Biomedical subjects

S Xiong

Publications and source records attributed to S Xiong.

At least 55 records · Page 3Linked to original sources

PubMed2000

[Factor XIIa-inhibited diluted thromboplastin time can reflect coagulation process].

OBJECTIVE: To establish a screening test that can reflect two stages of coagulation process. METHODS: With FXII a being blocked, the effects of various dilution of thromboplastin on clotting time were observed. FX a activity was determined by chromogenic assay. RESULTS: (1) At high concentration of thromboplastin, FXII a-inhibited diluted thromboplastin time (FXII ai DTT) of pooled normal plasma and FXI deficient plasma was very similar, but at low concentration, FXII ai DTT was in order of FVIII and FIX deficient plasma > FXI deficient plasma > pooled normal plasma. (2) FXI consumption by immunologic method induced FXII ai DTT of pooled normal plasma prolonged, and addition of FXI to FXI deficient plasma shortened FXII ai DTT. (3) Alpha-thrombin blocked by hirudin at different time (10 - 80 seconds) resulted in decreased FXa generation, and the earlier the block, the more the decrease. Under the same condition, the amount of FXa generation was in order of platelet-rich plasma > platelet-poor plasma > FXI deficient plasma. CONCLUSION: (1) Our data support the two-stage hypothesis and confirm the important role of FXI in the amplification stage. (2) FXII ai DTT as a screening test for coagulation process may be practicable.

Blood Coagulation↗

PubMed1999

Activation of CD4 T cells by somatic transgenesis induces generalized immunity of uncommitted T cells and immunologic memory.

Cellular immune responses were analyzed in vivo after a single intraspleen inoculation of DNA coding for a 12-residue Th cell determinant associated with a 12-residue B cell epitope, a process termed somatic transgene immunization. We show that CD4 T cells are readily activated and produce IL-2, IFN-gamma and IL-4, characteristics of an uncommitted phenotype. Linked recognition of the two epitopes coded in the same transgene promoted IgM-IgG1 switch and enhanced the total Ab response but had no effect on IgG2a Abs. Although originating in the spleen, T cell responsiveness was found to spread immediately and with similar characteristics to all lymph nodes in the body. A single inoculation was also effective in establishing long term immunologic memory as determined by limiting dilution analysis, with memory T cells displaying a cytokine profile different from that of primary effector T cells. These studies provide evidence that by initiating immunity directly in secondary lymphoid organs, an immune response is generated with characteristics that differ from those using vaccines of conventional DNA or protein in adjuvant administered in peripheral sites. Somatic transgene immunization can therefore be used to probe T cell responsiveness in vivo and represents a tool to further understanding of the nature of the adaptive immune response.

Animals↗

PubMed1999

Obstructive jaundice caused by tumor emboli from hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) presenting as obstructive jaundice due to intrabile duct tumor growth is being reported with increasing frequency. We describe our clinical experiences and evaluate the results of different operative procedures for this disease. A retrospective study was undertaken to review 18 patients with obstructive jaundice by tumor emboli from HCC during a 15-year period of time. We reviewed clinical features, types of operative procedures, operative findings, and survival in the patients. All patients on initial examination had recurrent episodic jaundice or cholangitis. Types of surgical procedures were choledochotomy with T-tube drainage alone in nine patients, choledochotomy with T-tube drainage followed by hepatectomy in six, and T-tube drainage followed by transcatheter hepatic arterial chemoembolization in the remaining three patients. Liver cirrhosis was the associated disease in 15 (83.3%). There were three postoperative deaths (16.7%). The mean survival time for nine patients with external drainage alone was 4.5 months. For the three patients with T-tube drainage and transcatheter hepatic arterial chemoembolization, mean survival time was 11 months. Six patients who had undergone hepatectomy had a better postoperative survival time, with 1 surviving for more than 3 years and another alive for 70 months, without evidence of recurrence at the moment. Jaundice is not necessarily a harbinger of advanced disease and a contraindication for surgery. Managed properly, these patients will have satisfactory palliation and occasional cure.

