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Biomedical subjects

Y Li

Publications and source records attributed to Y Li.

At least 145 records · Page 8Linked to original sources

Identification and analysis of tumour-associated antigens in hepatocellular carcinoma.

To identify tumour and tumour-associated antigens in patients with hepatocellular carcinoma (HCC) one may find potential diagnostic markers and immunotherapeutic targets. In the current study, 30 distinct antigens reactive with serum IgG from HCC patients were identified by serological analysis of cDNA expression libraries (SEREX). The mRNA expression patterns of 14 of these 30 antigens were altered in cancer as further revealed by cDNA microarray, with upregulation for nine and downregulation for five antigens. One of the upregulated antigens was cancer-testis (CT) antigen (CAGE), which had been previously reported to be expressed exclusively in normal gametogenic tissues and aberrantly expressed in a variety of cancer cells. In our study, CAGE mRNA was expressed in 39.4% of HCC patients, 73.3% of patients with gastric cancer and 30.8% of patients with colorectal cancer. Antibodies against CAGE protein were detected in approximately 5.1% of the sera from HCC patients, 8.3% of that from gastric cancer patients and 7.3% of that from colorectal cancer patients. The relative high incidence of CAGE in cancer cells makes it a potential target for vaccine design. Another antigen of great interest is transgelin 2. The overexpression of transgelin 2 mRNA in a large per cent (69%) of HCC points to its potential as a diagnostic marker for HCC.

Antigens, Neoplasm↗

Enzymes as modulators in malignant transformation.

Experimental data suggest that sex steroids have a role in the development of breast and prostate cancers. The biological activity of sex steroid hormones in target tissues is regulated by several enzymes, including 17beta-hydroxysteroid dehydrogenases (17HSD). Changes in the expression patterns of these enzymes may significantly modulate the intracellular steroid content and play a pathophysiological role in malignant transformation. To further clarify the role of 17HSDs in breast cancer, we analyzed the mRNA expressions of the 17HSD type 1, 2, and 5 enzymes in 794 breast carcinoma specimens. Both 17HSD type 1 and 2 mRNAs were detected in normal breast tissue from premenopausal women but not in specimens from postmenopausal women. Of the breast cancer specimens, 16% showed signals for 17HSD type 1 mRNA, 25% for type 2, and 65% for type 5. No association between the 17HSD type 1, 2, and 5 expressions was detected. The patients with tumors expressing 17HSD type 1 mRNA or protein had significantly shorter overall and disease-free survival than the other patients. The expression of 17HSD type 5 was significantly higher in breast tumor specimens than in normal tissue. The group with 17HSD type 5 overexpression had a worse prognosis than the other patients. Cox multivariate analyses showed that 17HSD type 1 mRNA, tumor size, and ERalpha had independent prognostic significance. Using an LNCaP prostate cancer cell line, we developed a cell model to study the progression of prostate cancer. In this model, androgen-sensitive LNCaP cells are transformed in culture conditions into more aggressive, androgen-independent cells. The model was used to study androgen and estrogen metabolism during the transformation process. Our results indicate that substantial changes in androgen and estrogen metabolism occur in the cells during the process. A remarkable decrease in oxidative 17HSD activity was seen, whereas reductive activity seemed to increase. Since local steroid metabolism controls the bioavailability of active steroid hormones of target tissues, the variations in steroid-metabolizing enzymes during cancer progression may be crucial in the regulation of the growth and function of organs.

17-Hydroxysteroid Dehydrogenases↗

The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer.

BACKGROUND: We examined the clinical relevance of skeletal-related events (SREs) for health state preferences, pain and health-related quality of life in patients with advanced prostate cancer and a history of bone metastases. PATIENTS AND METHODS: Data were from a clinical trial of zoledronic acid versus placebo in the treatment of SREs associated with advanced prostate cancer metastatic to bone. Patients (n=248) were included if they experienced an SRE during the study. Outcome measures were assessed at fixed intervals. We used mixed-effects models to estimate changes in outcomes after each patient's first SRE. RESULTS: There were clinically meaningful and statistically significant declines in physical well-being after: radiation and pathologic fractures; functional well-being after radiation; and emotional well-being after radiation and pathologic fractures. There also were meaningful and significant declines in preference and utility scores after radiation and fracture. Pain intensity declined after radiation, but not after other SREs; no other pain measure changed substantively. CONCLUSIONS: SREs have important and significant effects on measures of health-related quality of life in men with prostate cancer. Treatments that prevent SREs may not demonstrate corresponding effects on outcomes if the effects of SREs occur between scheduled outcome assessments. Implications for trial design are discussed.

