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Biomedical subjects

Y Zeng

Publications and source records attributed to Y Zeng.

At least 181 records · Page 10Linked to original sources

Serological survey of nasopharyngeal carcinoma in 21 cities of south China.

This paper reports the results of serological survey of 318,912 persons for nasopharyngeal carcinoma (NPC) in 21 cities and counties of south China. There were 8,441 persons with positive VCA-IgA antibody (single item positive) of EB virus (EBV), with a rate of 2.65%. In these VCA-IgA positive persons, 287 persons also had positive EA-IgA (double items positive) of EBV. The overall positive rate was 0.09%. 100 cases of NPC were found and 87 of them (87.0%) were in early stage. NPC found in the group with single item positive accounts for 1.19%, but the rate in the group with double items positive was 19.16% (55 cases). In NPC patients with double items positive, 49 cases were in early stage (89.1%). In 100 cases of NPC found, 45 cases appeared with negative EA-IgA, only with positive VCA-IgA, which indicated that for diagnosis of NPC, sensitivity of EA-IgA was lower than that of VCA-IgA, but its specificity was higher. Therefore, both can increase the detecting rate and early diagnosis rate of NPC. The age of people checked varied with different antibody positive rate and NPC detecting rate. The three items showed a positive correlation. The results are compatible with those of the prospective study for NPC in Wuzhou City, Guangxi, China. The method for NPC serological diagnosis can be extended and applied to raise the NPC detecting rate and early diagnosis rate at secondary prevention. And, it is further proved that there is a close relationship between NPC and EBV.

Adult↗

Development of a polymer-enzyme immunoassay method and its application.

Both poly(N-isopropylacrylamide) and poly(N-isopropylacrylamide)-antibody (PINP-Ab)-labelled enzyme adhered quickly and tightly to cellulose acetate/nitrate membrane either below (less efficiently) or above (more efficiently) the lower critical solution temperature, and the retention of PINP-Ab on the membrane increased over 30-fold when compared with the unconjugated Ab. These characteristics were used to develop a novel polymer-enzyme-linked immunoassay method: homogeneous antigen-antibody immune-complexation reaction and a heterogeneous separation process. By using a simple horseradish-peroxidase-labelled antibody as a probe, we applied this method to the detection of human serum hepatitis B surface antigen (HBsAg). This immunoassay system can detect as little as 1 ng/ml of HBsAg. The advantages of this method are: (a) fast homogeneous immune complexation; (b) a rapid heterogeneous separation process; (c) high sensitivity; and (d) low non-specific background.

Acrylic Resins↗

[Molecular diagnosis of Huntington's disease: an analysis of two large families].

At present molecular techniques comprise a main resource in the early accurate diagnosis for Huntington's disease. We describe the molecular diagnosis for 8 HD patients and 39 risky family members in two large HD pedigrees by using G8 RFLP linkage analysis as well as direct detection of the expanded (CAG) repeat in IT15 gene with the nested PCR denaturing polyacrylamide gel electrophoretic autoradiography and direct DNA sequencing. The results showed that the normal IT15 alleles contained 13 to 26 CAG repeat but major in 16, while all the HD alleles had over 40 copies of (CAG)n. There was no overlap between the normal and affected alleles. The presymptomatic diagnosis of 39 family members at risk for HD disclosed that 11 subjects carried the affected alleles. All these results indicated that the unstable mutations in IT15 gene were responsible for HD in the Chinese. They also provide valuable data for HD molecular diagnosis, genetic counselling and genetic health.

Adolescent↗

[Construction of a retroviral vector carrying human growth hormone gene and its introduction and expression in 3T3 and ES cells].

In order to study the expression of growth hormone gene in heterologous cells, the retroviral vector pINS was used to construct the recombinant plasmid carrying the human growth hormone gene (hGH), and then it was introduced into mouse fibroblast cell line 3T3 and mouse embryonic stem cell line CCE. Levels of accumulation of hGH secreted into medium was quantified by a radioimmunoassay. Expression level of hGH gene varied considerably from one clone to another. Several 3T3 clones expressing hGH gene at high level were obtained, such as GHSNC 20, in which hGH concentration in medium was 3784ng/ml, Integration of exogenous gene was stable. Southern blot result showed that such kind of difference was not related to the number of integrated copies of the foreign gene. The expression of ES clones transfected with pINS-GH was undetectable, and integration of the foreign gene was unstable. Southern blot result showed that hGH gene really integrated into the cellular genome, and no rearrangement of foreign gene is found at present.

