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Biomedical subjects

X Huang

Publications and source records attributed to X Huang.

698 records · Page 39Linked to original sources

Association between metabolic gene polymorphisms and susceptibility to peripheral nerve damage in workers exposed to n-hexane: a preliminary study.

Chronic exposure to n-hexane may result in peripheral neuropathy. 2,5-Hexanedione (2,5-HD) has been identified as a toxic metabolite of n-hexane. The CYP2E1, CYP1A1 and GST genes are involved in the formation of 2,5-hexanedione from n-hexane as well as the elimination of 2,5-HD-formed electrophile, and these genes are highly polymorphic in the general population. A nested case-control study in an industrial cohort was conducted to evaluate the associations between polymorphisms in these metabolic genes and n-hexane-induced peripheral nerve damage. The study subjects included 22 cases, who worked in a printing factory with symptoms of peripheral nerve damage, and 163 controls, who came from the same factory of cases. DNA was extracted from blood samples and genotyping was conducted for CYP2E1 Pst, CYP2E1 Dra, CYP2E1 Ins96, CYP1A1 Msp, GSTT1 null, GSTM1 null and GSTP1 105V. Unconditional logistic regression was applied to estimate the odds ratio and 95% confidence intervals. There were no significant differences between the two groups regarding age, sex, smoking and alcohol status. A significant association between Dra polymorphism and peripheral nerve damage was found. The frequency of CYP2E1 Dra homozygous mutation in the case group (18.2%) was higher than that in the control group (3.7%, p=0.015). Individuals with homozygote genotype (CC) of CYP2E1 Dra had a significantly higher risk of peripheral nerve damage compared with those with DD genotype (adjusted OR=?.58, 95% CI=1.32-23.65) after n-hexane exposure duration, sex, age, smoking and alcohol status were adjusted. No significant association was found that CYP2E1 Pst, CYP2E1 Ins96, CYP1A1 Msp, GSTT1, GSTM1, GSTP gene polymorphisms associated with the susceptibility of peripheral nerve damage. These findings suggested that CYP2E1 gene might increase the susceptibility to n-hexane-induced peripheral damage.

Adult↗

Sensitive biomarker of polycyclic aromatic hydrocarbons (PAHs): urinary 1-hydroxyprene glucuronide in relation to smoking and low ambient levels of exposure.

The study was conducted in a Chinese population with occupational or environmental exposures to polycyclic aromatic hydrocarbons (PAHs). A total of 106 subjects were recruited from coke-oven workers (workers), residents in a metropolitan area (residents) and suburban gardeners (gardeners). All subjects were monitored twice for their personal exposures to PAHs. The biological samples were collected for measurements of 1-hydroxypyrene (1-OHP) and cotinine in urine. The geometric means of personal exposure levels of pyrene, benz(a)anthracene (BaA) and benzo(a)pyrene (BaP) in workers were 1.470, 0.978 and 0.805 microg m-3, respectively. The corresponding levels in residents were 0.050, 0.034 and 0.025 microg m-3; and those in gardeners were 0.011, 0.020 and 0.008 microg m-3, respectively. The conjugate of 1-OHP with glucuronide (1-OHP-G) is the predominant form of pyrene metabolite in urine and it showed strong associations with exposures not only to pyrene, but also to BaA, BaP and total PAHs. Most importantly, a significant difference in 1-OHP-G was even detected between the subgroups with exposures to BaP at < 0.010 and > 0.010 but < 0.020 microg m-3, suggesting that 1-OHP-G is a good marker that can be used for the risk assessment of BaP exposure at levels currently encountered in ambient air. Furthermore, multiple regression analyses of 1-OHP-G on PAHs exposure indicated that cigarette smoke was a major confounding factor and should be considered and adjusted for while using 1-OHP to estimate PAHs exposure.

Air Pollutants↗

Immune response against 3LL Lewis lung carcinoma potentiates the therapeutic efficacy of endostatin.

