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Biomedical subjects

Yong Zhu

Publications and source records attributed to Yong Zhu.

At least 19 recordsLinked to original sources

Ala394Thr polymorphism in the clock gene NPAS2: a circadian modifier for the risk of non-Hodgkin's lymphoma.

Circadian disruption is theorized to cause immune dysregulation, which is the only established risk factor for non-Hodgkin's lymphoma (NHL). Genes responsible for circadian rhythm are also involved in cancer-related biological pathways as potential tumor suppressors. However, no previous studies have examined associations between circadian genes and NHL risk. In this population-based case control study (n = 455 cases; 527 controls), we examined the only identified nonsynonymous polymorphism (Ala394Thr; rs2305160) in the largest circadian gene, neuronal PAS domain protein 2 (NPAS2), in order to examine its impact on NHL risk. Our results demonstrate a robust association of the variant Thr genotypes (Ala/Thr and Thr/Thr) with reduced risk of NHL (OR = 0.66, 95% CI: 0.51-0.85, p = 0.001), especially B-cell lymphoma (OR = 0.61, 95% CI: 0.47-0.80, p <or= 0.0001). These findings provide the first molecular epidemiologic evidence supporting a role of circadian genes in lymphomagenesis, which suggests that genetic variations in circadian genes might be a novel panel of promising biomarkers for NHL and warrants further investigation.

Aged↗

Preparation of Fe3O4-C18 nano-magnetic composite materials and their cleanup properties for organophosphorous pesticides.

Magnetic Fe3O4-C18 composite nanoparticles of approximately 5-10 nm in size were synthesized and characterized by IR spectroscopy, atomic absorption spectroscopy, X-ray diffraction, and transmission electron microscopy. The magnetic Fe3O4-C18 composite nanoparticles were applied for cleanup and enrichment of organophosphorous pesticides. Comparative studies were carried out between magnetic Fe3O4-C18 composite nanoparticles and common C18 materials. Residues of organophosphorous pesticides were determined by gas chromatography in combination with a nitrogen/phosphorus detector. The cleanup and enrichment properties of magnetic Fe3O4-C18 composite nanoparticles are comparable with those of common C18 materials for enrichment of organophosphorous pesticides, but the cleanup and enrichment are faster and easier to perform.

Chromatography, Gas↗

Family history of hematopoietic and non-hematopoietic malignancies and risk of non-Hodgkin lymphoma.

BACKGROUND: Family history of hematopoietic malignancies has been linked to the risk of non-Hodgkin lymphoma (NHL). The relationship between family history of specific hematopoietic and non-hematopoietic malignancies and the risk of NHL and by NHL subtypes are unclear. METHODS: We analyzed data from a population-based case-control study in Connecticut women. A total of 601 histologically confirmed NHL incident cases and 717 randomly selected controls were included in the study. Unconditional logistic regression was used to estimate the association between family cancer history and risk of NHL overall and by NHL subtypes. RESULTS: Compared to women who reported to have no family history of any malignancies in first-degree relatives, those who reported to have a family history of lymphoma (OR = 2.2, 95%CI: 1.1-4.5) or leukemia (OR = 2.5, 95%CI: 1.2-5.2) had an increased risk of NHL. The risk was higher among women who had a sibling with lymphoma or leukemia than those who had parents with lymphoma or leukemia. Several non-hematopoietic malignancies in first-degree relatives, including cancer of the lung (OR = 1.7, 95%CI: 1.1-2.6) in first-degree relatives, stomach (OR = 2.2, 95%CI: 0.8-5.9) and pancreas (OR = 2.6, 95%CI: 0.9-7.1) in parents, as well as liver (OR = 5.0, 95%CI: 1.0-24.6), breast (OR = 2.2, 95%CI: 1.3-3.9), cervix (OR = 7.5, 95%CI: 0.9-64.9), and ovary (OR = 3.5, 95%CI: 1.1-11.5) in siblings were also associated with an increased risk of NHL. CONCLUSIONS: The risk associated with a family history of malignancies in first degree-relatives appears to vary by type of first-degree relatives.

