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Biomedical subjects

J Yang

Publications and source records attributed to J Yang.

At least 487 records · Page 27Linked to original sources
PubMed2000

Signaling and transcription in T helper development.

The recognition of polarized T cell subsets defined by cytokine production was followed by a search to define the factors controlling this phenomenon. Suitable in vitro systems allowed the development of cytokine "recipes" that induced rapid polarization of naïve T cells into Th1 or Th2 populations. The next phase of work over the past several years has begun to define the intracellular processes set into motion during Th1/Th2 development, particularly by the strongly polarizing cytokines IL-12 and IL-4. Although somewhat incomplete, what has emerged is a richly detailed tapestry of signaling and transcription, controlling an important T cell developmental switch. In addition several new mediators of control have emerged, including IL-18, the intriguing Th2-selective T1/ST2 product, and heterogeneity in dendritic cells capable of directing cytokine-independent Th development.

Animals↗
PubMed2000

Pranidipine enhances the action of nitric oxide released from endothelial cells.

Nitric oxide (NO) synthesis in vascular endothelium of patients with hypertension is altered. Calcium antagonists have been shown to improve endothelial function in hypertensive patients. Here we report that pranidipine, one of the latest long-acting calcium antagonists in the dihydropyridine group, enhances the actions of NO released from endothelial cells (ECs). Pranidipine significantly enhanced cGMP accumulation in vascular smooth muscle cells cocultured with ECs, whereas amlodipine and nifedipine had no significant effects. In addition, pranidipine also suppressed basal and thrombin-stimulated endothelin-1 production from ECs. Pranidipine also enhanced cGMP accumulation in rat aortic segments with endothelium but not in endothelium-denuded vessels. In contrast, pranidipine had no effect in the presence of N(G)-monomethyl-L-arginine, an inhibitor of NO synthesis. Pranidipine did not affect the basal expression of endothelial NO synthase in ECs. However, pranidipine upregulated the activity of superoxide dismutase in ECs. These findings suggest that pranidipine enhances NO action through inhibition of superoxide-induced NO decomposition in the vessel wall. Thus, pranidipine may be useful in the treatment of impaired endothelial function in patients with hypertension.

Amlodipine↗
PubMed2000

Familial aggregation of bronchodilator response: a community-based study.

We investigated familial aggregation of bronchodilator response (BDR) among 4,946 subjects selected from 1,161 index families with asthma in a rural community in China. Each family unit consisted of both parents and their first and subsequent offspring, aged 8-20. Raw BDR measurements, defined as the percentage change in FEV(1) after 180 microg of albuterol, were adjusted to account for sex, age, height, weight, education, smoking, asthma, wheeze, and allergy status. Using these adjusted BDR values, we found significant correlation for father-first offspring pairs, mother-first offspring pairs, mother-subsequent offspring pairs, and first offspring-subsequent offspring pairs. The overall magnitude of the correlation coefficient (0.088-0.165) suggests a modest degree of familial clustering. The largest odds ratio was seen for subsequent offspring who had mothers and first offspring with adjusted BDR values above the median: 3.10 (95% CI: 1.85-5.20) in these index families with asthma. Thus, our data support a significant familial aggregation of BDR in this Chinese population, which points to a role of genetic factors in BDR.

Administration, Inhalation↗
PubMed2000

Endosomal processing limits gene transfer to polarized airway epithelia by adeno-associated virus.

The restriction of viral receptors and coreceptors to the basolateral surface of airway epithelial cells has been blamed for the inefficient transfer of viral vectors to the apical surface of this tissue. We now report, however, that differentiated human airway epithelia internalize rAAV type-2 virus efficiently from their apical surfaces, despite the absence of known adeno-associated virus-2 (AAV-2) receptors or coreceptors at these sites. The dramatically lower transduction efficiency of rAAV infection from the apical surface of airway cells appears to result instead from differences in endosomal processing and nuclear trafficking of apically or basolaterally internalized virions. AAV capsid proteins are ubiquitinated after endocytosis, and gene transfer can be significantly enhanced by proteasome or ubiquitin ligase inhibitors. Tripeptide proteasome inhibitors increased persistent rAAV gene delivery from the apical surface >200-fold, to a level nearly equivalent to that achieved with basolateral infection. In vivo application of proteasome inhibitor in mouse lung augmented rAAV gene transfer from undetectable levels to a mean of 10.4 +/- 1.6% of the epithelial cells in large bronchioles. Proteasome inhibitors also increased rAAV-2-mediated gene transfer to the liver tenfold, but they did not affect transduction of skeletal or cardiac muscle. These findings suggest that tissue-specific ubiquitination of viral capsid proteins interferes with rAAV-2 transduction and provides new approaches to circumvent this barrier for gene therapy of diseases such as cystic fibrosis.

