Biomedical subjects
Publications and source records attributed to J Geng.
For a better myocardium protection, we invented an irrigator. It can be used in any kinds of CPB machines, It can perfusate both crystal fluid and blood at the same time or separately. It can monitor the perfussion temperature and pressure And it can adjust the composition of perfussion fluid at will.
Leishmania are parasites that survive within macrophages by mechanism(s) not entirely known. Depression of cellular immunity and diminished production of interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha are potential ways by which the parasite survives within macrophages. We examined the mechanism(s) by which lipophosphoglycan (LPG), a major glycolipid of Leishmania, perturbs cytokine gene expression. LPG treatment of THP-1 monocytes suppressed endotoxin induction of IL-1 beta steady-state mRNA by greater than 90%, while having no effect on the expression of a control gene. The addition of LPG 2 h before or 2 h after endotoxin challenge significantly suppressed steady-state IL-1 beta mRNA by 90% and 70%, respectively. LPG also inhibited tumor necrosis factor alpha and Staphylococcus induction of IL-1 beta gene expression. The inhibitory effect of LPG is agonist-specific because LPG did not suppress the induction of IL-1 beta mRNA by phorbol 12-myristate 13-acetate. A unique DNA sequence located within the -310 to -57 nucleotide region of the IL-1 beta promoter was found to mediate LPG's inhibitory activity. The requirement for the -310 to -57 promoter gene sequence for LPG's effect is demonstrated by the abrogation of LPG's inhibitory activity by truncation or deletion of the -310 to -57 promoter gene sequence. Furthermore, the minimal IL-1 beta promoter (positions -310 to +15) mediated LPG's inhibitory activity with dose and kinetic profiles that were similar to LPG's suppression of steady-state IL-1 beta mRNA. These findings delineated a promoter gene sequence that responds to LPG to act as a "gene silencer", a function, to our knowledge, not previously described. LPG's inhibitory activity for several mediators of inflammation and the persistence of significant inhibitory activity 2 h after endotoxin challenge suggest that LPG has therapeutic potential and may be exploited for therapy of sepsis, acute respiratory distress syndrome, and autoimmune diseases.
We have shown that Leishmania lipophosphoglycan (LPG) inhibits IL-1 beta gene expression in human monocytes. Here, we show that LPG can bind in a time-dependent manner and suppress endothelial cell activation, possibly via specific LPG domains. Endotoxin (10 ng/ml, 4 h) consistently caused endothelium to increase monocyte adhesion (approximately 20-fold). LPG pretreatment (2 microM, 2 h) completely blocked endotoxin-mediated monocyte adhesion. LPG did not grossly suppress endothelial functions because TNF-alpha- and IL-1 beta-mediated adhesion toward monocytes were not affected. Using four highly purified LPG fragments (namely, repeating phosphodisaccharide (PGM), phosphoglycan, phosphosaccharide core-lyso-alkyl-phosphatidylinositol (core-PI), and lyso-alkyl-phosphatidylinositol (lyso-PI)), we examined whether these fragments can independently inhibit endothelial adhesion. In contrast to that of intact LPG, neither the four LPG fragments (2 microM, 2 h) independently nor the co-addition of phosphoglycan and core-P1 fragments blocked the endotoxin-mediated adhesion to monocytes. To determine whether the fragments can reverse the effect of intact LPG, endothelial cells were first pretreated with the LPG fragments (10 microM, 15 min), followed by the addition of LPG (2 microM). All four LPG fragments fully reversed the effect of LPG. Simultaneous addition of LPG fragments and intact LPG caused only partial suppression (approximately 45%), while the addition of LPG fragments 14 min later had no reversal effect. Flow cytometry revealed that only core-P1 and lyso-P1 competitively inhibited (approximately 30%) LPG binding. Conversely, LPG competed with the binding of [3H]lyso-P1 (approximately 30%). Furthermore, mAb against the PGM reversed (approximately 70%) the effect of LPG. Thus, the lyso-P1 domain on LPG mediates binding to endothelial cells, whereas the PGM domain mediates the cell inhibitory effect.
The high-output pathway of nitric oxide production helps protect mice from infection by several pathogens, including Mycobacterium tuberculosis. However, based on studies of cells cultured from blood, it is controversial whether human mononuclear phagocytes can express the corresponding inducible nitric oxide synthase (iNOS;NOS2). The present study examined alveolar macrophages fixed directly after bronchopulmonary lavage. An average of 65% of the macrophages from 11 of 11 patients with untreated, culture-positive pulmonary tuberculosis reacted with an antibody documented herein to be monospecific for human NOS2. In contrast, a mean of 10% of bronchoalveolar lavage cells were positive from each of five clinically normal subjects. Tuberculosis patients' macrophages displayed diaphorase activity in the same proportion that they stained for NOS2, under assay conditions wherein the diaphorase reaction was strictly dependent on NOS2 expression. Bronchoalveolar lavage specimens also contained NOS2 mRNA. Thus, macrophages in the lungs of people with clinically active Mycobacterium tuberculosis infection often express catalytically competent NOS2.
