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Biomedical subjects

S Y Cheng

Publications and source records attributed to S Y Cheng.

At least 19 recordsLinked to original sources

Estimation of atmospheric mixing heights over large areas using data from airport meteorological stations.

For this study, ground and sounding meteorological data at 16 airports were used for estimating the atmospheric mixing heights in Hebei Province of China, including Beijing and Tanjing areas. Three methods were compared for this purpose, which are the dry adiabatic method, the conventional Nozaki model, and a modified Nozaki model. The feasibility of using airport meteorological data to determine mixing heights in large area was verified through the use of measured mixing heights and observed SO2 vertical profiles. The study not only estimated the mixing heights over large areas but also compared different early morning sounding temperature profiles to identify feasibility of using 2:00 a.m. sounding profiles to estimate mixing height by the dry adiabatic method. The paper also described the mixing heights over different areas such as mountain, sea boundary and plain areas. The results have considerable significance for air quality prediction and environmental management. A novel approach to estimation of atmospheric mixing heights over large area is introduced, requiring only the input of readily available airport meteorological data.

Air Movements↗

Vascular endothelial growth factor isoforms display distinct activities in promoting tumor angiogenesis at different anatomic sites.

The gene for the major angiogenic factor, vascular endothelial growth factor (VEGF), encodes several spliced isoforms. We reported previously that overexpression of two VEGF isoforms, VEGF(121) and VEGF(165), by human glioma U87 MG cells induced tumor-associated intracerebral hemorrhage, whereas expression of a third form, VEGF(189), did not cause vessel rupture. Here, we test whether these VEGF isoforms have distinct activities for enhancing vascularization and growth of gliomas in mice. U87 MG cells that overexpressed VEGF(165) or VEGF(189) grew more rapidly than the parental cells in both s.c. and intracranial (i.c.) locations. However, cells that overexpressed VEGF(121) only showed enhancement of i.c. tumor growth but had a minimal effect on s.c. glioma progression. At both anatomical sties, VEGF(165) and VEGF(189) strongly augmented neovascularization, whereas VEGF(121) only increased vessel density in brain tumors. In each type of glioma, expression of VEGF receptors -1 and -2 largely phenocopied the tumor vasculature, because increased VEGF/VEGF receptor-activated microvessel densities were strongly correlated with the angiogenicity and tumorigenicity elicited by the VEGF isoforms at both anatomical sites. One notable difference between the sites was the expression of vitronectin, a prototypic ligand of alpha(v)beta(3) and alpha(v)beta(5) integrins, detected in i.c. but not in s.c., gliomas. Endothelial cell migration stimulated by VEGF(121) was potentiated by vitronectin to a greater extent than that stimulated by VEGF(165). This data demonstrates that VEGF isoforms have distinct activities at different anatomical sites and suggest that the microenvironment of different tissues affects the function of VEGF isoforms.

Animals↗

An isoform of branched-chain aminotransferase is a novel co-repressor for thyroid hormone nuclear receptors.

The functions of thyroid hormone receptors (TRs) are regulated by a host of co-regulatory proteins. Tissue-specific expression of these co-regulators leads to distinct expression patterns and regulation of thyroid hormone (T3) target genes in tissues. Previously we have found that human colon carcinoma RKO cells exhibit strong T3-independent transcriptional activity. We therefore searched for co-regulatory proteins in RKO cells using a yeast two-hybrid system with the intact TRbeta1 as bait. One of the three positive clones, designated as P3, was identified to be an isoform of human mitochondria branched-chain aminotransferase (BCATm). P3 was a spliced variant of BCATm with an internal 12-amino acid deletion near the carboxyl-terminal region and was abundantly expressed in RKO cells. The expressed protein localized both to the mitochondria and the nucleus of transfected CV1 cells. P3 physically interacted with TRbeta1 in a T3-independent manner that led to the inhibition in binding of TRbeta1 to thyroid hormone-responsive element. P3 not only enhanced the repressor activity of the unliganded TR but also repressed the ligand-dependent activation of TR. This repression was reversed by treatment of cells with trichostatin A, suggesting that in addition to the inhibition of DNA binding, the repression activity of P3 on TR may also be mediated by histone deacetylase activity. Thus, unlike the currently known co-repressors, P3 is a novel ligand-independent co-repressor for TR.