The ability of the antitumor immune response to potentiate the therapeutic efficacy of the antiangiogenic agent endostatin was investigated. The antitumor effects of endostatin were tested against weakly immunogenic 3LL Lewis lung carcinoma and its highly immunogenic variant 3LL-C75. Using in vivo Matrigel assay, it was found that the recombinant endostatin produced in the authors' laboratory has a potent antiangiogenic effect. Endostatin manifested a more potent antitumor effect against highly immunogenic 3LL-C75 than weakly immunogenic 3LL tumor. Endostatin induced regression of immunogenic 3LL-C75 tumor in 40% of C57BL/6 mice, whereas partial inhibition and no regression were found in mice bearing weakly immunogenic 3LL tumor. 3LL and 3LL-C75 cells produced similar amounts of Vascular Endothelial Growth Factor, and immunohistochemical analysis revealed that endostatin treatment reduced microvessel density in both 3LL and 3LL-C75 tumors. However, infiltration of T lymphocytes was observed in 3LL-C75 but not in 3LL tumors. These results suggest that the host's immune response may potentiate the antitumor effects of antiangiogenic agents. This possibility was further supported by findings that the antitumor activity of endostatin against 3LL-C75 tumor was lower in immunodeficient than in immunocompetent mice. Stimulation of immune response against 3LL tumor by vaccination with highly immunogenic 3LL-C75 cells substantially increased the antitumor effect of endostatain, resulting in a complete and permanent regression of 3LL tumor in 50% of mice. Tumor vaccination or endostatin treatment applied separately inhibited but did not induce regression of 3LL tumor. These results suggest that the combined attack against tumor cells and the tumor vascular system using antitumor immune mechanisms and antiangiogenic drugs can be a promising strategy for cancer treatment.

Angiogenesis Inhibitors↗

Mechanisms of reversal of adriamycin resistance in human ovarian carcinoma cell line by ultrasound.

The aim of this study was to investigate the reversal of adriamycin resistance in human ovarian cancer cells by ultrasound exposure from perspectives of apoptosis and mdr1 gene. Apoptosis was determined by flow cytometry and mdr1 level by reverse transcription-polymerase chain reaction (RT-PCR). Apoptosis indexes were improved in groups in which ultrasound exposures were applied. RT-PCR did not support that insonation-decreased mdr1 level. These findings suggested that the ultrasound-enhanced therapeutic efficacy was not mediated via modulating gene expression, and ultrasound maybe lowered thresholds for apoptosis and oncosis in chemoresistant ovarian cancer cells.

Antineoplastic Agents↗

Relaxin induces vascular endothelial growth factor expression and angiogenesis selectively at wound sites.

Relaxin is a reproductive hormone that has historically been characterized as being responsible for pubic ligament loosening and cervical ripening. Recently, relaxin has been associated with neovascularization of the endometrial lining of the uterus, potentially via specific induction of vascular endothelial growth factor. Previously conducted clinical studies using partially purified porcine relaxin have described relaxin's ability to stimulate the healing of ischemic wounds, suggesting that relaxin may also have angiogenic effects at sites of ischemic wound healing. In the present study, relaxin's angiogenic effects in the context of wound repair were tested in rodent models of angiogenesis and wound healing. Relaxin showed an ability to stimulate new blood vessel formation, particularly at ischemic wound sites, and to induce both vascular endothelial growth factor and basic fibroblast growth factor specifically in cells, presumably including macrophages, collected from wound sites. Resident macrophages collected from nonwound sites, such as the lung, did not show altered expression of these cytokines following relaxin administration. Because angiogenic wound cells are frequently macrophages, THP-1 cells, a cell line of monocyte lineage that binds relaxin specifically, were tested for and shown to induce vascular endothelial growth factor and basic fibroblast growth factor in response to relaxin. In conclusion, relaxin may be useful in the treatment of ischemic wounds by stimulating angiogenesis via the induction of vascular endothelial growth factor and basic fibroblast growth factor in wound macrophages.

Animals↗

Ultrastructure alterations in adriamycin-resistant and cisplatin-resistant human ovarian cancer cell lines exposed to nonlethal ultrasound.

Human ovarian cancer cell lines, SKOV3 and its adriamycin-resistant substrain SKOV3/ADR and COC1 and its cisplatin-resistant substrain COC1/DDP, were exposed to nonlethal ultrasound. Ultrastructures in sham-insonated and insonated cells were inspected by transmission electron microscopy, and cytochrome C in cytosol was determined by enzyme-linked immunosorbent assay. Ultrasound exposure led to no significant changes in SKOV3/ADR cells, but tumid mitochondria occurred in SKOV3 cells. Mitochondria changes were also detected in some exposed COC1 and COC1/DDP cells. Apoptotic bodies could be detected in either control or insonated COC1/DDP cells. A few exposed COC1/DDP cells became reticular. Cytochrome C in cytosol in exposed SKOV3/ADR cells was increased but that in exposed COC1/DDP cells was decreased. These findings revealed that the bioeffect of ultrasound on chemosensitive cells was not identical to that of chemoresistant ones, and ultrasound was a potential approach for treatment of drug-resistant ovarian cancers.

Antibiotics, Antineoplastic↗

Maternal weight differences do not explain ethnic differences in biochemical screening.