Adult↗

PubMed1999

[Intestinal bacterial translocation in patients with biliary tract diseases].

To determine whether intestinal bacterial translocation occurs in man, the authors cultured the tissues of mesenteric lymph nodes(MLNs), bile, portal and peripheral venous blood obtained prior to and during operation in 35 patients with biliary diseases. No positive peritoneal swab, portal blood and peripheral blood culture were shown. Thirteen of 20 patients with biliary obstruction (65%) had bacteria in their MLNs, while no positive MLN culture was found in 12 patients without biliary obstruction. The most common bacteria recovered from the MLNs were Gram-negative enteric bacilli. Thus, it is considered that extrahepatic biliary obstruction may induce intestinal bacterial translocation in man.

Adult↗

PubMed1998

Identification of thyroid hormone response elements in the human fatty acid synthase promoter.

To investigate the regulation of the human fatty acid synthase gene by the thyroid hormone triiodothyronine, various constructs of the human fatty acid synthase promoter and the luciferase reporter gene were transfected in combination with plasmids expressing the thyroid hormone and the retinoid X receptors in HepG2 cells. The reporter gene was activated 25-fold by the thyroid hormone in the presence of the thyroid hormone receptor. When both the thyroid hormone and the retinoid X receptors were expressed in HepG2 cells, there was about a 100-fold increase in reporter gene expression. 5'-Deletion analysis disclosed two thyroid hormone response elements, TRE1 (nucleotides -870 to -650) and TRE2 (nucleotides -272 to -40), in the human fatty acid synthase promoter. The presence of thyroid hormone response elements in these two regions of the promoter was confirmed by cloning various fragments of these two regions in the minimal thymidine kinase promoter-luciferase reporter gene plasmid construct and determining reporter gene expression. The results of this cloning procedure and those of electrophoretic mobility shift assays indicated that the sequence GGGTTAcgtcCGGTCA (nucleotides -716 to -731) represents TRE1 and that the sequence GGGTCC (nucleotides -117 to -112) represents TRE2. The sequence of TRE1 is very similar to the consensus sequence of the thyroid hormone response element, whereas the sequence of TRE2 contains only a half-site of the thyroid hormone response element consensus motif because it lacks the direct repeat. The sequences on either side of TRE2 seem to influence its response to the thyroid hormone and retinoid X receptors.

Base Sequence↗

PubMed1998

Experimental study on pathogenicity of precore mutants in Hepadnaviridae.

OBJECTIVE: To study the replicative competency and pathogenicity of precore gene mutants of duck hepatitis B virus (DHBV) in the duck model. METHODS: Three site-directed point mutations in the precore region of cloned DHBV were constructed. Head-to-tail dimers were formed. The three plasmids were named: pEDM1-2 (initiation codon ATG mutated to TTG), pEDM2-2 (an "A" was inserted down stream of codon 12, leading to frame shift in the distal end of precore region), pEDM3-2 (codon 38 was changed from TAT to TAA, leading to a stop codon at the 3'-end). Mutants and wild-type cloned DNA dimers were first separately used to transfect LMH cells (a chicken hepatoma cell line) and viruses were collected from supernatant and used to infect 6 one-day-old ducklings per group. Serum duck hepatitis B surface antigen (DHBsAg) and DHBV DNA were assayed. Six weeks after infection, ducks were killed and liver tissues were studied for histopathological changes. RESULTS: After transfection, pEDM1-2, pEDM2-2 and pEDM3-2 expressed similar level of DHBsAg. Replication of pEDM1-2 and pEDM3-2 was similar to that of the wild type clone, while pEDM2-2 replicated at a significantly decreased level. Infection study employing the supernatant of transfected cells was as follows: pEDM1-2 infected 5/6 ducklings, pEDM2-2 non infected, pEDM3-2 infected 2/6 ducklings, wild type virus infected 6/6 ducklings. Positive serum samples from both pEDM1-2 and pEDM3-2 were at a lower serum DHBV level compared to that of the wild type virus. Pathological changes were more significant in pEDM3-2 infected duck livers, with numerous inflammatory cells in portal tract and infiltration into parenchyma. CONCLUSIONS: Mutations in the initiating codon or generation of a stop codon at the 3'-end of the precore region resulted in decreased replication competency of DHBV, while frame-shift mutation of the precore region, covering the epsilon encapsidation signal abolished the replication of DHBV. When the mutants replicated in hosts, more severe pathological changes were observed in ducks infected with mutant harboring a stop codon at the 3'-end. Data suggest that replicative-competent DHBV precore mutant can be more pathogenic than wild-type DHBV.

