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Biomedical subjects

J Q Chen

Publications and source records attributed to J Q Chen.

At least 19 recordsLinked to original sources

Distinct leukemia phenotypes in transgenic mice and different corepressor interactions generated by promyelocytic leukemia variant fusion genes PLZF-RARalpha and NPM-RARalpha.

Acute promyelocytic leukemia (APL) is characterized by a specific chromosome translocation involving RARalpha and one of four fusion partners: PML, PLZF, NPM, and NuMA genes. To study the leukemogenic potential of the fusion genes in vivo, we generated transgenic mice with PLZF-RARalpha and NPM-RARalpha. PLZF-RARalpha transgenic animals developed chronic myeloid leukemia-like phenotypes at an early stage of life (within 3 months in five of six mice), whereas three NPM-RARalpha transgenic mice showed a spectrum of phenotypes from typical APL to chronic myeloid leukemia relatively late in life (from 12 to 15 months). In contrast to bone marrow cells from PLZF-RARalpha transgenic mice, those from NPM-RARalpha transgenic mice could be induced to differentiate by all-trans-retinoic acid (ATRA). We also studied RARE binding properties and interactions between nuclear corepressor SMRT and various fusion proteins in response to ATRA. Dissociation of SMRT from different receptors was observed at ATRA concentrations of 0.01 microM, 0.1 microM, and 1.0 microM for RARalpha-RXRalpha, NPM-RARalpha, and PML-RARalpha, respectively, but not observed for PLZF-RARalpha even in the presence of 10 microM ATRA. We also determined the expression of the tissue factor gene in transgenic mice, which was detected only in bone marrow cells of mice expressing the fusion genes. These data clearly establish the leukemogenic role of PLZF-RARalpha and NPM-RARalpha and the importance of fusion receptor/corepressor interactions in the pathogenesis as well as in determining different clinical phenotypes of APL.

Animals

Extracorporeal immunoadsorption compared to avidin chase: enhancement of tumor-to-normal tissue ratio for biotinylated rhenium-188-chimeric BR96.

UNLABELLED: Based on the biodistribution and kinetics of biotinylated 188Re-chimeric BR96 (chiBR96), the enhancement of the tumor-to-normal tissue (T/N) radioactivity ratio using extracorporeal immunoadsorption (ECIA) was evaluated and compared with that of avidin "chase" in colon carcinoma-isografted Brown Norwegian rats. METHODS: Extracorporeal immunoadsorption (ECIA) was performed 6 or 12 hr after intravenous administration of biotinylated 188Re-chiBR96. Radioactivity redistribution was investigated just after ECIA [8 or 14 hr postinjection of the antibody] and 40 or 34 hr after ECIA performance (48 hr postinjection). Avidin was administered intraperitoneally at 6 hr postinjection. Tumor radioactivity uptake and T/N activity ratios of biotinylated 188Re-chiBR96 were compared using ECIA and avidin chase and were also compared with controls. RESULTS: Both ECIA and avidin chase can rapidly increase the radioactivity tumor-to-blood ratio without significantly interfering with the tumor uptake. ECIA at 8 hr postinjection increased the T/N ratios in blood-rich tissues, such as liver and bone marrow, from 6 and 8 to 10 and 18, respectively. Corresponding T/N ratios at 14 hr increased from 9 and 10 to 24 and 36. In contrast, when avidin chase was used, there were no T/N improvements, except in blood. Moreover, avidin chase caused a significant accumulation of radioactivity in the liver. CONCLUSION: The ECIA approach, with direct removal of unbound circulating biotinylated 188Re-chiBR96, thus can rapidly improve and maintain T/N ratios without overloading the liver with radioactivity, in contrast to avidin chase.

Animals

Production of human insulin in an E. coli system with Met-Lys-human proinsulin as the expressed precursor.