Animals↗

Brain glucose utilization in mice with a targeted mutation in the thyroid hormone alpha or beta receptor gene.

Brain glucose utilization is markedly depressed in adult rats made cretinous after birth. To ascertain which subtype of thyroid hormone (TH) receptors, TRalpha1 or TRbeta, is involved in the regulation of glucose utilization during brain development, we used the 2-[(14)C]deoxyglucose method in mice with a mutation in either their TRalpha or TRbeta gene. A C insertion produced a frameshift mutation in their carboxyl terminus. These mutants lacked TH binding and transactivation activities and exhibited potent dominant negative activity. Glucose utilization in the homozygous TRbetaPV mutant mice and their wild-type siblings was almost identical in 19 brain regions, whereas it was markedly reduced in all brain regions of the heterozygous TRalpha1PV mice. These suggest that the alpha1 receptor mediates the TH effects in brain. Inasmuch as local cerebral glucose utilization is closely related to local synaptic activity, we also examined which thyroid hormone receptor is involved in the expression of synaptotagmin-related gene 1 (Srg1), a TH-positively regulated gene involved in the formation and function of synapses [Thompson, C. C. (1996) J. Neurosci. 16, 7832-7840]. Northern analysis showed that Srg1 expression was markedly reduced in the cerebellum of TRalpha(PV/+) mice but not TRbeta(PV/PV) mice. These results show that the same receptor, TRalpha1, is involved in the regulation by TH of both glucose utilization and Srg1 expression.

Age Factors↗

Pancreatic cancer cell-derived vascular endothelial growth factor is biologically active in vitro and enhances tumorigenicity in vivo.

Vascular endothelial growth factor (VEGF) is a potent angiogenic stimulator that acts by binding to high-affinity transmembrane receptors. Although both VEGF and its receptors are overexpressed in human pancreatic ductal adenocarcinoma (PDAC), this malignancy is not generally considered to be highly vascular. It is not known, therefore, whether the abundance of VEGF in PDAC is biologically relevant. To address this issue, we measured the angiogenic effects of pancreatic cancer cell-derived VEGF in an in vitro endothelial cell proliferation assay and characterized the consequences of suppressing VEGF expression on pancreatic tumor growth in an athymic nude mouse model. We found that human pancreatic cancer cell lines secrete large quantities of biologically active VEGF into conditioned medium (CM). Stable transfection of an anti-sense VEGF(189) (AS-VEGF(189)) expression construct into PANC-1 pancreatic cancer cells resulted in decreased VEGF expression and secretion, a decreased capacity of the resultant CM to enhance endothelial cell proliferation and a significant attenuation of tumor cell proliferation in vitro. Furthermore, when injected into athymic nude mice, AS-VEGF(189)-expressing cells exhibited an 80% decrease in tumor growth compared with control cells. These results support the hypothesis that VEGF promotes pancreatic cancer growth in vivo and suggest that anti-VEGF therapy may be useful in the treatment of this disease.

Animals↗

The time-course change of nitrogenous excretion in the Kuruma shrimp Penaeus japonicus following nitrite exposure.