Animals↗

PubMed1997

Effect of administration of malathion for 90 days on macrophage function and mast cell degranulation.

Previous studies have shown that acute, oral administration of malathion modulated the humoral immune response to T cell-dependent antigen, mitogenic responses, macrophage function and mast cell degranulation. In this report, the effects of malathion administration for 90 days on macrophage function, as measured by respiratory burst capacity, phagocytic capability and the production of cathepsin D, and mast cell integrity were assessed. A dose-dependent increase in respiratory burst activity was observed at all doses tested. The production of cathepsin D was elevated at doses of 1 mg/kg/day malathion or greater. The phagocytic capability of peritoneal macrophages was elevated at the dose of 0.1 mg/kg/day, but was suppressed at higher doses. The effect of oral administration of malathion for 90 days on the degranulation of mast cells, in both organs (skin and uterus) and peritoneal lavage fluid, was also assessed. Degranulation (both severe and slight) of mast cells from the skin and peritoneum was observed at a dose of 1.0 mg/kg/day or greater. In addition, the percentage of mast cells that were undegranulated was decreased. In the skin, but not the peritoneum, these effects were dose-dependent. In the uterus, the percentage of mast cells that were undegranulated was decreased and severely degranulated was increased at a dose of 0.1 mg/kg/day or greater. These data indicate that repeated administration of malathion increased macrophage function and led to mast cell degranulation at doses as low as 0.1 mg/kg/day for 90 days.

Administration, Oral↗

PubMed1997

In vivo role of B lymphocytes in somatic transgene immunization.

Immunity generated by in vivo inoculation of plasmid DNA is a straightforward and potentially valuable new approach to immunization. Little is known about the type of cells involved, the various immunological aspects, and the destiny of the transgene. In this report, we describe a system in which immunity is the result of in vivo targeting of B lymphocytes. This was accomplished using plasmid DNA encoding an immunoglobulin heavy-chain gene under the control of immunoglobulin promoter and enhancer elements. We show persistence of the transgene in splenic B lymphocytes for at least 3 months, i.e., the average life span of long-lived B lymphocytes in the mouse. The transgene could not be detected in any other lymphoid or nonlymphoid organs over a period of 6 months. We also established that the transgene is integrated in the host DNA. These studies bring new understanding to the events underlying the in vivo use of plasmid DNA. Moreover, the characteristics of this new approach make somatic transgene immunization a model system to study the immunogenicity of endogenous antigens in adult animals.

Animals↗

PubMed1997

Effects of malathion metabolites on degranulation of and mediator release by human and rat basophilic cells.