The construction of a gene encoding Lys-human proinsulin, its direct expression in E. coli, and the simple purification procedure are described here. The temperature inducible promotor was employed for induction in a very short time. The expression level could reach 20-30%. After simple downstream processing and only one step of Sephadex G50 purification, 150 mg recombinant Lys-human proinsulin with a purity of up to 90% could be obtained easily from 1 L of high density fermentation medium. The obtained product is in the form of Met-Lys-human proinsulin because of the failure of the bacterial host to remove the initiator methionine residue. The Lys-human proinsulin could be changed into human insulin by trypsin and carboxypeptidase B treatment in later steps. After separation with DEAE-Sephadex A25, human insulin with expected amino acid composition and full native biological activity could be obtained with a yield of 50 mg/L of fermentation medium.

Base Sequence

Suppression of the constitutive expression of cytochrome P-450 2C11 by cytokines and interferons in primary cultures of rat hepatocytes: comparison with induction of acute-phase genes and demonstration that CYP2C11 promoter sequences are involved in the suppressive response to interleukins 1 and 6.

Hepatic expression of various members of the cytochrome P-450 (CYP) superfamily is suppressed during inflammatory responses. We have shown that the specific expression of P-450 2C11 in male rat liver is suppressed transcriptionally by endotoxin treatment. To investigate the molecular mechanisms underlying this phenomenon, we studied the effects of the inflammatory cytokines interleukin (IL)-1, IL-6, tumor necrosis factor-alpha (TNF), interferon (IFN)-alpha, and IFN-gamma on the expression of P-450 2C11 and the mRNAs of two typical acute-phase protein genes, alpha 1-acid glycoprotein (AGP) and fibrinogen, in primary hepatocyte cultures. IL-1, IL-6, TNF, and IFN-alpha all suppressed P-450 2C11 mRNA, whereas IFN-gamma had no effect. IL-1 and TNF were more effective than IL-6 in the suppression of P-450 2C11 mRNA. Whereas IL-1 and IL-6 effects on P-450 2C11 were accompanied by induction of AGP and fibrinogen mRNAs, IFN-alpha and TNF treatments had no effects on AGP. The suppression of P-450 2C11 and the induction of AGP by IL-1 showed similar time courses. The combination of IL-1 and IL-6 showed additivity in suppression of P-450 2C11, at maximally effective concentrations of cytokines. The effects of IL-1 on P-450 2C11 and AGP expression were blocked by IL-1 receptor antagonist protein. We also studied the effects of IL-1 and IL-6 on the transient expression of chloramphenicol acetyl-transferase reporter gene constructs containing 200 or 1287 base pairs of the 5' flanking region of the CYP2C11 gene, transfected into primary hepatocytes. The chloramphenicol acetyltransferase activities in cells transfected with the 200-base pair construct were reduced to about 33% and 58% of control levels by treatment with IL-1 or IL-6, respectively, suggesting that sequences important for cytokine down-regulation lie within the proximal promoter region of the CYP2C11 gene.

Acute-Phase Reaction

[Rational evaluation of different lymph node dissection].

To evaluate the effect and indication of different lymph node dissection (D1+, D2, D3), we performed radical operations for 371 cases of gastric cancer. The results showed that D1+ or D1 lymph node dissection was enough for gastric cancer of Ia stage, D2 was suitable for Ib stage. For localized or massive type gastric cancer of II + III stage, D3, D2 dissection was better than D1+ dissection. For the gastric cancer of the same type in IV stage, the 5-year survival rate after D3 + D2 dissection was 42.9%, but for the gastric cancer of infiltrative type or diffused growth pattern in II + III stage, the effect was not significantly increased even after the D3, D2 dissection. For the gastric cancer of this type in IV stage, the effect was not improved after the extended lymph node dissection. Extended dissection needn't be performed if there was no lymph node metastasis. D3, D2 dissection was better if there was little lymph node metastasis or the metastasis was limited to 1st group. For those metastasized to 2nd group or the quantity was more, D3 was better than D2, D1+. The effect of D3, D2 dissection was not significantly improved in the extensive metastasis case (more than 10 or to the 3rd group).

Adult

Historical total and respirable silica dust exposure levels in mines and pottery factories in China.

