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Z Qin

Publications and source records attributed to Z Qin.

At least 55 records · Page 3Linked to original sources
PubMed1998

Retroviral interleukin-7 gene transfer into human dendritic cells enhances T cell activation.

Tumor vaccination with dendritic cells (DC) presenting tumor antigens to T cells is a promising approach in immunotherapy. The aim of this study was to enhance T cell stimulatory ability of human DC by retroviral expression of the interleukin-7 (IL-7) gene. IL-7 has been shown to provide a potent costimulatory signal for the proliferation of T cells and the generation of cytotoxic T cells (CTL). DC were generated from human peripheral blood mononuclear cells (PBMC). DC were analyzed by light- and electron-microscopy, immunophenotype (CD1a+, CD14-, CD80+, CD86+, HLA-DR+) and functional assays. According to these criteria, 75-85% of the cells were DC. The cells did not produce measurable amounts of IL-7 spontaneously nor did they express the IL-7 receptor. A retroviral IL-7 expression vector was constructed. Retroviral infection was performed with either the LXSN-hIL-7 vector of its variant LXSN. Using the LXSN-hIL-7 vector, IL-7 production of 2296 pg/10(6) cells/24 h could be achieved on average. Transduction of DC was confirmed by RT-PCR in a CD1a-enriched cell fraction. Transduction efficiency by a control virus coding for beta-galactosidase was about 30%. In autologous mixed lymphocyte reaction (MLR), IL-7 transduced DC augmented T cell proliferation by a factor of two compared with unmodified or mock-transfected DC, and in allogeneic MLR there was a 2.7-fold increase in T cell proliferation. The increase in T cell proliferation could be correlated to IL-7 secretion by DC. Dendritic cells that have been simultaneously peptide-loaded and gene-modified to secrete IL-7 are a potential tool to amplify activation of tumor-specific T cells.

Cells, Cultured↗
PubMed1998

Replication at the telomeres of the Streptomyces linear plasmid pSLA2.

The Streptomyces linear plasmid pSLA2 initiates DNA replication bidirectionally towards its telomeres from a site located near the centre of the molecule; at the telomeres, the recessed ends of lagging strands are filled in by non-displacing DNA synthesis. Here, we report experiments that test three proposed mechanisms for lagging-strand fill-in. We present data inconsistent with recombinational or terminal hairpin models for the formation of full-length duplex pSLA2 DNA. Instead, we find that deletions in short, distantly separated homologous palindromes in the leading-strand 3' overhang prevent propagation of linear pSLA2 DNA, implicating a mechanism of palindrome-mediated leading-strand fold-back in telomere replication. We further show that circularized pSLA2 DNA molecules are opened in vivo precisely at the terminal nucleotides of telomeres, generating functional linear replicons containing native telomeres covalently bound to a protein at their 5' DNA termini. Together, our results support a model in which pairing of multiple widely separated pSLA2 palindromes anchors the 3' end of the leading-strand overhang to a site near the overhang's base -- providing a recognition site for terminal-protein-primed DNA synthesis and subsequent endonucleolytic processing. Thus, the replication of Streptomyces plasmid telomeres may have features in common with the mechanism proposed for telomere replication in autonomous parvoviruses.

Base Sequence↗
PubMed1998

The Gfi-1B proto-oncoprotein represses p21WAF1 and inhibits myeloid cell differentiation.

Gfi-1 is a cellular proto-oncogene that was identified as a target of provirus integration in T-cell lymphoma lines selected for interleukin-2 (IL-2) independence in culture and in primary retrovirus-induced lymphomas. Gfi-1 encodes a zinc finger protein that functions as a transcriptional repressor. Here we show that Gfi-1B, a Gfi-1 related gene expressed in bone marrow and spleen, also encodes a transcriptional repressor. IL-6-induced G1 arrest and differentiation of the myelomonocytic cell line M1 were linked to the downregulation of Gfi-1B and the parallel induction of the cyclin-dependent kinase inhibitor p21WAF1. Experiments addressing the potential mechanism of the apparent coordinate regulation of these genes revealed that Gfi-1B represses p21WAF1 directly by binding to a high-affinity site at -1518 to -1530 in the p21WAF1 promoter. Forced expression of Gfi-1B, but not of Gfi-1B deletion mutants lacking the repressor domain, blocked the IL-6-mediated induction of p21WAF1 and inhibited G1 arrest and differentiation. We conclude that Gfi-1B is a direct repressor of the p21WAF1 promoter, the first such repressor identified to date, and that sustained expression of Gfi-1B blocks IL-6-induced G1 arrest and differentiation of M1 cells perhaps because it prevents p21WAF1 induction by IL-6.