Animals↗
PubMed2000

Regulation of expression of the multidrug resistance protein MRP1 by p53 in human prostate cancer cells.

The expression of several drug-resistance genes, including MRP and p53, increases with advancing stage of human prostate cancer. Altered transcription could account for the genotypic alterations associated with prostate cancer progression, and it was recently reported that the promoter of MRP1 is activated in the presence of mutant p53. To determine whether there is a relationship between p53 status and the expression of MRP1, a human, temperature-sensitive p53 mutant (tsp Val(138)) was transfected into LNCaP human prostate cancer cells. In the transfected cell line (LVCaP), the wild-type p53 produced growth arrest at the G1/S interface of the cell cycle, inhibited colony formation, and induced p21(waf1/cip1). Temperature shifting to 38 degrees C (p53 mutant) produced a time-dependent increase in expression of MRP1. This change in MRP1 expression was also seen in isogenic cell lines in which p53 was inactivated by human papilloma virus (HPV)16E6 protein or by a dominant-negative mutant. Functional assays revealed a decrease in drug accumulation and drug sensitivity associated with mutant p53 and increased MRP1 expression. These results provide the first mechanistic link between expression of MRP1 and mutation of p53 in human prostate cancer and support recent clinical associations. Furthermore, these data suggest a mechanism tying accumulation of p53 mutations to the multidrug resistance phenotype seen in this disease.

Antineoplastic Agents↗
PubMed2000

Response style and the revised NEO personality inventory: validity scales and spousal ratings in a Chinese psychiatric sample.

The effects of response style bias on profile scores from the family of NEO scales and the resultant influence of response style on the predictive capacity of these scales continues to be debated. In this study, a large sample of Chinese psychiatric patients were categorized into four response style groups based on their scores from recently developed "validity" scales for the revised NEO Personality Inventory (NEO PI-R). Mean differences and correlations between self-report and spousal ratings of these patients were examined for the NEO PI-R domain and facet scales. Excessive positive self-presentation bias resulted in mean differences between the self-report and spousal ratings for N and E. Correlations between self-report and spousal ratings were reduced in patients engaging in positive self-presentational bias compared to those who were not so categorized on three of the five NEO PI-R scales. However, these results were manifest only in a sub-sample of psychotic patients. Negative self-presentational bias did not affect mean differences or diminish the correlations between the self-report and spousal ratings.

Adult↗
PubMed2000

Silent lacunar lesions detected by magnetic resonance imaging of children with brain tumors: a late sequela of therapy.

BACKGROUND: Cerebral lacunes, which generally appear on magnetic resonance imaging as foci of white matter loss, usually occur in adults after ischemic infarcts. We report the development of lacunes in children after therapy for brain tumors. PATIENTS AND METHODS: We reviewed the clinical characteristics and radiologic studies of 524 consecutive children with brain tumors treated over a 10-year period. We documented the neuropsychologic findings associated with lacunes and the factors predictive of lacunar development. RESULTS: Lacunes developed in none of the 103 patients observed or treated with surgery alone. Twenty-five of the 421 patients treated with chemotherapy or radiation therapy or both had lacunes. Patients were a median of 4.5 years old at the time of both diagnosis (range, 0.3 to 19.8 years) and radiotherapy (range, 1.5 to 20 years). Fourteen patients were treated with craniospinal irradiation, and 11 were treated with local radiotherapy. The median time from radiotherapy to the appearance of lacunes was 2.01 years (range, 0.26 to 5.7 years). For all patients, lacunes were an incidental finding with no corresponding clinical deficits. The factor most predictive of lacunar development was age less than 5 years at the time of radiotherapy (P =.010). There was no significant difference in estimated decline in intelligence quotient scores between patients with lacunes and age and diagnosis-matched controls. CONCLUSION: Lacunes may be caused by therapy-induced vasculopathy in children with brain tumors, with the most significant predictor being age less than 5 years at the time of radiotherapy.

Adolescent↗
PubMed2000

MEKK1 activation of human estrogen receptor alpha and stimulation of the agonistic activity of 4-hydroxytamoxifen in endometrial and ovarian cancer cells.