In previous work, we and others have shown that serum levels of alpha-fetoprotein, human chorionic gonadotropin, and estriol vary among the four commonly defined racial/ethnic groups seen in the United States: white, African-American, Asian, and Hispanic. We have suggested that better sensitivity and specificity could improve screening sensitivity and specificity. However, it has been argued that systematic weight differences among the groups could explain the variation. We evaluated the results from 208,257 patients having screening and found systematic weight differences. However, these differences were not as large as the racial/ethnic differences, showing that weight does not fully explain the discrepancy, and, therefore, four separate data bases give more accurate results.

Asian↗

Epulis: a clinicopathological study of 120 patients with emphasis on recurrent lesions.

A total of 138 surgical excision specimens from 120 patients presenting clinically with epulis was classified by histopathological criteria into giant cell-, granulomatous- and fibromatous-type lesions. Clinical data suggest that local irritants are an important pathogenetic factor. Histopathological analysis revealed that epulides represented self-limiting, reactive gingival overgrowths of granulation tissue displaying common morphologic features in all three histologic types. The transition of a given histologic type of epulis into another, as observed in recurrent lesions, is consistent with the concept of a common histogenetic entity.

Adolescent↗

Cardiac troponin I gene knockout: a mouse model of myocardial troponin I deficiency.

Troponin I is a subunit of the thin filament-associated troponin-tropomyosin complex involved in calcium regulation of skeletal and cardiac muscle contraction. We deleted the cardiac isoform of troponin I by using gene targeting in murine embryonic stem cells to determine the developmental and physiological effects of the absence of this regulatory protein. Mice lacking cardiac troponin I were born healthy, with normal heart and body weight, because a fetal troponin I isoform (identical to slow skeletal troponin I) compensated for the absence of cardiac troponin I. Compensation was only temporary, however, as 15 days after birth slow skeletal troponin I expression began a steady decline, giving rise to a troponin I deficiency. Mice died of acute heart failure on day 18, demonstrating that some form of troponin I is required for normal cardiac function and survival. Ventricular myocytes isolated from these troponin I-depleted hearts displayed shortened sarcomeres and elevated resting tension measured under relaxing conditions and had a reduced myofilament Ca sensitivity under activating conditions. The results show that (1) developmental downregulation of slow skeletal troponin I occurs even in the absence of cardiac troponin I and (2) the resultant troponin I depletion alters specific mechanical properties of myocardium and can lead to a lethal form of acute heart failure.

Animals↗

Effects of dissolved organic matter from animal waste effluent on chlorpyrifos sorption by soils.

The increased use of animal waste-derived effluents for irrigation could result in the enhanced movement of pesticides through complexation with dissolved organic materials. Batch equilibrium studies were conducted to measure the interaction among soil, chlorpyrifos [O,O-diethyl O-(3,5,6-trichloro-2-pyridyl) phosphorothioate], and dissolved organic matter (DOM) from poultry, swine, and cow waste-derived lagoon effluents. All DOM was found to have a strong affinity for chlorpyrifos, resulting in reduced sorption of chlorpyrifos by soil, thus the potential for DOM-enhanced mobility. Effluent DOM was observed to sorb to soils. Thus, for increasingly higher soil mass to solution volume ratios, the effect of chlorpyrifos association with water-borne DOM on sorption decreases significantly. For high soil mass to solution volume ratios typical of soil profiles in the landscape, the potential for DOM-enhanced transport will be greatly attenuated. Dissolved organic matter concentration and the nonpolar nature of DOM in the lagoon effluent decreased with increasing residence time in the cells of the lagoon system, thus reducing the potential for DOM-enhanced transport.

Adsorption↗

Apoptosis occurs in isolated and banked primary mouse hepatocytes.

Isolation and cryopreservation of freshly isolated hepatocytes is considered a standard procedure for the long-term storage of liver cells. However, most existing methods for banking hepatocytes do not allow sufficient recovery of viable cells to meet the needs of basic research or clinical trials of hepatocyte transplantation. The mechanisms underlying this poor rate of hepatocyte recovery are unknown. Although much of the cellular damage in freezing is caused by formation of ice crystals within the cells, this is largely prevented by the use of dimethyl sulfoxide (DMSO) and controlled rate freezing. As we demonstrated recently, necrosis does occur in primary hepatocytes following isolation and cryopreservation. In the present study, we explored the contribution of apoptosis, another form of cell death, in primary hepatocytes banked for transplantation. We evaluated apoptosis of C57BL/6J mouse primary hepatocytes using several different methods. Annexin binding and the TUNEL assay, in conjunction with flow cytometry and confocal laser scanning microscopy, revealed that the percentage of apoptotic cells was dramatically elevated in cryopreserved cells compared with that in the control group of unfrozen cells. DNA laddering detected by DNA electrophoresis in agarose gel also supported the presence of apoptosis in isolated and banked liver cells. Moreover, we found that the addition of glucose (from 10 to 20 mM) into the freezing solution (University of Wisconsin Solution) decreased the rate of apoptosis by 84% and improved the cell attachment at least fourfold in cryopreserved cells. These results suggest that apoptosis might contribute to cell death in isolated and banked primary hepatocytes.