Case-Control Studies↗

The effects of the members of growth hormone family knockdown in zebrafish development.

Growth hormone (GH), prolactin (PRL), and somatolactin (SL) are members of GH/PRL superfamily. These hormones are involved in the regulation of an array of physiological processes, including growth, lactation, and osmoregulation. While recent evidence has shown the GH, PRL, and SL gene transcripts and protein products are expressed during early zebrafish development, their functions at this time of embryogenesis remain unknown. In the current study, antisense morpholino oligonucleotide (MO) inhibition of gh, prl, and sl gene translation was used to examine the effects of gene knockdown on hormone function in zebrafish development. We observed that PRL, SLalpha and SLbeta MO treatment all affected development. PRL MO-treated embryos showed defects in gas bladder inflation, reduced head and eye size, shorter body length and fewer melanophores than untreated controls, whereas SLalpha and SLbeta MO-treated embryos were only defective in gas bladder inflation, GH MO-inhibition of GH specific translation did not lead to any discernable morphological changes within 10 days post fertilization (dpf). The effects of PRL knockdown were further verified using a second PRL morpholino antisense and by a rescue experiment with in vitro transcribed prl mRNA containing 5 nucleotide mismatch within the PRL-MO binding region. These results provide the first evidence that members of the GH/PRL superfamily play a role in proper development of various structures including the head, eyes, melanophores and the gas bladder in zebrafish.

Air Sacs↗

Enhancement of endogenous defenses against ROS by supra-nutritional level of selenium is more safe and effective than antioxidant supplementation in reducing hypertensive target organ damage.

Hypertension-induced target organ damage (TOD), is one of the leading causes of morbidity and mortality. Reactive oxygen species (ROS) play an important role in the pathogenesis and development of hypertension. It has been suggested that hypertension-induced TOD is related to the level of oxidative stress, but is in part independent of the level of blood pressure. Therefore, in addition to anti-hypertensive drug therapy, novel strategies against ROS, will provide additional benefits to patient with hypertension. Vitamin E has long been supplemented as an effective antioxidant. However, the potential hazardous effects of vitamin E supplementation as antioxidant revealed by recent studies make its clinical and routine use prudent. Therefore, novel approaches capable of enhancing endogenous system to defend against ROS are required. Here, we propose that enhancement of intrinsic defenses against ROS by supra-nutritional level of selenium is more safe and effective than antioxidant supplementation in reducing hypertensive target organ damage, owing to its role in activating and constitution of native vital proteins and/or enzymes against oxidative stress, and the fact that scarcity of selenium can not be supplemented by normal food, and potentially extra benefits by supra-normal intake.

Antioxidants↗

Diversity in lectins enables immune recognition and differentiation of wide spectrum of pathogens.

Carbohydrate-binding lectins play essential roles as pattern recognition receptors in innate immunity in both vertebrates and invertebrates. The carcinolectins 5 (CL5a and CL5b, the CL5 isoforms of horseshoe crab, Carcinoscorpius rotundicauda, with apparent sizes of 36 and 40 kDa, respectively) are prominent plasma lectins that bind all representative microbes and pathogen-associated molecular pattern molecules. Different cDNA isoforms of both CL5a and CL5b were isolated, leading to our speculation on their functional divergence. Characterization of CL5 isoforms bound to microbial cell surfaces demonstrates the diversity of these lectins. The resolution patterns of the isoforms that associate with fungus differ from those that associate with bacteria, suggesting the unique roles these lectins play in the recognition and differentiation of microbes. We postulate that different populations of plasma lectins act in collaboration in frontline innate immune defense against disparate pathogens. The functional diversity of lectins in invertebrates appears to evolutionarily compensate for the lack of acquired immunity.