3T3 Cells↗
PubMed1998

A review of therapeutic potentials in ischemic stroke.

Stroke is one of the leading causes of death in the world. There are as yet no effective treatments for the ischemic cerebral lesion itself. Nevertheless, five potential therapeutic objectives can be identified. For cerebral infarction, the best treatment is prevention, including targeted preventive treatments for specific subsets of patients or individuals with different risk factors. Incidence rates and mortality rates of stroke have been successfully reduced in certain developed countries by adoption of a public health approach to the prevention and control of risk factors. To rescue the still viable but injured nerve cells, within the ischemic penumbra, effective therapy should be begun at the earliest possible time. Measures to halt or reverse programmed cell death, to enhance the intrinsic autoprotective and repair mechanisms, are under active study. The existence of down-regulated brain regions, where normal nerve cells have far less activities to perform due to interruption of information exchange with the infarct area, and the possibility to reactivate them are worthy of attention.

Apoptosis↗
PubMed1998

Reduced immunoreactivity to calcium-binding proteins in Purkinje cells precedes onset of ataxia in spinocerebellar ataxia-1 transgenic mice.

Earlier we have shown alterations in immunoreactivity (IR) to the calcium-binding proteins parvalbumin (PV) and calbindin D-28k (CaB) in surviving Purkinje cells of patients with spinocerebellar ataxia-1 (SCA-1). In the present study we determined PV and CaB expression (by immunohistochemical and immunoblot analyses) in Purkinje cells of transgenic mice (TM) expressing the human SCA-1 gene with an expanded (line B05) and normal (line A02) CAG tract, as well as in age-matched nontransgenic mice (nTM). Heterozygotes in the B05 line develop progressive ataxia beginning around 12 weeks of age. A02 animals are phenotypically indistinguishable from wild-type (nontransgenic) animals. In the cerebella of 8-, 9-, and 12-week-old TM-B05 there was a progressive decrease in PV IR in Purkinje cells compared with nTM and TM-A02. Parvalbumin immunostaining in interneurons was well preserved in all groups. A progressive decrease was also observed in CaB IR in Purkinje cells of 8-, 9-, and 12-week-old TM-B05. Cerebellar Purkinje cells of 6-week-old TM-B05, which exhibit no ataxia and even lack demonstrable Purkinje cell loss, also revealed reduction in PV IR. This change was matched by a significant decrease in the amount of cerebellar PV in 6-week-old TM-B05 as determined by Western blot analysis. Calbindin D-28K immunohistochemistry did not detect any marked changes in CaB IR within Purkinje cells at 4 weeks. However, at 6 weeks immunostaining and immunoblot analysis revealed a significant decrease in CaB in TM-B05 compared with controls. These data suggest that decreased levels of calcium-binding proteins in Purkinje cells in SCA-1 transgenic mice may cause alteration in Ca2+ homeostasis.

Alleles↗
PubMed1998

The research of myelinization of normal fetal brain with magnetic resonance imaging.

OBJECTIVE: To investigate the growth and development of myelin of sheath fetal brain. METHODS: Forty-four cases of pregnant women were imaged with magnetic resonance (MR) at 0.35 T (tesla). The signal changes of the main structures of fetal brain were analysed. RESULTS: The signal intensity of cerebral (except basal ganglia) and cerebellar matter was hypo-signal on the T1WI (T1 weighted spin-echo image), iso-signal of the PDWI (Proton density weighted image) and hyper-signal on the T2WI (T2 weighted spin-echo image). As to the brain stem and basal ganglia, their signal intensities showed difference in different gestational weeks on T1WI. The intensities were of slight hypo-signal before and iso-signal after the 29th week. However, their signal intensities on PDWI and T2WI were the same as those of the cerebral and cerebellar matter. CONCLUSIONS: There was no myelinization of fetal cerebral (except basal ganglia) and cerebellar matter during pregnant period. The myelin sheath was formed in the brain stem and basal ganglia after 29 gestational weeks. The process of myelinization began from brain stem to basal ganglia.

Adult↗
PubMed1998

[A study of the expression of c-myc onoprotein in laryngeal cancer and different distant adjacent mucosa].