Animals↗

Significance of the biopsy site of the latissimus dorsi muscle for fiber typing.

The use of the latissimus dorsi muscle for cardiomyoplasty requires accurate assessment of the outcome of methods used to convert fast fibers to slow fibers. A knowledge of the normal distribution pattern of slow fibers within the latissimus dorsi is necessary for this endeavor. Fresh latissimus dorsi and teres major muscle tissues from seven pigs, one rabbit, two sheep, one monkey, and four dogs were studied with myosin adenosine triphosphatase staining. Fiber counts were made visually. With the exception of the rabbit, the distribution patterns were similar for all species: (1) intersegmentally--the number of slow fibers decreased steadily from the teres major to the anterior edge of the lateral segment; (2) intrasegmentally--slow fibers were more frequent in the deep layer than the superficial layer; and (3) intrasegmentally--the slow fibers tended to cluster in rosette formations around the neurovascular bundles. These patterns of distribution indicate the need for careful location of biopsies to ensure valid comparison of the amount of slow fibers in tissue before and after treatment.

Animals↗

Overexpression of human reticulon 3 (hRTN3) in astrocytoma.

Neuroendocrine-specific protein (NSP) reticulons (RTN) are endoplasmic reticulum-associated protein complexes, which are localized in the endoplasmic reticulum (ER) and identified as markers for neuroendocrine differentiation. At least 4 different RTN genes have been identified in mammals, but in most cases, the functions of the encoded proteins except mammalian RTN4-A and RTN4-B are still elusive. In the present study, the expression of human reticulon 3 (hRTN3) in a variety of tissues was investigated. Northern blotting hybridization revealed higher expression of hRTN3 in normal brain and some endocrine-related organs such as thyroid relative to other non-endocrine organs. Twelve surgical specimens meeting the histological criteria for astrocytoma grade II, III and IV were investigated by in situ hybridization and immunohistochemical analysis, which demonstrated the overexpression of hRTN3 in astrocytoma tumor cells, while in non-cancerous brain tissues hRTN3 was mainly expressed in neurons and almost no signals in glia cells could be detected. The differential expression of hRTN3 between astrocytoma and non-cancerous tissue may provide insight into the progress of astrocytoma.

Aged↗

Enzyme-linked immunosorbent assay for microcystins in blue-green algal blooms.

A direct competitive enzyme-linked immunosorbent assay (ELISA) for the freshwater blue-green algal toxin microcystin (MCYST) in algae and water was developed. The assay involves coating anti-MCYST-variant leucine-arginine (LR) antibody to the ELISA plate and the use of MCYST-LR-peroxidase as the enzyme marker. The linear portion of the standard curve for MCYST in phosphate buffer containing saline (PBS) was 0.5-10.0 ng/mL (25-500 pg/assay). The minimum detection level for MCYST-LR was 0.20 ng/mL (10 pg/assay). Contaminated water could be directly used in the ELISA. The overall analytical recoveries for MCYST-LR added to water at levels of 1-20 ng/mL was 83.4%. For analysis of cellular MCYST, the toxin was first extracted from the algae with 0.1M ammonium bicarbonate, diluted with PBS to less than 0.5 mg dried algae/mL (less than 5.0 mg wet weight/mL) and directly used in the ELISA. C-18 reverse-phase Sep-Pak cartridges effectively adsorbed MCYST from the toxin-containing solutions. The toxin could be recovered from the cartridge by eluting with 60% methanol. Using this approach, an algae extract that was relatively free of MCYST was prepared and was used in a recovery study. The overall analytical recovery of MCYST added to the algae extract in the range of 0.25-20 ppm was 83% with a coefficient of variation of 11.9%. The detection limit for MCYST in dried algae was about 0.25-0.5 microgram/g (0.25-0.5 ppm) lyophilized algae sample. This method was applied for the analysis of several naturally occurring algal blooms. Limited samples were also analyzed for MYCST by liquid chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, Liquid↗