Aged↗

Perceptions of temperature, moisture and comfort in clothing during environmental transients.

A study has been carried out to investigate the psychophysical mechanisms of the perception of temperature and moisture sensations in clothing during environmental transients. A series of wear trials was conducted to measure the psychological perception of thermal and moisture sensations and the simultaneous temperature and humidity at the skin surface, fabric surface and in the clothing under simulated moderate rain conditions. Jumpers made from wool and acrylic fibres were used in the trial. Analysis has been carried out to study the relationship between psychological perceptions of temperature and moisture and the objectively measured skin and fabric temperatures and relative humidity in clothing microclimate. The perception of warmth seems to follow Fechner's law and Stevens' power law, having positive relationships with the skin temperature and fabric temperatures. The perception of dampness appears to follow Fechner's law more closely than Stevens' power law with a negative relationship with skin temperature, and is nonlinearly and positively correlated with relative humidity in clothing microclimate. The perception of comfort is positively related to the perception of warmth and negatively to the perception of dampness. This perception of comfort is positively related to the skin temperature, which appears to follow both Fechner's law and Stevens' law, also non-linearly and negatively related to relative humidity in clothing microclimate.

Adult↗

Genetic characterization of H5N1 avian influenza viruses isolated in southern China during the 2003-04 avian influenza outbreaks.

The recent H5N1 avian influenza outbreaks in Asia spread over more than 8 countries. It has caused enormous economic loss and grand challenges for the public health. During these breakouts we isolated three strains of H5N1 Avian Influenza Virus (AIV) from chickens and one from duck in different farms of Southern China. We completely sequenced these four AIVs. Molecular characterization demonstrated that these strains retain the reported H5N1 AIV sequence properties relevant to virus virulence and host adaptation. Phylogeny results demonstrated that three of these isolates (except A/Chicken/Guangdong/174/04) were closely linked to other H5N1 AIVs isolated from the recent H5N1 outbreaks in Asia. Six of 8 segments (except PA and M) of A/Chicken/Guangdong/174/04 also shares a close linkage to other H5N1 AIVs isolated from the recent H5N1 outbreaks. However, the PA gene of A/Chicken/Guangdong/174/04 and another H5N1 strain forms a distinct subgroup along with an H6N1 AIV, and the M gene of A/Chicken/Guangdong/174/04 shows a close linkage to some H5N1 AIVs from aquatic species in China. Our findings suggest that a new genotype of AIV (in addition to previous reported ones) was present during the 2003-04 Asian bird flu outbreaks and that continuing virus surveillance of AIVs be conducted to monitor the evolutionary paths of the A/Chicken/Guangdong/174/04-like AIVs.

Animals↗

Proneness to psychological distress and risk of Alzheimer disease in a biracial community.

Persons without dementia residing in a biracial community completed a brief scale of proneness to psychological distress, and 1,064 were subsequently examined for incident Alzheimer disease (AD) 3 to 6 years later. In analyses controlling for selected demographic and clinical variables, persons prone to distress were 2.4 times more likely to develop AD than persons not distress prone. This effect was substantially stronger in white persons compared to African Americans.

Black or African American↗

High iodine intake is a risk factor of post-partum thyroiditis: result of a survey from Shenyang, China.

The aim of the present study is to obtain the epidemiological data on post-partum thyroiditis (PPT) firstly in Chinese women, and to tryto evaluate whether excessive intake of iodine in post-partum women imposes any danger of occurring PPT. Sixty hundred and ten pregnant women were involved in the cohort just before delivery. Four hundred and eighty-eight (80%) of them accepted taking part in follow-ups more than 6 months post-partum. A blood sample was taken from participants before delivery and every 3 months post-partum for testing of serum TSH, thyroid autoantibodies. Free T3 (FT3), free T4 (FT4) and TSH receptor antibody (TRAb) were detected if TSH was abnormal. The iodine nutrition was evaluated according to the mean level of the fasting urinary iodine excretions at different times during the studying period, and participants were subgrouped into 3 categories with low, adequate and high iodine intake. For those participants who had thyroid dysfunction within 6 months post-partum, the follow-up persisted for 1 yr. Of 488 pregnant women, PPT developed in 11.9% (58/488). Given overt and subclinical PPT, the prevalence was 7.17% (no.=35) and 4.71% (no.=23), respectively. There was a strong association between the presence of thyroid peroxidase antibody (TPOAb) at delivery and the risk of developing PPT [RR=6.76, 95% (CI) 4.42-10.34]. Overt cases had much higher titers of TPOAb than subclinical patients (all p<0.05). The median urinary iodine (MUI) of patients with PPT was significantly higher than that of healthy women (231.93 vs 199.88 microg/l p=0.00153). Both the prevalence of PPT and positive TPOAb rise with the increment of iodine intakes. Pregnant women with high iodine intake had more risk of developing PPT when compared with those with low iodine intake (RR=2.92, 95%CI 1.31-6.50). We concluded that positive TPOAb was of value for predicting the occurrence and severity of PPT, and a high iodine intake was a risk factor triggering PPT.