Penaeus japonicus (12.83 +/- 1.24 g) which were exposed individually to 0.002 (control), 0.076, 0.362, 0.719 and 1.433 mM nitrite at 30 ppt of salinity were examined for hemolymph ammonia, urea and nitrite, and nitrogenous excretion after 3, 6, 12, 24 and 48 h, respectively. Hemolymph nitrite and hemolymph urea increased directly with ambient nitrite and exposure time, whereas hemolymph ammonia was inversely related to ambient nitrite and exposure time. Specific excretions of total-N (total nitrogen), ammonia-N, urea-N and organic-N (organic nitrogen) increased directly with ambient nitrite and exposure time. The contribution of ammonia-N excretion and urea-N excretion in the total-N excreted by the control shrimp was 41.7-90.8 and 2.8-10.5%, respectively. The contribution of ammonia-N in the total-N excreted by P. japonicus decreased to 10.0 and 3.8%, when they were exposed for 24 h to 0.076 and 1.433 mM nitrite, respectively. The contribution of urea-N excretion increased to 58.7 and 21.4%, and the organic-N excretion increased to 31.3 and 74.8% in the total-N excreted by the shrimp following 24 h exposure to 0.076 and 1.433 mM nitrite, respectively. It was concluded that P. japonicus following 24 h exposure to nitrite as low as 0.076 mM increased its ammonia-N excretion by a factor of 1.9, its urea-N excretion by 200, and its organic-N excretion by 37, as compared to those in the control solution.

Ammonia↗

Sedation for refractory symptoms of terminal cancer patients in Taiwan.

This study assessed sedation in terminal cancer patients in terms of three characteristics: frequency; relationship to intractable symptoms; and the extent to which medical staff, family, and patients found sedation to be ethically acceptable and efficacious. Two hundred seventy-six consecutive patients, who were admitted to the palliative care unit of National Taiwan University Hospital in Taiwan between August 1998 and the end of May 1999, were enrolled. A recording form was completed every day. This included demographic data, pain and common symptom scores, and the use of sedation in the terminal phase. Seventy (27.9%) of 251 patients who died received sedation. Sedation was administered to relieve agitated delirium in 40 (57.1%), dyspnea in 16 (22.8%), severe pain in 7 (10%) and insomnia in 5 (7.2%). The drugs used for sedation were haloperidol in 35 (50%), midazolam in 17 (24.3%), and rapidly increasing dosage of morphine in 9 (12.9%). In fewer than half (42.9%) of the patients, sedation was with the consent of both patient and family, and half (50%) had the consent of family alone. The overwhelming majority of medical staff and family felt the decision to use terminal sedation was ethically acceptable. There was no significant difference in survival time between sedated and non-sedated patients (28.49 vs. 24.71 days, t = -0.791, P = 0.430). Positive ethical acceptability and higher satisfaction with symptom control with terminal sedation were found in both medical staff and family in this study. Further work is needed to find the most appropriate time of intervention and to improve management of refractory symptoms in dying patients.

Adolescent↗

Estimation of atmospheric mixing heights using data from airport meteorological stations.

In this study, ground and sounding meteorological data at the Beijing Airport during 1991 to 1995 were used for estimating the local atmospheric mixing heights. Three methods were compared for this purpose, including the dry adiabatic method, the Nozaki model, and a modified Nozaki model. The modification of the Nozaki model included joint frequencies for wind-velocity and stability based on the complexities of local meteorological conditions. The estimated values from the three methods were verified through the data measured by the Beijing Meteorological Center. The results indicated that the dry adiabatic method has the best performance. The modified Nozaki model was better than the commonly used. This study is a new attempt in utilizing airport meteorological data to estimate atmospheric mixing heights.

Air Movements↗

Silencing of Wnt signaling and activation of multiple metabolic pathways in response to thyroid hormone-stimulated cell proliferation.

To investigate the transcriptional program underlying thyroid hormone (T3)-induced cell proliferation, cDNA microarrays were used to survey the temporal expression profiles of 4,400 genes. Of 358 responsive genes identified, 88% had not previously been reported to be transcriptionally or functionally modulated by T3. Partitioning the genes into functional classes revealed the activation of multiple pathways, including glucose metabolism, biosynthesis, transcriptional regulation, protein degradation, and detoxification in T3-induced cell proliferation. Clustering the genes by temporal expression patterns provided further insight into the dynamics of T3 response pathways. Of particular significance was the finding that T3 rapidly repressed the expression of key regulators of the Wnt signaling pathway and suppressed the transcriptional downstream elements of the beta-catenin-T-cell factor complex. This was confirmed biochemically, as beta-catenin protein levels also decreased, leading to a decrease in the transcriptional activity of a beta-catenin-responsive promoter. These results indicate that T3-induced cell proliferation is accompanied by a complex coordinated transcriptional reprogramming of many genes in different pathways and that early silencing of the Wnt pathway may be critical to this event.