Amino Acid Sequence↗

Association of surfactant protein A polymorphisms with otitis media in infants at risk for asthma.

BACKGROUND: Otitis media is one of the most common infections of early childhood. Surfactant protein A functions as part of the innate immune response, which plays an important role in preventing infections early in life. This prospective study utilized a candidate gene approach to evaluate the association between polymorphisms in loci encoding SP-A and risk of otitis media during the first year of life among a cohort of infants at risk for developing asthma. METHODS: Between September 1996 and December 1998, women were invited to participate if they had at least one other child with physician-diagnosed asthma. Each mother was given a standardized questionnaire within 4 months of her infant's birth. Infant respiratory symptoms were collected during quarterly telephone interviews at 6, 9 and 12 months of age. Genotyping was done on 355 infants for whom whole blood and complete otitis media data were available. RESULTS: Polymorphisms at codons 19, 62, and 133 in SP-A1, and 223 in SP-A2 were associated with race/ethnicity. In logistic regression models incorporating estimates of uncertainty in haplotype assignment, the 6A4/1A5haplotype was protective for otitis media among white infants in our study population (OR 0.23; 95% CI 0.07,0.73). CONCLUSION: These results indicate that polymorphisms within SP-A loci may be associated with otitis media in white infants. Larger confirmatory studies in all ethnic groups are warranted.

Alleles↗

Polymorphisms in DNA repair genes and risk of non-Hodgkin lymphoma among women in Connecticut.

Several hereditary syndromes characterized by defective DNA repair are associated with high risk of non-Hodgkin lymphoma (NHL). To explore whether common polymorphisms in DNA repair genes affect risk of NHL in the general population, we evaluated the association between single nucleotide polymorphisms (SNPs) in DNA repair genes and risk of NHL in a population-based case-control study among women in Connecticut. A total of 518 NHL cases and 597 controls recruited into the study provided a biologic sample. Thirty-two SNPs in 18 genes involved in several DNA repair pathways were genotyped. Genotype data were analyzed by unconditional logistic regression adjusting for age and race. SNPs in four genes (ERCC5, ERCC2, WRN, and BRCA1) were associated with altered risk of NHL and diffuse large B-cell lymphoma (DLBCL), the major B cell subtype. In particular, ERCC5 Asp1104His was associated with increased risk of NHL overall (OR: 1.46; 95% CI: 1.13-1.88; P=0.004), DLBCL (OR: 1.44; 95% CI: 0.99-2.09; P=0.058), and also T cell lymphoma. WRN Cys1367Arg was associated with decreased risk of NHL overall (OR: 0.71; 95% CI: 0.56-0.91; P=0.007) and DLBCL (OR: 0.66; 95% CI: 0.45-0.95; P=0.024), as well as follicular and marginal zone lymphomas. Genetic polymorphisms in DNA repair genes, particularly ERCC5 and WRN, may play a role in the pathogenesis of NHL, especially for DLBCL. Further work is needed to extend these findings by carrying out extended haplotype analyses of these and related genes and to replicate the observations in other studies.

Adult↗

Improved preparation of class I HLA tetramers and their use in detecting CMV-specific CTL.

Different methods were used to prepare HLA tetramers and the yields of each method were compared. Our results indicate that preliminary refolding of the heavy chain (Hc) and light chain (beta 2m) yields more monomer than the typical conventional method with urea-solubilized Hc and beta 2m. We then used the corresponding tetramers to detect cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CTL). Increasing data suggest that the adoptive transfer of CMV-specific CTL constitutes an effective strategy against CMV infections. We designed a method that efficiently induces CMV-specific CTL to a higher frequency in vitro than is currently achieved. This method increased the percentage of CMV-specific CTL from below 1% to 20% of PBL, accounting for more than 40% of CD8+ T cells. Successful HLA tetramer preparation provides the basis for the subsequent detection of CMV-specific CTL in clinical applications.