Adult↗

Elevated allergen-induced IL-13 secretion predicts IgE elevation in children ages 2-5 years.

It is unclear if early immune responses to allergens, specifically Th1 and Th2 cytokine production, predict later immune responses, including increased IgE levels. In a group of children (n = 151) with a parental history of allergy or asthma followed from ages 2 through 5 years, we examined IL-13, IL-4, and IFN-gamma secretion by peripheral blood mononuclear cells in response to phytohemagglutinin (PHA), and to dust mite (Der f 1), cockroach (Bla g 2), and cat (Fel d 1) allergens in relation to elevated IgE. Elevated IgE was defined either as a positive IgE-specific response to at least one allergen (dust mite, cockroach, cat, and ovalbumin) or as an elevated total IgE level above a specified cut-off value. In multivariate logistic regression models including 181 observations made between the age of 2 through 5 years and accounting for repeated measures, we found an association between increased IL-13 secretion in response to Der f 1 and elevated IgE (odds ratio [OR] = 1.21, 95% confidence interval [CI] = 1.09-1.34). Age did not modify this relationship. No association was found between allergen-induced IFN-gamma secretion and IgE production. Among the group of children with measurements made at age 4-5 (n = 70), IL-13 in response to Der f 1 (p = 0.046), and IL-4 in response to PHA (p = 0.04) were increased among children with elevated IgE. In a smaller subset of children with measurements made at both age 2-3 and age 4-5 (n = 36), IL-13 levels at age 2-3 were also significantly increased in response to Der f 1 (p = 0.01) and Fel d 1 (p = 0.002) among those with elevated IgE at age 4-5. In a group of children ages 2-5 years, there is an association between IL-13 and elevated IgE.

Allergens↗

Expressed sequence tags from the Yukon ecotype of Thellungiella reveal that gene expression in response to cold, drought and salinity shows little overlap.

Thellungiella salsuginea (also known as T. halophila) is a close relative of Arabidopsis that is very tolerant of drought, freezing, and salinity and may be an appropriate model to identify the molecular mechanisms underlying abiotic stress tolerance in plants. We produced 6578 ESTs, which represented 3628 unique genes (unigenes), from cDNA libraries of cold-, drought-, and salinity-stressed plants from the Yukon ecotype of Thellungiella. Among the unigenes, 94.1% encoded products that were most similar in amino acid sequence to Arabidopsis and 1.5% had no match with a member of the family Brassicaceae. Unigenes from the cold library were more similar to Arabidopsis sequences than either drought- or salinity-induced sequences, indicating that latter responses may be more divergent between Thellungiella and Arabidopsis. Analysis of gene ontology using the best matched Arabidopsis locus showed that the Thellungiella unigenes represented all biological processes and all cellular components, with the highest number of sequences attributed to the chloroplast and mitochondria. Only 140 of the unigenes were found in all three abiotic stress cDNA libraries. Of these common unigenes, 70% have no known function, which demonstrates that Thellungiella can be a rich resource of genetic information about environmental responses. Some of the ESTs in this collection have low sequence similarity with those in Genbank suggesting that they may encode functions that may contribute to Thellungiella's high degree of stress tolerance when compared with Arabidopsis. Moreover, Thellungiella is a closer relative of agriculturally important Brassica spp. than Arabidopsis, which may prove valuable in transferring information to crop improvement programs.

Algorithms↗

Osteopenia and impaired fracture healing in aged EP4 receptor knockout mice.