3T3 Cells↗

Epidemiology of anti-human T-cell leukemia virus type I antibody and characteristics of adult T-cell leukemia in China.

We analyzed the data from seroepidemiologic survey of anti-HTLV-I serum antibody (HTLV-1 Ab) and 16 adult cases of T-cell leukemia (ATL) in China (1984-1994). The results showed that the positive rate of HTLV-I Ab of the population of China was 0.54%, the birth or residence places of HTLV-I carriers and all the patients with ATL were mainly distributed in the coastal provinces and the northeast China, and a small endemic area of HTLV-I and ATl was found in Fujian Province (HTLV-I Ab positive rate, 2.1%). The HTLV-I in China may be transmitted from Japan or originated from China. The clinical characteristics of the cases included onset in adulthood; frequent skin lesions, lymphadenopathy and hepatosplenomegaly; no mediastinal mass; the ATL cells from peripheral blood with polymorphism nuclei and mature T cell immunophenotype HTLV-IAb positive in most of the cases tested (5/8); mostly acute type; with a median survival period of 3.5 months.

Adult↗

Molecular cloning of cDNA for double-stranded RNA adenosine deaminase, a candidate enzyme for nuclear RNA editing.

We have cloned human cDNA encoding double-stranded RNA adenosine deaminase (DRADA). DRADA is a ubiquitous nuclear enzyme that converts multiple adenosines to inosines in double-helical RNA substrates without apparent sequence specificity. The A --> I conversion activity of the protein encoded by the cloned cDNA was confirmed by recombinant expression in insect cells. Use of the cloned DNA as a molecular probe documented sequence conservation across mammals and detected a single transcript of 7 kb in RNA of all human tissues analyzed. The deduced primary structure of human DRADA revealed a bipartite nuclear localization signal, three repeats of a double-stranded RNA binding motif, and the presence of sequences conserved in the catalytic center of other deaminases, including a cytidine deaminase involved in the RNA editing of apolipoprotein B. These structural properties are consistent with the enzymatic signature of DRADA, and strengthen the hypothesis that DRADA carries out the RNA editing of transcripts encoding glutamate-gated ion channels in brain.

Adenosine Deaminase↗

Inhibition of transplant rejection by pretreatment of xenogeneic pancreatic islet cells with anti-ICAM-1 antibodies.

Cognate recognition of antigen-presenting cells by antigen-specific T cells is critically dependent on non-cognate adhesive interactions. For instance, several studies have shown that in vivo anti-LFA-1 plus anti-ICAM-1 mAb treatment results in prolongation of allograft survival. We have developed a xenogeneic islet transplant model to investigate the role of various adhesion interactions in the xenogeneic response and study the effect of pretreating donor tissue with immunosuppressive drugs. Pancreatic islet cells were pretreated in vitro with anti-human ICAM-1 mAb, transplanted under the renal capsule of diabetic B6 mice in the absence of systemic immunosuppression and examined for long-term xenograft acceptance. The survival of human islets pretreated with anti-human ICAM-1 was significantly prolonged (MST = 53 days, with 40% of grafts surviving > 100 days). In contrast, the survival of human islets pretreated with the control antibody was similar to those of nontreated islets (MST = 7 days). A massive lymphocyte infiltrate into control xenografts was observed at 5 days post-transplant. In contrast, a lymphocyte infiltrate did not appear in the anti-ICAM-1-treated islets for at least 11 days. Only mAbs specific for the LFA-1 binding epitope of ICAM-1 were found to inhibit a mixed islet/lymphocyte reaction in vitro and block graft rejection in vivo. However, graft prolongation is not accompanied by systemic tolerance. Mice transplanted simultaneously with human islet cells treated with control Ig (left kidney) or anti-ICAM-1 (right kidney) rejected the control islets but not anti-ICAM-1-treated islets. These results suggest that the LFA-1/ICAM-1 interaction is a critical component for xenograft rejection and, more important, that pretreatment of islet tissue with anti-adhesion molecule antibodies can profoundly alter graft recognition and rejection in the absence of any systemic drug therapy. However, graft prolongation is not accompanied by systemic tolerance induction.

Animals↗

The correlation between donor characteristics and the success of human islet isolation.