Animals↗

Special features of non-melanoma skin cancer in Hong Kong Chinese patients: 10-year retrospective study.

OBJECTIVE: To determine the incidence and clinical characteristics of non-melanoma skin cancer in Hong Kong Chinese patients. DESIGN: Retrospective study. SETTING: Social Hygiene Services, Hong Kong. PATIENTS: Records of 528 Chinese patients with a histological diagnosis of non-melanoma skin cancer from 1990 to 1999 were reviewed. MAIN OUTCOME MEASURES: Demographic data, site and clinical type of cancer, predisposing factors, history, recurrence, and the development of new skin cancers. RESULTS: Non-melanoma skin cancer is uncommon but not rare among the Chinese population in Hong Kong. The incidence of newly diagnosed basal cell carcinoma in 1990 was 16.0 per 10,000 new skin case attendances and, in 1999, the incidence was 31.8 per 10,000 new skin case attendances. The corresponding figures for squamous cell carcinoma in 1990 and 1999 were 6.9 and 11.6 per 10,000 new skin case attendances. The incidence of basal cell carcinoma among the Hong Kong Chinese population in 1990 and 1999 was 0.32 and 0.92 per 100,000, respectively, whereas that of squamous cell carcinoma was 0.16 and 0.34 per 100,000, respectively. Demographic data and the site distribution of non-melanoma skin cancer were comparable to those reported in Caucasians living in North America and Europe, but different from those in Caucasians living in Australia and Hawaii. Pigmented basal cell carcinoma was the most common type of non-melanoma skin cancer (60.1%) in Chinese patients, in contrast with rodent ulceration in Caucasian. Multiple skin cancers, recurrence, and subsequent new skin cancers were less frequently observed than in studies of Caucasians. CONCLUSION: When compared with reported findings in Caucasians, Chinese patients show differences in the clinical type and multiplicity of lesions, predisposing factors, recurrence, and subsequent new skin cancer rates for non-melanoma skin cancer. Pigmented basal cell carcinoma seems to be an important differential diagnosis with regard to pigmented lesions in the Chinese population.

Aged↗

Repeat polymorphisms within gene regions: phenotypic and evolutionary implications.

We have developed an algorithm that predicted 11,265 potentially polymorphic tandem repeats within transcribed sequences. We estimate that 22% (2,207/9,717) of the annotated clusters within UniGene contain at least one potentially polymorphic locus. Our predictions were tested by allelotyping a panel of approximately 30 individuals for 5% of these regions, confirming polymorphism for more than half the loci tested. Our study indicates that tandem-repeat polymorphisms in genes are more common than is generally believed. Approximately 8% of these loci are within coding sequences and, if polymorphic, would result in frameshifts. Our catalogue of putative polymorphic repeats within transcribed sequences comprises a large set of potentially phenotypic or disease-causing loci. In addition, from the anomalous character of the repetitive sequences within unannotated clusters, we also conclude that the UniGene cluster count substantially overestimates the number of genes in the human genome. We hypothesize that polymorphisms in repeated sequences occur with some baseline distribution, on the basis of repeat homogeneity, size, and sequence composition, and that deviations from that distribution are indicative of the nature of selection pressure at that locus. We find evidence of selective maintenance of the ability of some genes to respond very rapidly, perhaps even on intragenerational timescales, to fluctuating selective pressures.

Algorithms↗

The orphan nuclear receptor Ear-2 is a negative coregulator for thyroid hormone nuclear receptor function.