Cytomegalovirus↗

Dynamic changes of apoptosis-inducing ligands and Th1/Th2 like subpopulations in Hantaan virus-induced hemorrhagic fever with renal syndrome.

The expression of the apoptosis-inducing ligands, TNF-alpha, FasL and TRAIL on peripheral blood mononuclear cells (PBMC) and the levels of their soluble form (TNF-alpha, sFasL and sTRAIL) in plasma from 40 hemorrhagic fever with renal syndrome (HFRS) patients as well as 26 healthy blood donors were determined by flow cytometry (FCM) analysis and sandwich ELISA, respectively. The status of Th1, Th2, Tc1 and Tc2 subsets in PBMC was evaluated by intracellular cytokine staining and FCM. Compared to controls, the expression of membrane bound FasL and TRAIL was up-regulated on surface of PBMC isolated from the HFRS patients, particularly on CD8+ T lymphocytes. The levels of TNF-alpha, sFasL and sTRAIL in plasma from the HFRS patients in the acute phase increase 4.7-fold, 6.0-fold and 1.8-fold, respectively, over those from the healthy donors. The percentage of Th1, Tc1 and Tc2 subsets in PBMC from the patients also increased significantly compared with those from healthy donors. These results indicate that dynamic changes occurred in both the membrane bound and soluble forms of apoptosis-inducing ligands (FasL, TRAIL and TNF-alpha) and proportions of Th1 and CTL in HFRS patients increased. Both factors may play an important role in the etiology of Hantaan virus infection in humans.

Adolescent↗

Generation of monoclonal antibodies to cancer/testis (CT) antigen CT10/MAGE-C2.

CT10/MAGE-C2 is a recently identified antigen that, typically of cancer/testis (CT) antigens, can be found in various malignant tumors and in normal adult testis. As with many other CT antigens, our knowledge is based mainly on mRNA expression data. In the present study, we describe the generation of mAbs to CT10/MAGE-C2 for the analysis of its protein expression. Newly generated clones were chosen based on their reactivity in ELISA, immunoblotting, and immunohistochemistry (IHC). Emphasis was put on the reactivity of newly generated reagents on formalin-fixed, paraffin-embedded tissue to ensure their applicability to archival material. Eventually we selected two clones, LX-CT10.5 and LX-CT10.9, that showed intense reactivity to CT10/MAGE-C2 protein and CT10/MAGE-C2 mRNA-positive cell lines, but no cross-reactivity with other CT antigens. Both mAbs show superior staining characteristics in IHC and are applicable to frozen and paraffin sections. In testis, CT10/MAGE-C2 displays the typical CT pattern with regard to staining of germ cells, which is intense during the early maturation stages. In tumors, we analyzed a limited number of cases displaying the typical heterogeneous CT expression pattern. Interestingly, immunoreactivity was seen solely in the nucleus: No staining was seen in the cytoplasm of tumor cells.

Animals↗

Cytokine polymorphisms in the Th1/Th2 pathway and susceptibility to non-Hodgkin lymphoma.

Studies have demonstrated that common polymorphisms in Th1 and Th2 cytokine genes can alter gene expression, modulate the balance between Th1/Th2 responsiveness, and influence susceptibility for autoimmune disorders, infectious diseases, and cancer. We analyzed one or more single nucleotide polymorphisms (SNPs) in 20 candidate Th1/Th2 genes in a population-based case-control study of non-Hodgkin lymphoma (NHL; n = 518 cases, 597 controls) among women in Connecticut. SNPs in critical genes, IL4, IL5, IL6, and IL10, were associated with risk for NHL and in some instances with a specific histologic subtype. Analysis of 4 SNPs in the IL10 promoter (-3575T>A, -1082A>G, -819C>T, and -592C>A) revealed that both the AGCC haplotype (odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.21-1.96, P < .001) and the TATA haplotype (OR = 1.37, 95% CI = 1.05-1.79, P = .02) were associated with increased risk for B-cell lymphomas. In contrast, the IL4-1098G allele was associated with increased risk of T-cell lymphomas (OR = 3.84; 95% CI = 1.79-8.22; P < .001). Further, the IL10 and IL4 SNP associations remained significant after adjusting for multiple comparisons. These results suggest that SNPs in Th2 cytokine genes may be associated with risk of NHL.