Clinical islet allotransplantation is dependent on the ability to achieve a high yield and purity of islets isolated from human cadaver pancreas donors. The aim of this study was to determine the factors influencing the pancreas prior to islet isolation that may alter yield and purity. The results of 50 consecutive islet isolations from cadaver donor human pancreati at the University of Chicago Medical Center from December 1991 to April 1993 were analyzed. All pancreati were first offered for whole pancreas transplantation before being considered for islet isolation. Human pancreatic islet isolation was accomplished by a modified automated method. Some islet isolations resulted in a high islet yield but low islet purity. Other resulted in well-purified islets, but a low yield. Arbitrarily, successful islet isolation is defined as that yielding over 250,000 islet equivalents (EQN) with a purity of at least 80%. The success rate of human pancreatic islet isolation was 70%. The mean final islet yield obtained from these 50 pancreati was 300,000 +/- 131,000 islet EQN. The mean purity of the final preparation was 73% +/- 25%. By univariate analysis, five factors were found to affect significantly the yield, purity, or overall success rate of islet isolation: organ cold ischemic time, donor age, donor plasma glucose levels, donor body weight, and cause of donor death. Even when islet isolation was successful, the function of islets from hyperglycemic and older donors appear to be impaired both in vitro and in vivo. These results suggest that islet yield and purity are affected by multiple donor-related factors. Even when adequate yield and purity are obtained, islet function is also dependent on donor variables.

Adolescent↗

Immunoglobulin signal transduction guides the specificity of B cell-T cell interactions and is blocked in tolerant self-reactive B cells.

The specificity of antibody (Ab) responses depends on focusing helper T (Th) lymphocyte signals to suitable B lymphocytes capable of binding foreign antigens (Ags), and away from nonspecific or self-reactive B cells. To investigate the molecular mechanisms that prevent the activation of self-reactive B lymphocytes, the activation requirements of B cells specific for the Ag hen egg lysozyme (HEL) obtained from immunoglobulin (Ig)-transgenic mice were compared with those of functionally tolerant B cells isolated from Ig-transgenic mice which also express soluble HEL. To eliminate the need for surface (s)Ig-mediated Ag uptake and presentation and allow the effects of sIg signaling to be studied in isolation, we assessed the ability of allogeneic T cells from bm12 strain mice to provide in vivo help to C57BL/6 strain-transgenic B cells. Interestingly, non-tolerant Ig-transgenic B cells required both allogeneic Th cells and binding of soluble HEL for efficient activation and Ab production. By contrast, tolerant self-reactive B cells from Ig/HEL double transgenic mice responded poorly to the same combination of allogeneic T cells and soluble HEL. The tolerant B cells were nevertheless normally responsive to stimulation with interleukin 4 and anti-CD40 Abs in vitro, suggesting that they retained the capacity to respond to mediators of T cell help. However, the tolerant B cells exhibited a proximal block in the sIg signaling pathway which prevented activation of receptor-associated tyrosine kinases in response to the binding of soluble HEL. The functional significance of this sIg signaling defect was confirmed by using a more potent membrane-bound form of HEL capable of triggering sIg signaling in tolerant B cells, which markedly restored their ability to collaborate with allogeneic Th cells and produce Ab. These findings indicate that Ag-specific B cells require two signals for mounting a T cell-dependent Ab response and identify regulation of sIg signaling as a mechanism for controlling self-reactive B cells.

Animals↗

A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses.

A new experimentally testable hypothesis is advanced for the mechanosensory transduction mechanism by which communicating osteocytes sense the very small in vivo strains in the calcified matrix components of bone. We propose that the osteocytes, although not responsive to substantial fluid pressures, can be stimulated by relatively small fluid shear stresses acting on the membranes of their osteocytic processes. Biot's porous media theory is used to relate the combined axial and bending loads applied to a whole bone to the flow past the osteocytic processes in their canaliculi. In this theory, the bone pores of interest are the proteoglycan filled fluid annuli that surround the osteocytic processes in the canaliculi. We show that previously predicted fluid pore pressure relaxation times were a hundred-fold too short for the lacunar-canalicular porosity because they neglected the fluid drag associated with proteoglycan matrix on the surface membrane of the osteocyte and its cell processes. The recent theory developed in Tsay and Weinbaum [J. Fluid Mech. 226, 125-148 (1991)] for flow through cross-linked fiber filled channels is used to model the flow through this proteoglycan matrix. The predicted pore relaxation time, 1-2 s, closely corresponds to the times measured by Salzstein and Pollack [J. Biomechanics 20, 271-280 (1987)]. Furthermore, using this model, the magnitude of the predicted fluid induced shear stresses, 8-30 dyn cm-2, is shown to be similar to the fluid shear stresses measured in osteoblasts and other cells in which an intracellular Ca2+ shear stress response had been observed. This model is also used, in conjunction with anatomical data and the pore fluid pressure relaxation time data, to show that the spacing between the fibers is approximately 7 nm. The result is consistent with the notion that the canalicular pore space is filled with glycosaminoglycans that are ordered by albumin according to the model of Michel [J. Physiol. 404, 1-29 (1988)]. The new hypothesis is also shown to be consistent with the experiments of McLeod et al. [J. Biomechanics (submitted)] which suggest that high-frequency low-amplitude postural strains can maintain and even increase bone mass.