The EP4 receptor, one of the subtypes of the prostaglandin E2 (PGE2) receptor, plays a critical role in the anabolic effects of PGE2 on bone. However, its role in the maintenance of bone mass in aged animals and its role in fracture healing is not well known. Our studies addressed these issues by characterizing the skeletal phenotype of aged, EP4 receptor knockout (KO) mice, and by comparing fracture healing in aged KO mice versus wild type (WT) mice. There was no significant difference in body weight and femoral length between KO and WT mice at 15 to 16 months of age. Lower bone mass was seen radiographically in both axial and long bones of KO mice relative to WT mice. Micro-CT images of the distal femurs showed thinner cortices, fewer trabeculae, and a deteriorated trabecular network in KO mice. Total bone content, trabecular content, and cortical content, as assessed by pQCT in the distal femur, were lower in KO mice than WT controls. Histomorphometric measurements showed that trabecular bone volume and bone formation rate were significantly decreased whereas osteoclast number on trabecular surface and eroded surface on endocortical surface were significantly increased in KO mice. These data indicated that deleting the EP4 receptor resulted in an imbalance in bone resorption over formation, leading to a negative bone balance. The lower bone formation rate in EP4 KO mice was primarily due to decreased mineralizing surface, suggesting that the defect in overall bone formation was mainly due to the defect in osteoblastogenesis. Fracture healing was examined in KO and WT mice subjected to a transverse femoral fracture. Callus formation was significantly delayed as evidenced both radiographically and histologically in the fractured femurs of KO mice compared with those of WT mice. KO mice had significant decreases in total callus area, cartilaginous callus area, and bony callus area 2 weeks after fracture. By 4 weeks, complete bony bridging was seen in WT mice but not in KO mice. These data demonstrate that the absence of the EP4 receptor decreases bone mass and impairs fracture healing in aged male mice. Our findings indicate that the EP4 receptor is a positive regulator in the maintenance of bone mass and fracture healing.

Aging↗

NMR detection and one-dimensional imaging using the inhomogeneous magnetic field of a portable single-sided magnet.

A portable, nuclear magnetic resonance (NMR) probe is described which utilises the intrinsic inhomogeneity of the field produced by a single-sided magnet to provide spatial encoding of the NMR signal. The probe uses a longitudinally magnetized hollow cylinder, and a figure-8 radiofrequency (RF) surface coil. The system has been used to measure NMR relaxation times and one-dimensional NMR profiles of rubber phantoms.

Equipment Design↗

Neurochemical phenotype of vagal afferent neurons activated to express C-FOS in response to luminal stimulation in the rat.

UNLABELLED: The vagus nerve conveys meal-induced primary afferent responses to the brainstem. Electrophysiological studies indicate that luminal stimuli such as osmolarity and the digestion products of carbohydrates elicit powerful vagal nodose neuronal responses by activating serotonin 3 (5-hydroxytryptamine-3, 5-HT3) receptors on intestinal mucosal afferent fibers. To characterize the neurochemical phenotype of neurotransmitters in vagal nodose neurons that are activated by luminal stimulation, we examined c-fos protein (c-Fos) expression in response to luminal stimulation in conscious rats. A double-labeling technique using antisera to glutamate (Glu), substance P (SP), calcitonin gene-related peptide (CGRP), and somatostatin (SS) was used to determine the neurochemical profile of c-Fos-positive neurons. c-Fos immunoreactivity was insignificant in vehicle-treated rats. Luminal perfusions of NaCl (500 mOsm), tap water (5 mOsm), maltose (300 mmol/l), and 5-HT (10(-5) mol/l) each elicited a significant increase in the number of cells expressing c-Fos. Chronic vagotomy eliminated an increase in nodose neuronal c-Fos expression, and the 5-HT3 receptor antagonist granisetron significantly reduced it. Glu-, SP-, and CGRP-containing neurons represented 28%, 53%, and 19%, respectively, of the total population of nodose neurons. Few neurons contained SS. Double-labeling studies revealed that of the c-Fos-positive neurons responsive to hypertonic NaCl, 52%, 41%, and 3% exhibited immunoreactivity for Glu, SP, and CGRP, respectively. Of those responsive to tap water, 47%, 50%, and 4% exhibited immunoreactivity for Glu-, SP- and CGRP, respectively. In addition, 44%, 38%, and 8% of 5-HT-stimulated and 30%, 32%, and 5% of maltose-stimulated c-Fos-positive neurons exhibited, respectively, Glu, SP, and CGRP immunoreactivity. The few neurons that contained SS did not express c-Fos. CONCLUSIONS: Vagal primary afferent neurons that respond to 5-HT-dependent luminal stimuli, such as hyperosmolarity and maltose, contain mainly Glu and SP. These neurons appear to play an important role in the mediation of the vago-vagal reflex elicited by luminal stimuli.