Thyroid hormone (T3) nuclear receptors (TR) are ligand-dependent transcription factors which regulate growth, differentiation, and development. One emerging hypothesis suggests that TR mediate these diverse effects via a large network of coregulators. Recently, we found that TR-mediated transcriptional responses varied in six cell lines derived from different tissues. We therefore used human TR subtype beta1 (TRbeta1) as bait to search for coregulators in human colon carcinoma RKO cells with a yeast two-hybrid system. RKO cells exhibited T3-dependent and -independent transcriptional activation. One of the three positive clones was identified as Ear-2, which is a distant member of the chick ovalbumin upstream promoter-transcription factors of the orphan nuclear receptor family. The physical interaction between Ear-2 and TRbeta1 was further confirmed by specific binding of Ear-2 to glutathione S-transferase-TRbeta1. In addition, Ear-2 was found to associate with TRbeta1 in cells. As a result of this physical interaction, binding of TRbeta1 to the T3 response elements was inhibited. Using reporter systems, we found that both the basal activation and the T3-dependent activation mediated by TRbeta1 were repressed by Ear-2 in CV1 cells. In RKO cells, however, the T3-independent transcriptional activity was more sensitive to the repression effect of Ear-2 than the T3-dependent transcriptional activity. The repression effect of Ear-2 was reversed by steroid hormone receptor coactivator 1. These results suggest that TR-mediated responses reflect a balance of corepressors and coactivators in cells. These findings further strengthen the hypothesis that the diverse activities of TR are achieved via a large network of coregulators that includes Ear-2.

Animals↗

Ethical dilemmas in palliative care: a study in Taiwan.

OBJECTIVES: To investigate the incidence and solution of ethical dilemmas in a palliative care unit. DESIGN: Health care workers recorded daily all dilemmas in caring for each patient. SETTING: Palliative care unit of National Taiwan University Hospital in Taiwan. PATIENTS: Two hundred and forty-six consecutive patients with terminal cancer during 1997-8. MAIN MEASUREMENT: Ethical dilemmas in the questionnaire were categorised as follows: telling the truth; place of care; therapeutic strategy; hydration and nutrition; blood transfusion; alternative treatment; terminal sedation; use of medication, and others. RESULTS: The type and frequency of ethical dilemmas encountered were: place of care (33.3%); truth-telling (32.1%); hydration and nutrition (25.2%); therapeutic strategy (24.8%), and use of medication (19.1%). Ethical problems relating to the place of care and to therapeutic strategy were unlikely to be solved with increased hospital stay and some ethical dilemmas remained unsolved even in the final week in hospital, including place of care (23.2%), truth-telling (17.1%) and therapeutic strategy (11.4%). Problems of truth-telling occurred in nearly half (42.6%) of patients over sixty-five-years-old. Conflicts about blood transfusion were experienced in all patients below 18-years-old, and the dilemmas concerning the place of care occurred most frequently with head and neck cancer patients (43.8%). CONCLUSIONS: The solution of ethical dilemmas required refocusing by medical professionals on the importance of continuing communication. Improved ethical training for professionals would contribute to solving the moral dilemmas of palliative care.

Aged↗

Trace elements and lipid peroxidation in human seminal plasma.

In the present study, the concentrations of copper, iron, zinc, and malondialdehyde in human seminal plasma were measured and correlated with the sperm count and motility in human semen. Copper, iron, and zinc were analyzed by atomic absorption spectrometry, whereas malondialdehyde was measured by high-performance liquid chromatography. The malondialdehyde concentrations in asthenospermia and oligoasthenospermia were significantly higher than in normospermia. Copper and iron levels were higher in asthenospermia, whereas the zinc concentrations in both oligospermia and asthenospermia were lower than in normal controls. A negative correlation (r = -0.28, p < 0.05) between the malondialdehyde concentration and sperm motility was observed in the abnormal groups. There was no association among copper, iron, zinc, and malondialdehyde in seminal plasma. We concluded that changes in trace elements may be related to sperm quality and that lipid peroxidation, although it is not promoted in the seminal plasma by copper or iron or ameliorated by zinc, may be involved in the loss of sperm motility.

Humans↗

Chronic exercise enhances vascular responses to clonidine in rats by increasing endothelial alpha2-adrenergic receptor affinity.