Animals↗

Environmental and dietary risk factors for nasopharyngeal carcinoma: a case-control study in Zangwu County, Guangxi, China.

A case-control study was conducted on 88 incident cases of histologically confirmed undifferentiated nasopharyngeal carcinoma (NPC) in Zangwu County, China, and 176 age- sex- and neighbourhood-matched controls. The design of this study was defined after an anthropological survey on living habits in regions of high NPC incidence and the evidence of carcinogenic substances in some commonly consumed preserved foods. Subjects were interviewed regarding living conditions and diet in the year preceding the diagnosis of NPC and, with the help of their families, during childhood and weaning. After adjustment for a living conditions score to eliminate a confounding effect, an increased risk associated with consumption of salted fish during weaning and childhood was confirmed, especially for salted fish in rice porridge. The consumption of leafy vegetables was associated with a reduced risk for NPC, and consumption of melon seeds between 2 and 10 years of age with an increased risk. After multivariate analysis and adjustment according to the living conditions score, the consumption of salted fish in rice porridge before age 2 (OR = 3.8, P = 0.005), exposure to domestic woodfire (OR = 5.4, P = 0.01) and consumption of herbal tea (OR = 4.2, P = 0.02) were found to be independently related to the risk of NPC. The excess risk associated with the use of domestic wood fire increased if there were no windows in the house and with poor ventilation and cooking outside the house in a shack. As well as confirming the importance of the consumption of salted fish in childhood, this study has been the first to provide unequivocal evidence for two other factors implicated in increasing the risk of NPC in China, the adult consumption of traditional medicines (herbal tea) and exposure to domestic wood fumes.

Adult↗

Antigen-specific human monoclonal antibodies from mice engineered with human Ig heavy and light chain YACs.

We describe a strategy for producing human monoclonal antibodies in mice by introducing large segments of the human heavy and kappa light chain loci contained on yeast artificial chromosomes into the mouse germline. Such mice produce a diverse repertoire of human heavy and light chains, and upon immunization with tetanus toxin have been used to derive antigen-specific, fully human monoclonal antibodies. Breeding such animals with mice engineered by gene targeting to be deficient in mouse immunoglobulin (Ig) production has led to a mouse strain in which high levels of antibodies are produced, mostly comprised of both human heavy and light chains. These strains should provide insight into the adoptive human antibody response and permit the development of fully human monoclonal antibodies with therapeutic potential.

Adult↗

Purification and immunochemical properties of human Na,K-ATPase alpha subunits and formic acid-derived polypeptide fragments.

In this study, alpha (alpha) isoform proteins were purified from the partially purified Na,K-ATPase by SDS-PAGE and electroelution. Peptide mapping showed subtle biochemical differences between alpha subunit proteins of rat and human origin. The purified alpha proteins were treated with formic acid, the cleaved polypeptide fragments were separated by SDS-PAGE, the bands corresponding to 40, 50, and 60 kDa were excised, and the proteins were electroeluted. The purified 40, 50, and 60 kDa polypeptides were essentially homogeneous, and were used for preparation of polyclonal antibodies in rabbits. The antisera to alpha proteins (R alpha) and 60 & 40 kDa polypeptides (R60 & R40) were obtained and characterized by Western blotting. All three antisera were highly specific, since they cross-reacted with only the 100 kDa bands of the crude brainstem homogenates, of the axolemma, and of the cerebral cortex synaptosomes and microsomes. R alpha and R40 were successfully used for immunohistochemical staining of fibers in the white matter of the human brain frontal cortex. These antisera were not isoform-specific, they cross-reacted with 40, 50, and 60 kDa polypeptides as well as the three alpha bands.

Animals↗