Historical exposure estimates of total dust and respirable silica were made in a recent nested case-referent study of lung cancer among mine and pottery workers in China. Exposure to total dust and respirable silica was assessed in 20 mines and 9 pottery factories. The average total dust concentration was 7.26 mg center dot m-3, with a range from 17.68 mg center dot m-3 in the 1950s to 3.85 mg center dot m-3 in the 1980s, while the average respirable silica dust was 1.22 mg center dot m-3, with a range from 3.89 mg center dot m-3 in the 1950s to 0.43 mg center dot m-3 in the 1980s. The highest respirable silica dust occurred in the underground mining operations (1.43 mg center dot m-3), particularly for manual drillers (9.03 mg center dot m-3). Among all facility types, tungsten mines had the highest respirable silica dust exposure (1.75 mg center dot m-3), while the lowest exposure occurred in copper-iron mines (0.32 mg center dot m-3).

Ceramics

Indirect validation of a retrospective method of exposure assessment used in a nested case-control study of lung cancer and silica exposure.

Validations of retrospective methods of assessment used in occupational epidemiological studies have rarely been published. This study is an indirect validation of a quantitative retrospective assessment of exposure to silica used in a nested case-control study of lung cancer among workers at 29 metal mines and pottery factories in China. Indices of cumulative total dust and cumulative respirable dust were calculated by merging work histories with the historical exposure profile for each subject. To validate indirectly the methods of exposure assessment used in the study of lung cancer, trends for exposure response relation between the two indices of exposure to silica and risk of silicosis were evaluated with 376 patients with silicosis from the study population as the cases, and 1262 controls without silicosis for comparison. Age adjusted odds ratios (ORs) as a measure of risk of silicosis showed striking trends with both indices of exposure to silica. For cumulative respirable dust, the OR (95% confidence interval) rose from 7.6 (5.1-11.4) for low exposure to 20.0 (13.2-30.6) for medium exposure, and to 51.7 (31.0-86.8) for high exposure. The strength of the association between exposure to silica and risk of silicosis suggests that the retrospective assessment of exposure used in the case-control study of lung cancer would accurately reflect an exposure response relation between silica and lung cancer, if it existed.

Case-Control Studies

Effects of Panax notoginseng saponins on myocardial adenosinetriphosphatase.

Effects of total Panax notoginseng saponins (PNS) and Panax notoginseng saponin monomers Rb1 and Rg1 (Rb1, Rg1) on total ATPase and Na(+)-K(+)-exchanging ATPase of guinea pig heart were studied. It was found that PNS inhibited the total myocardial ATPase, but had no significant effect on the myocardial Na(+)-K(+)-exchanging ATPase. The total ATPase was inhibited by Rg1, and more clearly by Rb1. The automaticity and contractility of isolated guinea pig atria were inhibited by Rb1. Rg1 decreased the spontaneous frequency of isolated guinea pig right atrium, but not markedly the contractility of the left atrium. These results demonstrate that Rb1 is the main ingredient in PNS.

Adenosine Triphosphatases

[Homoplastic keratomileusis for aphakic eyes with corneal leucoma].

We performed homoplastic keratomileusis on 6 aphakic eyes with central corneal leucoma. The results showed that the post-operative corrected visual acuities were markedly increased to 0.3-0.5 in 3 cases and to 0.1-0.2 in another 3 cases. Since such patients were neither indicated to undergo intraocular lens implantation or penetrating keratoplasty for various reasons nor indicated for epikeratoplasty, homoplastic keratomileusis can be chosen for them.

Adult

[Effects of different lymph node clearances on long-term survival in patients with gastric carcinoma].

From 1980 to 1987, radical gastrectomy plus R2 or R3 lymph node clearance was performed in 309 cases of gastric carcinoma of which 179 were with R2 and 130 with R3. The 1, 3, 5 years survival rate of R3 was statistically higher than that of R2. The 5 years survival rate of R2 was nearly the same as R3 in patients at stage I (I a, I b) and borrmann type I and II, While R3 yields better results than R2 at stage II and III a, it was even 25.5% higher by R3 than by R2 at II b and IV. R3 still benefits patients at stage II with serosa infiltration, R3 should also be performed in advanced cases with poorly biologic behavior, such as diffuse growth pattern; undifferentiated cancer and lymphatic cancerous embosis. The recovery time, complications and mortalities of patients with R2 or R3 were mainly related to the model of gastrectomy not to the extent of lymph node clearance.