Chronic exercise increases endothelium-dependent vasodilating responses. To investigate whether endothelial alpha2-adrenergic receptor upregulation is involved in the enhancement of clonidine-induced vasorelaxation by chronic exercise, 4-week-old male Wistar rats were used. They were divided into control and exercise groups. The trained animals ran on a treadmill at a moderate intensity for 60 min per day, 5 days per week for 10 weeks in total. Resting heart rates were measured by a tail-cuff method to confirm training effects. After training, rings of the thoracic aorta were prepared to evaluate vasodilating responses to clonidine, an alpha2 agonist. Released endothelium-derived relaxing factors were pharmacologically identified by treatment of N(omega)-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, or tetraethylammonium chloride, an endothelium-derived hyperpolarization factor (EDHF) inhibitor. Receptor binding assays were performed by using 3H-labeled clonidine as a tracer. We found that chronic exercise enhanced vascular responses to clonidine by stimulating the release of both NO and EDHF. It also increased the binding affinity of endothelial cell alpha2 receptor without changing the number of binding sites. Therefore, the elevated vasorelaxing responses to clonidine after chronic exercise may be partially resulted from an increase in endothelial alpha2 receptor binding affinity.

Adrenergic alpha-Agonists↗

Expression of the mutant thyroid hormone receptor PV in the pituitary of transgenic mice leads to weight reduction.

Resistance to thyroid hormone (RTH) is a genetic disease caused by mutations of the thyroid hormone receptor beta gene (TRbeta). One of the symptoms in some affected individuals is growth retardation. To understand the molecular basis of growth retardation in these patients with RTH, a transgenic mouse was prepared in which the expression of the TRbeta1 mutant PV was targeted to the pituitary using the promoter of the glycoprotein hormone alpha-subunit. The PV mutant was originally identified in a patient with severe growth impairment. The PV mutation is a C-insertion at codon 448 of the TRbeta gene and leads to a frame-shift of the carboxyl-terminal 14 amino acids of TRbeta1, resulting in total loss of triiodothyronine (T3) binding and transcriptional activation. PV was selectively expressed in the pituitary of the transgenic mouse and not in other tissues examined. The transgenic mice showed a significant impairment in weight gain. However, no changes in the serum level of thyroid-stimulating hormone were seen, and no elevation of thyroid hormones was detected in the transgenic mice. The circulating levels of growth hormone and insulin-like growth factor I were not affected in the transgenic mice, suggesting that the growth impairment in RTH is complex and is mediated by pathways that are yet to be elucidated.

Animals↗

Tissue-specific differential repression of gene expression by a dominant negative mutant of thyroid hormone beta1 receptor.

Resistance to thyroid hormone (RTH) is a genetic disease caused by the mutations of the thyroid hormone beta receptor (TRbeta) gene, producing receptors with a dominant negative action. The present study addressed the question as to whether tissue-specific factors modulate the dominant negative function in different tissues. We prepared stably transfected pituitary GH3 (GH3-PV) and liver SK-Hep-1 (SK-Hep-1-PV) cell lines with a potent dominant negative mutant, PV. The growth hormone (GH) and the malic enzyme genes (ME) in GH3 and SK-Hep-1, respectively, are directly regulated by the thyroid hormone, 3,3,'5-triiodo-L-thyronine (T3). The ratio of the expressed PV/endogenous TRbeta1 proteins was approximately 20 and 5 for GH3-PV and SK-Hep-1-PV cells, respectively. However, the T3-activated expression of the GH gene in GH3-PV and ME gene in SK-Hep-1-PV was repressed by approximately 30% and 90%, respectively, indicating the lack of correlation of PV/TRpbeta1 protein ratio with the dominant negative potency of mutant PV. Furthermore, the synergistic effect of the pituitary-specific factor 1 on the TR-mediated GH promoter activity was not repressed by mutant PV. Taken together, these results suggest that the dominant negative effect of mutant TR is variable in the tissues studied.

Animals↗