Adult↗

Occupational and leisure-time physical activity and risk of colon cancer by subsite.

OBJECTIVE: Studies of physical activity and colon cancer risk by anatomic site have provided inconsistent results. METHODS: We analyzed data from a population-based case-control study conducted in Iowa involving 685 colon cancer cases and 2434 control subjects. RESULTS: Among those who reported recreational activity more than twice per week, a 30% risk reduction of colon cancer was observed for all sites with a 40% risk reduction for cancer of the right colon. Occupational physical activity was also associated with a reduced risk of colon cancer. The risk was the lowest for those with both high occupational and recreational physical activity (odds ratio, 0.5; 95% confidence interval, 0.3-0.8). CONCLUSIONS: Increased physical activity was inversely associated with colon cancer risk. The inverse associations were stronger for the right than for the left colon.

Adult↗

Does "clock" matter in prostate cancer?

The ancient adaptation of a 24-hour circadian clock has profound effect on our daily biochemical, physiologic, and behavioral processes, including the monitoring of sex hormone levels. Although the disruption of the circadian cycle has been implicated in the etiology of hormone-related female breast cancer, few studies have been undertaken to determine if a link exists in the development of the most common cancer type among men whose etiology remains largely unknown: hormone-related prostate cancer. Here, we hypothesize that both altered-lighted environments and genetic variations in genes responsible for maintaining circadian rhythms may result in deregulation of clock-associated biological processes, such as androgen expression, and consequently influence an individual's risk of prostate cancer. There is also a potential for the interaction of genetic variants and exposures, such as evening shift work. Confirmation of this hypothesis will add to our understanding of the role of the circadian clock in prostate tumorigenesis and further facilitate the development of novel risk and prognostic biomarkers for prostate cancer.

Androgens↗

Proposal to create subspecies of Rickettsia sibirica and an emended description of Rickettsia sibirica.

The Rickettsia sibirica species is composed of isolates that are genotypically close but can be classified within two distinct serotypes, that is, R. sibirica sensu stricto and R. sibirica mongolitimonae (incorrectly named R. mongolotimonae). We investigated the possibility of classifying rickettsiae closely related to R. sibirica as R. sibirica subspecies, as proposed by the ad hoc Committee on Reconciliation of Approaches to Bacterial Systematics. For this, we first estimated the genotypic variability by using multilocus sequence typing (MLST), including the sequencing of five genes, and multispacer typing (MST) using three intergenic spacers, of five isolates and three tick amplicons of R. sibirica sensu stricto and six isolates of R. sibirica mongolotimonae. Then, we selected a representative of each MLST genotype and used mouse serotyping to estimate their degree of taxonomic relatedness. Among the 14 isolates or tick amplicons studied, 2 MLST genotypes were identified: (i) the R. sibirica sensu stricto type; and (ii) the R. sibirica mongolitimonae type. Representatives of the two MLST types were classified within three MST types and into two serotypes. Therefore, as isolates within the R. sibirica species are genotypically homogeneous but show MST genotypic, serotypic, and epidemio-clinical dissimilarities, we propose to modify the nomenclature of the R. sibirica species through the creation of subspecies. We propose the names R. sibirica subsp. sibirica subsp. nov. (type strain = 2-4-6, ATCC VR-541(T)), and R. sibirica subsp. mongolitimonae subsp. nov. (type strain = HA-91, ATCC VR-1526(T)). The description of R. sibirica is emended to accommodate the two subspecies.