Animals↗

Gender and environmental effects on regional brain-derived neurotrophic factor expression after experimental traumatic brain injury.

Alterations in brain-derived neurotrophic factor expression have been reported in multiple brain regions acutely after traumatic brain injury, however neither injury nor post-injury environmental enrichment has been shown to affect hippocampal brain-derived neurotrophic factor gene expression in male rats chronically post-injury. Studies have demonstrated hormone-related neuroprotection for female rats after traumatic brain injury, and estrogen and exercise both influence brain-derived neurotrophic factor levels. Despite recent studies suggesting that exposure post-traumatic brain injury to environmental enrichment improves cognitive recovery in male rats, we have shown that environmental enrichment mediated improvements with spatial learning are gender specific and only positively affect males. Therefore the purpose of this study was to evaluate the effect of gender and environmental enrichment on chronic post-injury cortical and hippocampal brain-derived neurotrophic factor protein expression. Sprague-Dawley male and cycling female rats were placed into environmental enrichment or standard housing after controlled cortical impact or sham surgery. Four weeks post-surgery, hippocampal and frontal cortex brain-derived neurotrophic factor expression were examined using Western blot. Results revealed significant increases in brain-derived neurotrophic factor expression in the frontal cortex ipsilateral to injury for males (P=0.03). Environmental enrichment did not augment this effect. Neither environmental enrichment nor injury significantly affected cortical brain-derived neurotrophic factor expression for females. In the hippocampus ipsilateral to injury brain-derived neurotrophic factor expression for both males and females was half (49% and 51% respectively) of that observed in shams housed in the standard environment. For injured males, there was a trend in this region for environmental enrichment to restore brain-derived neurotrophic factor levels to sham values. However, there were robust increases in hippocampal brain-derived neurotrophic factor expression ipsilateral to the injury for injured females in environmental enrichment compared with both sham and injured females placed in standard housing (P<or=0.005). In the hippocampus contralateral to injury, there were also significant injury-related increases in brain-derived neurotrophic factor expression for females (P<or=0.05) that were not further augmented by environmental enrichment. These results show significant, region-specific gender differences in brain-derived neurotrophic factor expression with both injury and environmental enrichment that may be important for recovery. However, these data do not support a critical role for brain-derived neurotrophic factor in environmental enrichment mediated improvements with spatial learning.

Actins↗

Expression of 3beta-hydroxysteroid dehydrogenase type 1, P450 aromatase, and 17beta-hydroxysteroid dehydrogenase types 1, 2, 5 and 7 mRNAs in human early and mid-gestation placentas.

The placenta is responsible for the production of progesterone (P) and estrogens during human pregnancy. In this study, the expression of several key steroidogenic enzymes was investigated in different cell types of human placenta during early and mid-gestation by in situ hybridization. 3Beta-hydroxysteroid dehydrogenase type 1 (3beta-HSD1), P450 aromatase (P450arom) and 17beta-hydroxysteroid dehydrogenase type 1 (17HSD1) were expressed abundantly in syncytiotrophoblast (ST) cells. These three enzymes were also detected in some column cytotrophoblast (CCT) cells. 17HSD5 was found in intravillous stromal (IS) cells in low levels, suggesting that androgens may be synthesized and metabolized in the placenta. 17HSD7 was found in all types of placental cells. Moreover, 17HSD2 was localized in IS cells. The expression level of 17HSD2 gradually increased during pregnancy weeks 7-16, concurrently with the androgen production by the male fetus. The present study provides evidence that CCT and IS cells participate in P and estrogen biosynthesis, in addition to ST cells. 17HSD2 also converts 20alpha-dihydroprogesterone (20-OH-P) to P, whereas 17HSD5 and 17HSD7 inactivate P. Therefore, the action of 3beta-HSD1 and 17HSD2 on P biosynthesis in the placenta is countered by 17HSD5 and 17HSD7, which may provide an optimal level of P for the maintenance and progression of pregnancy.

17-Hydroxysteroid Dehydrogenases↗