OBJECTIVE: To observe the effects of insulin and captopril on growth of mesangial cells and on production of interleukin-6 (IL-6) and tumor necrosis factor (TNF) in culture media of glomerular cells. METHOD: Streptozocin induced diabetic rats (DM rats) were compared with normal wistar rats. RESULTS: The CPM value of 3H-TdR incorporated into mesangial cells in DM rats was significantly higher than that in Wistar rats. When the culture media was added by 5 x 10(-4) U/ml, 5 x 10(-3) U/ml and 5 x 10(-1) U/ml of insulin, the CPM value incorporated into mesangial cells and the concentration of IL-6 in the culture media of both DM and wistar rats were significantly higher than those of the control (no insulin). When captopril (10(-6) mol/L, 10(-4) mol/L, 10(-3) mol/L) was added into the media in different concentration, the cpm value of 3H-TdR and the concentration of TNF in DM rats were significantly lower than those of the control (no captopril). But the CPM value of 3H-TdR in Wistar rats was lower than that in the control, which was only seen in the concentration of 10(-3)M captopril. CONCLUSION: Ins could promote 3H-TdR in corporation and increase the production of IL-6, and captopril inhibited 3H-TdR in corporation and decrease the production of TNF.
General character and rules of changes in psychic stress, and effects of psychic care with procedural and sensory information on these changes were observed in 600 patients with surgery, including general surgery, urinary surgery and gynecologic surgery. 300 cases were in experimental group, others were in two control groups, each group, with 150 cases. The results showed that: 1. after admission, as the approach of the date of operation the stress reaction increased graduatedlly, anxiety, fear and blood pressure reached the top in the night before operation, all of these changes went down as the performance of operation. Pain, suffering and malaise were severe after operation than that during operation. 2.Psychic index of stres reaction were lower in experimental group than that in two control groups, during the night before operation, in the operation and after operation. (P < 0.05, P < 0.01, P < 0.001), These results showed that psychic care are useful method to maintain health and comfort patients with surgical experience and have some practical value.
Infection with a sexually transmitted disease (STD) increases the risk for human immunodeficiency virus (HIV) infection. Polymorphonuclear leukocytes (PMNs) are recruited into the genital tract by STD pathogens, such as Chlamydia trachomatis. Semen of HIV-infected men contains HIV associated with mononuclear cells. This study investigated the interaction among PMNs from HIV-uninfected persons, C. trachomatis, and HIV-infected cells and examined the mechanisms for enhanced HIV replication. We demonstrated that PMNs from HIV-seronegative donors induced HIV replication in mononuclear cells from 17 HIV-infected patients in medium without exogenous IL-2. HIV in the cell-free supernatants from cocultures of PMNs and patients' peripheral blood mononuclear cells (PBMCs) was replication competent, as indicated by their capacity to propagate HIV in a second round of culture using PBMCs from HIV-seronegative individuals and by the fact that proviral DNA was found in these cells. PMNs from HIV-seronegative donors increased HIV replication over 100-fold in chronically HIV-infected cell lines of the monocytic, T, and B cell lineages. Moreover, PMNs increased U1 cells' production of p24 antigen by as much as ninefold when compared with U1 cells cocultured with PBMCs. The addition of C. trachomatis to PMN and U1 coculture increased HIV replication by an additional ninefold at 24 h, whereas C. trachomatis alone had no effect on p24 antigen production by U1 cells. Thus, C. trachomatis serves not only to recruit PMNs, but also to interact with PMNs to increase HIV replication. HIV replication is triggered by contact of HIV-infected cells with PMNs, by the generation of reactive oxygen intermediates (ROIs), and by soluble factors such as TNF-alpha and IL-6. This is based on the findings that production of p24 antigen, IL-6, and TNF-alpha induced by PMNs is abrogated by disrupting or partitioning PMNs from HIV-infected cells; is inhibited by superoxide dismutase and catalase, enzymes that destroy ROIs; is enhanced by differentiated HL60 cells capable of producing ROIs; and is induced by PMNs tested negative for CMV. Furthermore, the production of ROIs is independent of HIV infection of mononuclear cells, since PMNs cocultured with HIV-uninfected parental monocytic and T cell lines generated ROIs. Therefore, the increased risk for acquiring HIV infection associated with chlamydia cervicitis may be related to the local recruitment of PMNs by C. trachomatis and the induction of infectious virus from mononuclear cells present in semen. These observations provide a rationale for strategies to reduce HIV transmission by control of STD.