In the present study, the effects of malathion and malathion derivatives on histamine and beta-hexosaminidase release by RBL-1 cells, rat peritoneal mast cells (RPMC), and human peripheral blood basophils (HPBB) and cutaneous mast calls were examined. One hour of incubation of RBL-1 cells with all organophosphate compounds tested, except for malathion and malathion monoacid, led to an increase in histamine release. beta-Hexosaminidase, an enzyme released by basophilic cells and a biochemical marker of degranulation, was not released from RBL-1 cells after 1 h of exposure to organophosphate compounds. Within 4 h, all compounds tested increased the release of histamine and beta-hexosaminidase. Longer exposures led to a decrease in the concentration of the compound that was required to cause mediator release. Exposure of RPMC to organophosphate compounds, with the exception of malathion monoacid and malathion (30 min) or malathion monoacid (1 h), led to the release of histamine, but not beta-hexosaminidase. Incubation of HPBB with malaoxon (51.4 +/- 2.8% total histamine released), malathion diacid (25.7 +/- 2.9%), beta-malathion monoacid (31.4 +/- 2.8%), and isomalathion (57.1 +/- 17.1%) for 1 h led to the release of histamine. Only malaoxon and isomalathion caused beta-hexosaminidase release from HPBB after a 1-h incubation. Incubation of cutaneous mast cells with malaoxon and beta-monoacid for 4 h led to increased release of histamine and beta-hexosaminidase at levels comparable to compound 48/80. These data suggest that malathion metabolites can cause rapid release of histamine from basophilic cells from a variety of origins and species. With prolonged incubation, malathion itself caused the release of mast-cell mediators, suggesting that the cells may be capable of metabolizing malathion. These data also indicate a disparity between the release kinetics of two different mast-cell mediators contained in granules by organophosphates, and that there are different mechanisms of mediator release.

Animals↗

PubMed1997

Effect of administration of malathion for 14 days on macrophage function and mast cell degranulation.

Previous studies have shown that acute, oral administration of malathion modulated the humoral immune response to T-cell-dependent antigen, mitogenic responses, macrophage function, and mast cell degranulation. While administration of malathion for 14 days did not affect the generation of an immune response to antigen, it was possible that macrophage and mast cell functions were affected. In this report, the effect of malathion administration for 14 days upon these parameters were assessed. This treatment regimen increased the respiratory burst capacity to a maximal level at a dose of 1 mg/kg/day or greater. The effect of oral administration of malathion for 14 days on the degranulation of mast cells in various organs (heart, skin, and small intestine) and peritoneal lavage fluid was also assessed. At doses of 1 mg/kg/day and above, the number of mast cells that was undegranulated decreased and the number that was severely degranulated increased. There was no change in mast cell integrity in biopsies from heart and skin, and in peritoneal fluid after 14-day administration of 0.1 mg/kg/day. However, the number of mast cells associated with the small intestine that had undergone degranulation was increased at this dose of malathion. These data indicate that repeated administration of malathion increased macrophage function at doses as low as 1 mg/kg/day and led to mast cell degranulation at doses as low as 0.1 mg/kg/day.

Animals↗

PubMed1997

Contributions of inflammatory mast cell mediators to alterations in macrophage function after malathion administration.

Recent studies using mast cell-defined mice showed that the presence of mast cells was necessary for the increase in macrophage function observed after oral administration of malathion and reconstitution with bone marrow-derived mast cells restored the ability of malathion to increase macrophage function. In addition, the release of mast cell mediators (blocked by cromolyn) and histamine (action blocked by pyrilamine) was shown to be involved in the action of malathion on macrophage function. In the present study, the contribution of inflammatory mediators (i.e. arachidonic acid metabolites and tumor necrosis factor [TNF]) which may be generated by mast cells after oral administration of malathion, was examined. Controls in this study included the effects of the agent to be examined on: (1) resident peritoneal macrophages; and (2) macrophages elicited with pristane, and agent shown previously to stimulate macrophage function in the absence of mast cells. Intraperitoneal administration of indomethacin, and inhibitor of cycloxygenase, or neutralizing antibody to TNF 30 h before and 4 h after oral malathion blocked the ability of malathion to increase macrophage function, as measured by the generation of respiratory burst activity and the production of cathepsin D. On the other hand, administration of these agents to mice injected intraperitoneally with pristane did not affect the observed increase in cathepsin D production. Respiratory burst function after elicitation with pristane was slightly decreased (indomethacin) or not affected (antibody to TNF). The effect of intraperitoneal administration of nordihydroguaiaretic acid (NDGA), and inhibitor of both cycloxygenase and lipoxygenase, was also examined. Intraperitoneal administration of NDGA partially blocked the effects of oral administration of malathion on peritoneal macrophage function, but did not affect the function of resident pristane-elicited peritoneal macrophages. These data suggest that inflammatory mediators (potentially released from mast cells upon stimulation) contribute to the elevation in macrophage function observed after oral malathion administration.