Using citric-LSAB-microwave immunohistochemical technique, the expression of c-myc was studied in different regions of larynx including laryngeal squamous cell carcinoma (LSCC), border area, adjacent mucosa which was 0.5, 1.0, 1.5 and 2.0 cm away from cancer 30 cases and four cases of normal laryngeal mucosa. The results showed that over-expression of c-myc in LSCC was found in 29 of 30 (96.7%), which was higher than that in normal laryngeal mucosa (P < 0.01). A significant different expression of c-myc can be seen at the regions of 2.0 and 1.5 cm distant from the tumor (P < 0.05). The expression of c-myc increased as tissue progressed in sequence from normal mucosa, adjacent mucosa to carcinoma. The c-myc expression did not correlate with site of tumor, stage and histological grade (P > 0.05). The results indicate that over-expression of c-myc is involved in genesis of LSCC, and may be an early event in the development of human squamous-cell carcinoma of the larynx. The tissue adjacent to the tumor may have a potential malignancy.

Adult↗
PubMed1998

[The treatment of rat fulminant hepatic failure by auxiliary partial heterotopic liver transplantation: experimental study].

OBJECTIVE: To confirm the effect of auxiliary partial heterotopic liver transplantation (APHLT) in the treatment of fulminant hepatic failure (FHF). METHOD: On 30 rat models of FHF, 62% of partial liver grafts were implanted below the host residual liver with 28 successful operations. The survival rate, biochemical test for liver function, (99m)Tc-HIDA liver scintigraphy and pathological changes of the grafts and host livers were studied. RESULT: The survival rate in 48 hours was 71.4% compared with 0% in 15 FHF animals. 14 days after the operation, the host liver regenerated obviously and the liver function recovered while the graft shrank gradually. 30 days later, the graft became fibrosis completely. CONCLUSION: Depending on the temporary function support of the graft, the native residual liver could regenerate and restore its function while the graft tended to atrophy.

Animals↗
PubMed1997

Decreased conformational stability of the sarcoplasmic reticulum Ca-ATPase in aged skeletal muscle.

Sarcoplasmic reticulum (SR) membranes purified from young adult (4-6 months) and aged (26-28 months) Fischer 344 male rat skeletal muscle were compared with respect to the functional and structural properties of the Ca-ATPase and its associated lipids. While we find no age-related alterations in (1) expression levels of Ca-ATPase protein, and (2) calcium transport and ATPase activities, the Ca-ATPase isolated from aged muscle exhibits more rapid inactivation during mild (37 degrees C) heat treatment relative to that from young muscle. Saturation-transfer EPR measurements of maleimide spin-labeled Ca-ATPase and parallel measurements of fatty acyl chain dynamics demonstrate that, accompanying heat inactivation, the Ca-ATPase from aged skeletal muscle more readily undergoes self-association to form inactive oligomeric species without initial age-related differences in association state of the protein. Neither age nor heat inactivation results in differences in acyl chain dynamics of the bilayer including those lipids at the lipid-protein interface. Initial rates of tryptic digestion associated with the Ca-ATPase in SR isolated from aged muscle are 16(+/- 2)% higher relative to that from young muscle. indicating more solvent exposure of a portion of the cytoplasmic domain. During heat inactivation these structural differences are amplified as a result of immediate and rapid further unfolding of the Ca-ATPase isolated from aged muscle relative to the delayed unfolding of the Ca-ATPase isolated from young muscle. Thus age-related alterations in the solvent exposure of cytoplasmic peptides of the Ca-ATPase are likely to be critical to the loss of conformational and functional stability.

Aging↗
PubMed1997

Down-regulation of the expression and function of the transporter associated with antigen processing in murine tumor cell lines expressing IL-10.

The MHC class I molecules present antigenic peptides to CTL. The peptides are delivered to the secretory pathway by TAP, which is formed by the association of MHC-encoded TAP1 and TAP2 gene products. Tumor cells incubated or transfected with IL-10 had decreased but peptide-inducible expression of MHC class I, decreased sensitivity to MHC class I-restricted CTL, and increased NK sensitivity. We here demonstrate that IL-10 expression in the murine lymphoma RMA inhibits the TAP-dependent translocation of peptides to the endoplasmic reticulum, resulting in accumulation of immature MHC class I molecules in the endoplasmic reticulum and subsequently low expression of cell surface MHC class I molecules. This finding is explained by a down-regulation of expression of TAP1 and TAP2, observed in IL-10-transfected RMA cells as well as in IL-10-transfected P815 mastocytoma cells. In the J558L plasmacytoma cell line, constitutively expressing high levels of IL-10, increased TAP-dependent translocation of peptides and expression of cell surface MHC class I could be induced by IL-10 antisense expression. IL-10 is the first example to demonstrate that a cytokine can decrease the expression and function of the TAP1/2 molecular complex and, in more general terms, the first example of a cytokine with an inhibitory effect on MHC class I-mediated Ag presentation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Experimental polyneuropathy produced in guinea-pigs immunized against sulfatide.