Estrogens are mitogens that stimulate the growth of both normal and transformed epithelial cells of the female reproductive system. The effect of estrogens is mediated through the estrogen receptors, which are ligand-regulated transcription factors. Tamoxifen, a selective estrogen receptor modulator, functions as an estrogen receptor antagonist in breast but an agonist in uterus. In the current study, we show that coexpression of a constitutively active MEKK1, but not RAF or MEKK2, significantly increases the transcriptional activity of the receptor in endometrial and ovarian cancer cells. The expression of wild-type MEKK1 and an active Rac1, which functions upstream of MEKK1, also increased the activity of the receptor while coexpression of dominant negative MEKK1 blocked the Rac1 induction, indicating that endogenous MEKK1 is capable of activating the receptor. Additional experiments demonstrated that the MEKK1-induced activation was mediated through both Jun N-terminal kinases and p38/Hog1 and was independent of the known phosphorylation sites on the receptor. p38, but not Jun N-terminal kinases, efficiently phosphorylated the receptor in immunocomplex kinase assays, suggesting a differential involvement of the two kinases in the receptor activation. More importantly, the expression of the constitutively active MEKK1 increased the agonistic activity of 4-hydroxytamoxifen to a level comparable to that of 17beta-estradiol and fully blocked its antagonistic activity. These findings suggest that the uterine-specific agonistic activity of the tamoxifen compound may be determined by the status of kinases acting downstream of MEKK1.

Endometrial Neoplasms↗
PubMed2000

Moiré technique for spatial coherence measurements of soft-x-ray lasers.

We present a novel moiré diagnostic that allows the time-averaged spatial coherence properties of soft-x-ray lasers to be measured. The technique is an extension of the theoretical work in a recent paper [J. Opt. Soc. Am. A 16, 323 (1999)] and is based on the concept of decompositions of the far-field divergence for partially coherent beams. An appealing feature of the approach is that the spatial coherence width at other planes can be evaluated from the measured one at a given plane on the assumption of shape-invariant beams.

Computer Simulation↗
PubMed2000

Estrogen receptor variants in epithelial compartment of normal human breast.

Estrogen receptor (ER) splice variants have previously been identified in normal human breast. Normal breast, however, comprises many cell types including fat cells, fibroblasts, endothelial cells, and a variety of inflammatory cells besides breast epithelial cells. The objective of our study was to demonstrate the existence of several variants in the epithelial compartment of the normal human breast. To this end, highly enriched breast epithelial cells from reduction mammoplasty specimens were isolated using Percoll gradient centrifugation. We analyzed the presence of both wild-type (WT) and variant receptors in human breast epithelial cells using the seminested polymerase chain reaction and direct automated sequencing of the amplified products. We demonstrated that a number of spliced variants of the ER coexist with the WT receptor. Variants lacking exons 2, 4, 5, and 7 are detected in the breast epithelial compartment of the normal human breast.

Alternative Splicing↗
PubMed2000

The cross-cultural generalizability of Axis-II constructs: an evaluation of two personality disorder assessment instruments in the People's Republic of China.

We examined the reliability, cross-instrument validity, and factor structure of Chinese adaptations of the Personality Diagnostic Questionnaire (PDQ-4+; N = 1,926) and Personality Disorders Interview (PDI-IV; N = 525) in psychiatric patients. Comparisons with data from Western countries suggest that the psychometric properties of these two instruments are comparable across cultures. Low to modest agreement between the PDQ-4+ and PDI-IV was observed for both dimensional and categorical personality disorder evaluations. When the PDI-IV was used as the diagnostic standard, the PDQ-4+ showed higher sensitivity than specificity, and higher negative predictive power than positive predictive power. Factor analyses of both instruments replicated the four-factor structure O'Connor and Dyce (1998) found in Western samples. Results suggested that conceptions and measures of DSM-IV personality disorders are cross-culturally generalizable to Chinese psychiatric populations.

Adult↗
PubMed2000

Use of a novel impermeable biotinylated photolabeling reagent to assess insulin- and hypoxia-stimulated cell surface GLUT4 content in skeletal muscle from type 2 diabetic patients.

Cell surface GLUT4 levels in skeletal muscle from nine type 2 diabetic subjects and nine healthy control subjects have been assessed by a new technique that involves the use of a biotinylated photo-affinity label. A profound impairment in GLUT4 translocation to the skeletal muscle cell surface in response to insulin was observed in type 2 diabetic patients. Levels of insulin-stimulated cell surface GLUT4 above basal in type 2 diabetic patients were only approximately 10% of those observed in healthy subjects. The magnitude of the defect in GLUT4 translocation in type 2 diabetic patients was greater than that observed for glucose transport activity, which was approximately 50% of that in healthy subjects. Reduced GLUT4 translocation is therefore a major contributor to the impaired glucose transport activity in skeletal muscle from type 2 diabetic subjects. When a marked impairment in GLUT4 translocation occurs, the contribution of other transporters to transport activity becomes apparent. In response to hypoxia, marked reductions in skeletal muscle cell surface GLUT4 levels were also observed in type 2 diabetic patients. Therefore, a defect in a common late stage in signal transduction and/or a direct impairment in the GLUT4 translocation process accounts for reduced glucose transport in type 2 diabetic patients.