Animals↗

Cell-surface expression, progestin binding, and rapid nongenomic signaling of zebrafish membrane progestin receptors alpha and beta in transfected cells.

Recently, a unique family of membrane progestin receptors (mPRalpha, mPRbeta, and mPRgamma) was identified, which may be responsible for mediating rapid, nongenomic actions of progestins in a variety of target tissues. In this study, the mPRalpha and mPRbeta isoforms from zebrafish were shown to be rapidly and specifically activated by the maturation-inducing steroid (MIS) of this species, 4-pregnen-17,20beta-diol-3-one (17,20beta-DHP). The zebrafish mPRalpha and a previously uncharacterized mPRbeta isoform were stably expressed in nuclear progesterone receptor-deficient mammalian breast cancer cells, MDA-MB-231. Expression and surface localization of the receptors were verified by flow cytometry, biotin surface labeling, and Western blotting. Plasma membrane proteins from mPRalpha- or mPRbeta-transfected cells showed high affinity (mPRalpha, K(d) 7 nM; mPRbeta, K(d) 12 nM), saturable, displaceable, single-binding sites specific for 17,20beta-DHP, whereas negligible specific 17,20beta-DHP binding was observed in nontransfected cells. Progestin treatment caused significant activation of mitogen-activated protein kinase (MAPK) within 5 min in cells transfected with either of the receptors as measured by western blotting and flow cytometry. The rank order of the potencies of several progestins in activating MAPK via mPRalpha and mPRbeta was the same (17,20beta-DHP>progesterone >4-pregnen-17,20beta,21-triol-3-one). Interestingly, the MIS in zebrafish, 17,20beta-DHP, was also the most potent inhibitor, among the progestins tested, of adenylyl cyclase activity in cells transfected with either of the receptors. This progestin significantly decreased cAMP levels in both mPRalpha- and mPRbeta-transfected cells in a dose-responsive and time-dependent manner. In addition, signaling of the zebrafish mPRalpha was blocked by pertussis toxin, implying activation of a G(i) protein, while sensitivity to pertussis or cholera toxin was not shown with mPRbeta-mediated signaling, possibly indicating that this receptor activates a different pertussis toxin-insensitive G protein. The results of this study suggest that zebrafish mPRalpha and mPRbeta signal similarly upon progestin binding resulting in rapid activation of MAPK and downregulation of adenylyl cyclase activity.

Animals↗

[Indications for colonoscopy examination and its disease distribution: a report of 5690 cases].

OBJECTIVE: To explore the indications for colonoscopy examination and the distribution of diagnostic diseases. METHOD: From Jan. 2000 to Dec. 2004, 5960 patients received colonoscopy examination in our colorectal center. The indications for colonoscopy examination and the distribution of its diagnostic diseases were analyzed. RESULTS: There were 3096 males and 2594 females,and the mean age was (52+/-15) years. The reasons for colonoscopy included hemafecia (26.9%), atypical abdominal pain (25.8%), diarrhea or increased frequency of stool (11.1%), anal tenesmus or discomfort (7.6%), constipation (7.0%),mucous or bloody purulent stool (3.0%), intra-rectal mass or abdominal mass on physical examination (0.9%), re- examination after colonoscopic polypectomy (10.9%), re-examination after operation for colorectal cancer(1.5%), simple health examination (2.2%). Colonoscope reached the cecum in 97.7% of the cases,and at least one disease was found in 2283 cases (40.1%). Among them,colorectal cancer accounted for 10.3%, colorectal polyps 19.6%, ulcerative colitis 4.3%, and Crohn's disease 0.5% respectively. CONCLUSION: The indications for colonoscopy are too strict to screen the early stage colorectal cancer. Colonoscopy should be performed in the cases with symptoms such as bloody stool, diarrhea, abdominal pain, constipation, or with colorectal polyps, after operation for colorectal cancer,or as members of hereditary colorectal cancer family.

Adolescent↗