Antibodies to sulfatide are associated with polyneuropathy. To investigate the role of anti-sulfatide antibodies in this neurological disorder, guinea-pigs were immunized with sulfatide, and their behavior, serology and pathology were compared with animals injected with simple Freund's adjuvant. Eleven of 13 guinea-pigs that developed raised serum anti-sulfatide antibodies after five injections of sulfatide showed definite motor weakness. Demyelination of peripheral nerves and immunoglobulin deposits at peripheral nerve myelin sheath were found in symptomatic animals only. Functional impairment of the animals was significantly correlated with serum anti-sulfatide IgG levels and pathological findings in nerve fiber studies. Control animals and animals that received 1-3 injections of sulfatide were behaviorally and pathologically normal.

Animals↗
PubMed1997

Interleukin-10 prevents dendritic cell accumulation and vaccination with granulocyte-macrophage colony-stimulating factor gene-modified tumor cells.

A wide variety of human tumors express IL-10 for reasons poorly understood. We have analyzed the effect of spontaneous IL-10 expression by a mouse tumor (J558L) on its immunoparalyzing effect. Because "cross-priming" of T cells by host Ag-presenting cells for MHC class I-restricted tumor Ags is a major pathway for induction of tumor immunity and that is enhanced by granulocyte-macrophage (GM) CSF, we expressed this cytokine in J558L cells. GM-CSF-secreting cells were not effective when used for immunization against challenge with the parental tumor. Inhibition of IL-10 expression through an IL-10 antisense retrovirus restored the vaccine efficacy of GM-CSF-producing J558L cells, demonstrating a direct role of IL-10 in paralyzing the GM-CSF-induced antitumor immune response. Since the tumor used for challenge produced IL-10, we conclude that IL-10 interfered primarily with the initiation but not the effector phase of the immune response. Immunohistochemical analysis of the vaccine site showed a GM-CSF-induced accumulation of dendritic cells (DC) (MHC class II+ and DEC-205+) in the absence of IL-10. In the presence of IL-10, DC accumulation was completely inhibited. Together, our results demonstrate an antagonistic effect of IL-10 with respect to GM-CSF-induced DC accumulation and tumor immunity and suggest a new mechanism by which tumors escape immune recognition: namely by preventing APC from obtaining access to tumor Ags.

Animals↗
PubMed1997

Morphological characteristics and clinical significance of nerve distribution in pancreatic cancers.

Macroscopic and immunohistochemical observations were made to clarify the innervation of normal pancreatic tissues, and the clinicopathological and electron-microscopic findings of 33 cases of pancreatic cancer were obtained. The results showed that the innervation of both the head and the body of the pancreas mainly consisted of nerve fibers separated from the right celiac neuroganglion and the right half of the superior mesenteric arterial plexus. The pancreas was full of nerve fibers ending at acinar lobules, among which the adrenergic nerves commonly control the walls of blood vessels. Pancreatic cancer tends to be accompanied by invasion and metastasis along intra or extra-pancreatic nerves, and we found that the positive rates for invasion and metastasis were 73.33% and 60.00%, respectively. The follow-up study revealed that the nerve-invasion group had worse prognosis than the non-invasion group (P < 0.05). The approaches of the invasions of the nerves were as follows: (1) through the vessels of the perineurium; (2) through the perineurium; and (3) through the synaptic membrane of nerve endings. The invasion were a continuous process, often resulting in the destruction or even the disappearance of the normal structure of the nerve fibers. The above results suggest that there are plentiful vegetative nerves inside or outside the pancreas and that pancreatic cancers have a tendency of invading and metastasizing along or around nerves.

Adult↗
PubMed1997

[Study on HPV infection and p53 protein expression in laryngeal carcinoma].

