mol wt range where a single band of an apparent mol wt of 72,000 was demonstrated. The ability of HL-60 cells to respond to the growth promoter was significantly lost 4 h after exposure to differentiation-inducing activity, while production of the growth promoter was diminished only after 2-3 days following induction of differentiation. These results suggest that the growth-promoting mechanism is associated with the undifferentiated leukemic state. In addition, the role of an autocrine growth mechanism in maintaining the leukemic cells in an undifferentiated state is discussed.

Cell Differentiation↗

High performance liquid chromatography of steroids in bovine adrenal glands: changes during the postpartum interval.

High performance liquid chromatography was utilized to characterize changes in the content of various steroids in adrenal glands with time postpartum. Adrenal glands were obtained from 32 beef cows on either days, 7, 14, 28, 42 or 56 after parturition (n = 6-8/group). Of the major glucocorticoids, only cortisone significantly changed with time postpartum. Adrenal content of cortisone was 56% lower (P less than 0.05) on day 14 than on days 7, 28, 42 and 56. Average adrenal content (microgram/g) of cortisol, cortisone, corticosterone and 11-dehydrocorticosterone was 3.3, 2.4, 1.8 and 1.8, respectively. All other adrenal steroids measured were less than 0.8 micrograms/g. Correlation coefficients among the adrenal steroids measured indicated that terminal products (e.g. 11-dehydrocorticosterone and cortisone) of glucocorticoidogenesis were positively correlated (r = 0.56-0.64) with each other (P less than 0.05), whereas cortisone was negatively correlated (P less than 0.05) with both 17 alpha-hydroxyprogesterone (r = -0.49) and progesterone (r = -0.58). The latter suggests that a product (cortisone) inhibition mechanism may exist in bovine adrenal glucocorticoidogenesis. Collectively, these data suggest that cortisone should be considered a potential factor in the regulation of physiologic functions in postpartum cattle.

Adrenal Glands↗

Phase I trial of mitomycin C immunoconjugates cocktails in human malignancies.

Nineteen patients with refractory solid malignancies received individualized combinations of mitomycin C conjugated murine monoclonal antibodies selected by immunohistochemical and flow cytometric screening of tumor specimens. There were no responses in this Phase I study. Thrombocytopenia precluded escalation above a mitomycin C dose of 60 mg per treatment cycle. Preclinical, clinical, and toxicity experiences with this investigational approach to the treatment of cancer are discussed.

Adult↗

Immunoconjugates of doxorubicin and murine antihuman breast carcinoma monoclonal antibodies prepared via an N-hydroxysuccinimide active ester intermediate of cis-aconityl-doxorubicin: preparation and in vitro cytotoxicity.

Doxorubicin (DXR) conjugated to murine monoclonal antibodies (MoAb) raised against human breast tumor cells demonstrated a MoAb-specific, molar ratio-dependent in vitro cytotoxicity. These conjugates were prepared on a scale sufficient to allow for subsequent clinical trials (1 to 3 g of MoAb per conjugation reaction). The conjugation reaction proceeded via an N-hydroxysuccinimide (NHS) active ester intermediate of cis-aconityl-DXR (CA-DXR), resulting in a cis-aconitate acid-sensitive linker between the DXR and MoAb. Molar ratios of DXR to MoAb ranged from 40 to 45. The immunoreactivity of conjugated MoAb was only slightly decreased from naked MoAb. When immunoconjugates were incubated with MoAb-reactive tumor cells for 3 hours, specific cell-killing was observed. If the exposure time was lengthened to 18 hours, however, nonspecific killing resulted. Incubation of the immunoconjugate with the nonspecific adsorbant Amberlite XAD-2 caused an average 30% decrease in the DXR-to-MoAb molar ratio, suggesting a population of drug that is tightly but noncovalently associated with MoAb.

Adsorption↗