Adult

[Corneal topography of keratoconus].

A computerized video keratoscope (TMS-1) was used to determine the topographic findings of 6 eyes of 4 patients with keratoconus and they were compared with those of 18 normal eyes. The results show that in keratoconus the central corneal refractive power is greater, the difference between the refractive powers of the bilateral central corneas of a case is larger and the inferior cornea is steeper than the superior cornea. The above topographic findings are possibly the characteristics of the corneal topography of keratoconus.

Adolescent

[An immunohistochemical study of cornea and adjacent bulbar conjunctiva in Mooren's ulcer].

The specimens of the corneal lesions and their adjacent bulbar conjunctivas taken from 14 cases with Mooren's ulcers were studied by immunohistochemical techniques to investigate the expression of HLA-DR antigen and the subgroups of lymphocytes. It is discovered that there is an aberrant expression of HLA-DR antigen in a large amount of keratoconjunctival epithelial cells and stromal keratocytes and simultaneously, the CD4/CD8 ratio is significantly higher than that of the normal control group. The results suggest that the aberrant expression of MHC-II antigen in the resident cells at the peripheral cornea and its adjacent conjunctiva and a raised local TH/TS ratio leading to an excessive autoimmune reactivity be possibly the direct cause of the pathogenesis of the Mooren's ulcer.

Adult

[Factors of graft failure after chemical corneal injury].

83 cases (97 eyes) of keratoplasty after chemical corneal injury were followed up for a mean 14 months with the results that 21 (21.6%) grafts were transparent and 76 (78.4%) opaque or semitransparent. The success rate depended on the severity of the chemical injury; it was 87.5% for type A corneal scarring and 15.7% for type B. The causes of graft failure were postoperative epithelial erosion (70.7%) and corneal rejection (28.0%). Most patients with epithelial erosion had problems of insufficient tear secretion and tear-film defects. The prevention and management of graft failure were discussed.

Adolescent

[Vitrectomy under temporary keratoprosthesis].

In vitreoretinal disorders complicated by corneal opacity, a temporary keratoprosthesis device is placed into a trephined opening in the cornea to provide a clear stable view which permits the performance of pars plana vitrectomy and immediately following the vitrectomy, the keratoprosthesis is replaced by a corneal graft. Using this technique, we have saved blind eyes with corneal and vitreoretinal disorders in one surgical procedure, being a new approach for rehabilitation of eye sight. Since 1990, the operation has been performed on 10 patients of whom 9 obtained satisfactory results. They were the patients who had been impossible to be saved by other methods and had been abandoned. The patient with the best result had been followed for 15 months and his visual acuity achieved and maintained 0.3. In six cases, the operation was combined with multiple procedures in the vitreous, such as gas fluid exchange, internal drainage of subretinal fluid, injection of silicone oil, etc. to facilitate the reattachment of the complicated retinal detachment.

Cornea

[Experimental pharmacokinetic studies of carboplatin intraperitoneal chemotherapy].

High performance liquid chromatography was used to study the performances of carboplatin by intraperitoneal (ip) administration in six dogs. 30 mg/kg carboplatin in 500ml 0.9% sodium chloride was injected ip quickly. Drug levels in the peritoneal fluid and blood of the portal vein and femoral vein were measured at different time intervals. The results showed a high drug concentration in the peritoneal fluid within 240 minutes after large dose and volume of carboplatin administered ip. The peak and mean concentrations of carboplatin in the peritoneal fluid were 139 and 64 times that of blood in the femoral vein, respectively. The peak and mean concentrations of the drug in the portal vein were 13.3 and 6.8 times those in the femoral vein. Intraperitoneal chemotherapy of carboplatin can maintain a stable and persistent high drug level in the peritoneal cavity, portal vein as well as liver. Systemic toxic effects were decreased due to low level of drug in the systemic circulation. These pharmacokinetic properties of carboplatin are of advantage in preventing and treating tumor recurrence in the peritoneal cavity and hepatic metastases.

Animals