Multiple forms of cytochrome P450 (P450) in brain tissue have been demonstrated to be expressible in brain tissue using polymerase chain reaction (PCR) techniques, Northern blotting, hydroxylation activity assessment and cloning approaches. The antidepressant drug imipramine is metabolized by brain microsomes to multiple products by pathways inhibitable by quinidine, 7,8-benzoflavone, and ketoconazole, well-known inhibitors of P450-catalyzed reactions. Moreover, PCR studies revealed that a number of P450s are expressible in brain tissue and in glioma C6 cells. Quantitative PCR studies further demonstrated the response of many of these forms to induction in agreement with hydroxylation activity results.
The mixed function oxidase system consists of NADPH-cytochrome P450 reductase (P450 reductase) and various isoforms of cytochrome P450 (P450), which can catalyze the oxidation of a broad range of endogenous and exogenous compounds. In this study, we examined the rat glioma C6 cell line for the presence of P450 reductase and three isozymes of cytochrome P450, 1A1, 2B1, and 2B2, by reverse transcription followed by PCR (RT-PCR). Rat glioma C6 cells were treated with hepatic P450 inducers phenobarbital (PB) or benzo(a)anthracene (BA). Cytochromes P450 1A1, P450 2B1, and P450 2B2, and P450 reductase, were detected in all the different treatment groups. Restriction digestion was used to confirm the PCR fragments and the expected digestion products were obtained. The induction of P450 1A1 and 2B was quantified using competitive PCR. Ten- and five-fold inductions of P450 1A and 2B mRNA after BA or PB treatments, respectively, were detected by competitive PCR. Microsomes prepared from rat glioma C6 cells showed cytochrome P450 spectra with absorption at 450 nm. Ethoxyresorufin O-deethylase activity (11.5 +/- 1.7 pmol/min/mg of microsomal protein) and pentoxyresorufin O-dealkylation activity (8.9 +/- 1.4 pmol/min/mg of microsomal protein) confirmed the induction of P450 1A and 2B at the protein level in response to BA or PB treatments, respectively. These experiments provide further evidence that the rat glioma C6 cell line contains an active mixed function oxidase system that can be induced by hepatic P450 inducers.
Reverse transcription (RT)/polymerase chain reaction (PCR) was used to detect the expression of six isoforms of cytochrome P450 which belong to five P450 subfamilies in rat glioma C6 cell line. P450 1A2, 2A1, 2C7, 2E1 were identified by RT-PCR in all samples, including untreated cells as well as cells treated with phenobarbital (PB) or benzo(a)anthracene (BA). P450 3A and 2C11 were not detected in our glioma samples although they were detected in liver tissues in our previous study. To confirm proper PCR products, various restriction enzymes were used to digest the PCR fragments and the expected digestion patterns were obtained. These results demonstrate for the first time that glioma C6 cells, representing a single cell type of rat central nervous system (CNS), contain a P450-dependent metabolism system which seems important for understanding drug metabolism, neurotransmission as well as tumor etiology and chemotherapy in brain.
Molecular studies of chromosomal translocation (15;17) in acute promyelocytic leukemia (APL) have shown that retinoic acid receptor A (RARA) gene on chromosome 17 is juxtaposed to the PML gene on chromosome 15. This results in a PML-RARA chimeric gene. Our work has demonstrated that the PML breakpoints in APL patients are clustered in two limited regions, PML-bcr1 and PML-bcr2, separated from each other by about 10 kb. DNA sequence of PML-bcr1 and primary structure of the junctional region of reciprocal chromosomal translocation in a patient have been determined in this paper. Compared to those of two previously reported cases abroad, we found that the breakpoint may be situated in the topoisomerase II cleavage site. A working model has been proposed for the mechanism of DNA illegitimate recombination in t (15;17).
The study reports treatment and follow-up of compulsive drug-consuming patients (mainly of coca paste). The program used was based on a behavioral cognitive and instructional model. The traditional functional analysis was modified to include the therapeutical work in seven behavioral areas: (1) drug use; (2) behavior during free time; (3) behavior at work; (4) social behavior; (5) self- and environmental management behaviors; (6) problem solving and decision-making behaviors; (7) recognition, evaluation, and modification of irrational beliefs. For each area objectives, therapeutical procedures, control and evaluation methods, and termination criteria were determined. Patients engaged in a multiple activity program and received individual and group therapy. Out of 223 male patients, 130 were discharged (that is, they fulfilled all the conditions stated by the program) and 93 patients abandoned treatment. For evaluation purposes a test was used to determine the accomplishment of the behavioral objectives. Follow-up interviews after 6 to 72 months showed that although 24 patients relapsed to drug use, 106 (81.48%) of the patients who had finished the program restrained from using drugs and obtained high scores in all seven behavioral areas.
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