Biological Transport↗
PubMed2000

The activity of transcription factor Stat5 responds to prolactin, growth hormone, and IGF-I in rat and bovine mammary explant culture.

Signal transducer and activator of transcription-5 (Stat5) is known to play a critical role in prolactin-induced beta-casein gene transcription in rodents. In nonmammary cells, Stat5 is activated by multiple hormones and cytokines, including growth hormone. We hypothesized that Stat5 may serve as a common point in the signal transduction pathways of hormones that promote milk protein gene expression in bovine mammary cells, which are regulated by GH and IGF-I in addition to prolactin. Assays for Stat5 DNA binding activity and protein were validated in mammary explant culture. The Stat5 protein abundance was not changed by any of the short-term hormonal treatments used in our study, suggesting that short-term regulation of Stat5 is predominantly at the level of protein activation. Both rat and bovine explant culture showed a rapid stimulation of Stat5 DNA binding activity by prolactin, GH, and IGF-I at the high concentrations typically used in explant cultures as well as at levels within physiologic ranges. Growth hormone stimulated Stat5 activity at a lower concentration in bovine than in rat cultures, but in both species the presence of GH increased the response of Stat5 activity to prolactin. These results suggest that transcription factor Stat5 may represent part of a common route by which different extracellular signals converge and are transduced intracellularly to coordinately regulate cell function in the mammary gland.

Animals↗
PubMed2000

Physiological levels of Stat5 DNA binding activity and protein in bovine mammary gland.

Signal transducer and activator of transcription (Stat)5 has been implicated in the signal transduction pathways of several factors that are lactogenic or galactopoeitic in mammary cells, including prolactin, GH, and IGF-I. Data from cell or explant culture support the concept that Stat5 may represent part of a common route by which different extracellular signals converge and are transduced into the cell. There are few data on Stat5 activity and level in vivo, and we set out to determine whether physiological stimuli of milk synthesis, including GH, GH-releasing factor, and milking frequency, would be associated with alterations in Stat5 activity or protein. We measured Stat5 DNA binding activity using electrophoretic mobility shift assay and Stat5 protein by Western blot in bovine mammary tissue obtained by biopsy or slaughter. Stat5 activity was absent in nonlactating, nonpregnant cows and was present in late pregnancy and throughout lactation. Stat5 activity varied considerably among cows at similar stages of lactation. Mammary Stat5 activity and protein were determined in hormone-treated lactating cows and mammary quarters of cows milked at different frequencies. Infusion of GH and GH-releasing factor for 2 mo significantly raised levels of milk production and depressed mammary Stat5 activity without influencing Stat5 protein abundance. Mammary Stat5 was also influenced by milking frequency; once-daily milking reduced milk production, Stat5 activity, and protein abundance compared with twice-daily milking. Analysis of mammary Stat5 in relation to milk protein concentration in pooled data from lactating cows indicated that Stat5 activity was correlated (r = 0.505, P < 0.05) with average milk protein concentration and not related to milk protein yield (P > 0.05). These results show that both Stat5 protein and Stat5 activity are modulated by different physiological signals in vivo and suggest that Stat5 lies within in the zone where signal transduction cascades from a variety of factors are convergent. Further work is required to clarify the role of Stat5 in relation to other factors in regulation of milk protein gene expression.

Animals↗
PubMed2000

Telomerase activity in preleukemia and acute myelogenous leukemia.

The development of acute leukemia from preleukemia involves the appearance of clones with increasing proliferative potential. The studies described here demonstrate that telomerase activity progressively increases as the bone marrow cells acquire increasing proliferative potential. This was demonstrated by measuring telomerase activity in normal bone marrow, in post-treatment lymphoma marrows with skewed Lyonization, and in MDS and AML marrows. The greater telomerase activity in myelodysplastic marrow than in normal marrow is not due to a higher proportion of blast cells or to a higher proliferative rate of the MDS marrow. These data demonstrate that the increasing proliferative potential of the marrow which occurs during the development of AML is associated with a simultaneous increase in telomerase activity.

Adolescent↗
PubMed2000

Estrogen receptor variants are present in many normal human tissues.

Estrogen receptors (ER) are present in various reproductive tissues as well as in other tissues not considered classical targets for estrogen. A variety of alternatively spliced ER variants which co-exist with the wild-type receptor has also been described in many tissues. We analyzed the presence of both wild-type and variant receptors from normal human tissues of various origin using semi-nested PCR and direct automated sequence of the amplified products. We demonstrate that many normal human tissues of various origin contain a number of spliced variants of the estrogen receptor that co-exist with the wild-type receptor. Variants lacking exons 2, 4, 5, and 7 are detected in a variety of normal human tissues.

Adolescent↗