UNLABELLED: In order to evaluate the role of human papillomavirus (HPV) infection and p53 protein expression in laryngeal squamous cell carcinoma (LSCC), the in situ hybridization and the labelled streptavidin biotin (LSAB) immunohistochemical method were used to detect the presence of HPV genomes 6B, 11, 16, 18 and expression of p53 protein respectively in 44 specimens of LSCC. And 16 specimens of laryngeal polyp were selected as controls. RESULTS: 1. HPV genomes 16/18 were detected in 19 (43.2%) of 44 LSCCs and in 2 (12.5%) of 16 laryngeal polyps (P < 0.05). 2.25 (56.9%) of 44 specimens of LSCC were p53 protein positive whereas the laryngeal polyps were all p53 negative. 3. 12 (63.2%) of 19 HPV 16/18 DNA-positive specimens of LSCC showed p53 protein expression and 12 (48%) of 25 p53 protein positive specimens of LSCC showed HPV 16/18 infection. CONCLUSION: Expression of p53 protein and infection of HPV 16, 18 may play a role in carcinogenesis of LSCC, respectively or simultaneously.

Adult↗
PubMed1997

Extremely low awareness of AIDS, sexually transmitted diseases and condoms among Dai ethnic villagers in Yunnan province, China.

OBJECTIVE: To assess the awareness of AIDS, other sexually transmitted diseases (STDs), condoms, sources of health information and HIV-related societal risks among Dai villagers in southern Yunnan Province, China. SUBJECTS AND METHODS: In November-December 1994, a cross-sectional descriptive study, comprising a questionnaire-based survey and focus group discussions, was conducted in three Dai villages in Mengla county; a total of 177 Dai villagers were interviewed in the survey and eight focus group discussions were held. Ethnographic observations provided a composite picture of HIV risks in the area. RESULTS: Only 18% of respondents had heard of AIDS, and only 25 and 28%, respectively, had heard of STDs or condoms. Furthermore, among these more aware groups, the level of knowledge was low and misconceptions were common. An ability to understand the official language (Mandarin) was the most important predictor of awareness of AIDS, other STDs or condoms. The sources of information in the three Dai villages sampled included TV, videos, radio and magazines, but only TV and videos had a large audience. Even so, these media were mostly in Mandarin and were not used in AIDS education. Travel outside of China was frequent; most villagers (77%) had traveled to Laos and 9% had traveled to Thailand. Societal risks of HIV transmission, such as an increasing incidence of STDs and an active sex industry, were observed in this area. CONCLUSIONS: Dai villagers in southern Yunnan Province had an extremely low awareness and knowledge of AIDS, other STDs and condoms. Given the high mobility of ethnic villagers to neighboring countries in Southeast Asia and the societal risks of HIV transmission in this area, there is an urgent need to provide accessible education about AIDS and other STDs. Suggestions regarding such health education and the implications of HIV policy-making are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Defining protein-protein interactions using site-directed spin-labeling: the binding of protein kinase C substrates to calmodulin.

EPR spectroscopy was used to examine protein-protein interactions between calmodulin and spin-labeled peptides based on the protein kinase C substrate domains of the myristoylated alanine rich C kinase substrate (MARCKS) and neuromodulin. When bound to calmodulin, the C- and N-terminal ends of a 25 residue MARCKS derived peptide exhibited large amplitude motion on the nanosecond time scale and were accessible to paramagnetic agents in aqueous solution. However, residues 5-23 were highly protected and in contact with side chains from calmodulin. These data are consistent with an alpha-helical configuration for this segment of MARCKS and with structures that have been obtained for other calmodulin-substrate complexes. For the 17 residue neuromodulin derived peptide, which is Ca2+ independent in its binding to calmodulin, oxygen collision rates demonstrate that one helical face of this peptide interacts strongly with calmodulin. The data are consistent with an interaction of this face specifically with the C-terminal lobe of calmodulin, where this lobe is either in an "open" or "semiopen" configuration. The EPR data also indicate that the N-terminal lobe of calmodulin is in contact with the peptide, but that this lobe is not as strongly associated with the peptide target. Overall, the binding pocket for neuromodulin appears to be less compact and more dynamic than that formed by MARCKS. This behavior has not previously been seen for calmodulin substrates, and it may play a role in the Ca2+ independent binding of this class of substrates. This work demonstrates the utility of EPR spectroscopy to define protein-protein interactions; in addition, oxygen collision frequencies obtained at buried sites appear to provide information on the conformational dynamics of proteins.

Amino Acid Sequence↗