Animals↗

PubMed1997

Effect of acute administration of malathion by oral and dermal routes on serum histamine levels.

Previous studies have shown that acute, oral administration of malathion increased the generation of a humoral immune response, stimulated macrophage function and caused mast cell degranulation and histamine release. In this study, the effect of acute administration of various doses of malathion via oral and dermal routes to mice and rats on serum levels of histamine was evaluated. Oral administration of malathion to mice led to an increase in the level of serum histamine 4 and 8 h after administration. At 4 h after administration, the peak in serum histamine levels was observed at a dose of 10 mg/kg malathion. At 8 h, a maximal effect was observed at a dose of 700 mg/kg and the response was more prolonged than at lower doses. At 12 and 24 h after administration, the level of histamine in the serum of treated mice was comparable to controls. A similar pattern was observed in rats. However, the time point at which histamine levels returned to control was 8 rather than 12 h. After application of malathion to the skin of mice or rats in dimethyl sulphoxide (DMSO), the level of histamine in the blood was also increased. As before, the peak increase was observed at 4 h after administration and the level had returned to control levels within 8 h (slight increase at 8 h in rats) after application. However, after dermal application the maximal levels of histamine in the serum were noted at the highest doses of malathion. The no effect levels for histamine in the blood after malathion administration to these two species by these two routes are as follows: (1) Mice, oral in corn oil, 0.1 mg/kg; (2) Rats, oral in corn oil, 0.1 mg/kg; (3) Mice, dermal in DMSO, 2 mg/kg; (4) Rats, dermal in DMSO--not determined (2 mg/kg low effect level).

Administration, Cutaneous↗

PubMed1997

Engineering vaccines with heterologous B and T cell epitopes using immunoglobulin genes.

Antibodies engineered in their variable domain to express epitopes of heterologous antigens-antigenized antibodies-function as immunogens. Only the third complementarity-determining region (CDR3) of the H chain has been used as the site of epitope expression, as this loop has the highest natural variability in length and amino acid composition. We demonstrate that the CDR2 can be engineered to express a 12-amino acid peptide, which is a T-cell determinant that enhances the response to a B-cell epitope peptide of Plasmodium falciparum expressed in the CDR3 of the same variable domain. Mice with this gene inoculated into the spleen mounted an antibody response against the B-cell epitope higher than mice receiving the gene coding for the B-cell epitope only. In vitro studies established that the two epitopes were independently immunogenic in vivo.

Animals↗

PubMed1997

Somatic transgene immunization with DNA encoding an immunoglobulin heavy chain.

A plasmid DNA containing a chimeric immunoglobulin heavy-chain gene with tissue-specific promoter and enhancer elements was used as a model system to study the events triggered by a single intraspleen DNA inoculation in adult C57Bl/6 mice. A single intraspleen inoculation was followed in a week by secretion of transgene immunoglobulins and production of immunoglobulin M (IgM) anti-immunoglobulins. Their kinetics of serum appearance were almost superimposable. While anti-immunoglobulin antibodies remained detectable for over 6 months, transgene immunoglobulins disappeared after 3-4 weeks. However, transgene mRNA was detected in the spleen for 4 months. A multiplex polymerase chain reaction (PCR) analysis on splenic genomic DNA 17 days after inoculation demonstrated that the transgene was integrated in the host chromosomal DNA. The nucleotide sequence of the rearranged VDJ region from splenic genomic DNA was identical to that of the parental plasmid DNA, hence ruling out that hypermutation had occurred. A booster injection of immunoglobulin encoded by the transgene on day 200 elicited a typical secondary immune response with IgG1 and IgG2b antibodies. These results demonstrate that a single inoculation of an immunoglobulin heavy-chain DNA targeted to spleen lymphocytes leads to spontaneous integration of the transgene into the host DNA, and that this is sufficient to initiate immunity and establish immunologic memory. Our data also show that minute amounts (<100 ng/ml) of an endogenously produced protein secreted in the microenvironment of a lymphoid tissue generate immunity and establish immunologic memory rather than tolerance.

Animals↗

PubMed1997

[Quantitative histological study of adult condylar proliferation zone].

The thicknesses and cell numbers of 43 adult condylar proliferation zone were observed by serial section and multiarea measurement in order to investigate the relationships between them and age. The samples were divided into three groups by age (19-45, 46-59, 60-74). By way of statistical analysis, the cell numbers and thicknesses of different areas of the same age group, different age of the same area, and the relationship between thicknesses and age was analysed. The results show that the average proliferation zone thickness is different among different age groups, it becomes thinner with the increase of age, and the cell number is decreased. There is high significant difference among different age groups (P < 0.01). But there is no significant difference of the proliferation zone thickness between the group of 45-59 years old and the older group (60-74)(P > 0.05). There is diverse correlation between thicknesses and age increase.

Adult↗

PubMed1997

[Quantitative detection of serum hepatitis B wild type virus and the precore mutant genomes using competitive polymerase chain reaction in patients with HBeAg(-) chronic hepatitis B].

We set up a competitive PCR assay to obtain simultaneously a quantitative estimation of HBV wild type (M0) and precore mutant (M1 M2) genomes in sera of patients with HBeAg negative chronic hepatitis B and their evolution during antiviral therapy. The results showed that the amount of HBV DNA declined to undetectable levels very rapidly after the beginning of therapy in responders, while in non responders, the amount of viral genomes decreased but without becoming negative. Wild type viral strains (M0) seemed to be more sensitive to interferon as compared to precore mutant strains (M2). This method may be useful to study the course of viral infection and to evaluate the efficacy of antiviral therapy.

Adult↗

PubMed1997

[Preliminary study on the arsenic trioxide-induced NB4 cell apoptosis and its molecular mechanisms].

OBJECTIVE: To illustrate the possible cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL). METHODS: APL cell line NB4 was used for in vitro studies. The effect of As2O3 on APL was studied by using flow cytometry, DNA electrophoresis, Narthern blotting and Western blotting. RESULTS: As2O3 induced NB4 cell apoptosis, while not inhibiting the growth and survival of two other leukemic cell lines (HL-60 and U937). Furthermore, As2O3 effectively down-regulated the expression of bcl-2 gene without changing the mRNA levels of other apoptosis-associated genes (including p53, c-myc, bax and bcl-XL). CONCLUSION: These might be one of the molecular mechanisms of As2O3 induced NB4 cell apoptosis.

Animals↗

PubMed1997

[Effects of arsenic trioxide on the subcellular localization of PML/PML-RARalpha protein in leukemic cells].

OBJECTIVE: In order to illustrate the possible roles of PML-RARalpha protein in arsenic trioxide (AsO3)-induced NB4 cell apoptosis. METHODS: Effects of As2O3 on the subcellular localization of PML-RARalpha in NB4 cells were studied. RESULTS: (1) Anti-PML serum staining was reduced and PML granules emerged in the perinuclear cytoplasm in a diffuse pattern in HL-60 cells under As2O3 treatment; (2) abnormal PML/PML-RARalpha granules were decreased; (3) NB4 cells accumulated anti-PML serum staining granules in the cytoplasms were increased and similar accumulation also found in apoptotic cells; and (4) pretreatment with all-trans retinoic acid (ATRA) for 24 or 48 hours did not alter the As2O3 effects. CONCLUSION: As2O3-induced apoptosis was independent of the retinoic acid signal pathway, and it might be regulated by PML/PML-RARalpha and/or other related genes.

Antineoplastic Agents↗