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Biomedical subjects

Q Chen

Publications and source records attributed to Q Chen.

At least 613 records · Page 34Linked to original sources
PubMed1995

Distinct muscarinic receptors and signal transduction pathways in gallbladder muscle.

Acetylcholine (ACh) caused a dose-dependent contraction of gallbladder muscle cells in either a normal (1.9 mM) Ca2+, zero-Ca2+ or 4 mM Sr2+ medium, with a maximal contraction about 21 +/- 1% at 10(-6) M. Pirenzepine, methoctramine and p-fluoro-hexahydro-sila-difenidol (the M1, M2 and M3 antagonist, respectively) alone had no inhibitory effect on ACh-induced contraction in normal Ca2+ medium, which was blocked by the combination of methoctramine and p-F-HHSiD. In the 4 mM Sr2+ medium, methoctramine dose dependently inhibited ACh-induced contraction and shifted the ACh dose-response curve to the right. The contraction induced by ACh was further blocked by 10(-4) M propranolol (phosphatidic acid phosphohydrolase inhibitor that prevents the production of diacylglycerol from phospholipase D activation), 10(-5) M H-7 and chelerythrine (the protein kinase C inhibitors) by 64%, 75% and 77%, respectively. In contrast, in the zero-Ca2+ medium, p-fluoro-hexahydro-sila-difenidol dose-dependently inhibited ACh-induced contraction and shifted the ACh dose-response curve to the right. The action of ACh was further blocked by 10(-6) M U-73122 (phospholipase C inhibitor) and 10(-5) M CGS 9343B (calmodulin antagonist) by 95% and 77%, respectively. In conclusion, ACh contracts the gallbladder muscle by stimulating the M2 and M3 muscarinic receptors. The M2 receptors are linked to Ca2+ influx, activation of phospholipase D and protein kinase C-dependent pathway, whereas the M3 receptors are preferentially associated with the activation of phospholipase C, intracellular Ca2+ release and calmodulin-dependent pathway.

Acetylcholine↗
PubMed1995

[Prognostic factors in endometrial cancer: apropos of 206 cases treated at the Curie Institute].

From January 1, 1983 to December 31, 1990 two hundred and six patients with an invasive, non metastatic endometrial carcinoma were first treated at Institut Curie. Initial tumoral staging (TNM) was as follows: stage Ia: 48%, stage Ib: 31%, stage II: 15% and stage III-IV: 6%. Total hysterectomy or colpohysterectomy was performed in 186 cases, with a bilateral oophorectomy in 180 cases. Bilateral limited pelvic lymphadenectomy was performed in 116 cases. Brachytherapy was performed in the pre-operative setting in 25 cases, in the post-operative setting in 134 cases. Only five patients had brachytherapy alone, because of poor medical condition. External irradiation was exclusive in 15 cases and added to surgery for 68 patients. Median follow-up is 61 months (8-122 months). Five-year survival rate is 77% (71-83%); 5-year specific survival rate is 81% (75-87%). Independent prognostic factors for survival in multivariate analysis (Cox regression model) are tumoral stage (p < 0.0001), ovarian involvement (p < 0.0001), histologic node involvement (p = 0.005) and grade (p = 0.01). For local relapse, independent risk factors in the same analysis are ovarian involvement (p = 0.0004), tumoral stage (p = 0.01), age (p = 0.02) and histologic involvement of cervix (p = 0.04). For distant failure, independent risk factors are histologic node involvement (p = 0.0001), tumoral stage (p = 0.002) and grade (p = 0.003).

Adenocarcinoma↗
PubMed1995

[The relationship between 4-hydroxynonenal-derived epitopes on apolipoprotein B and coronary heart disease].

When lipid peroxidation takes place in plasma low density lipoprotein (LDL), a lot of aldehydes-derived epitopes are generated. To explore the relationship between these aldehydes-derived epitopes on apolipoprotein B (apo B) and coronary heart disease (CHD), we used both antibody against 4-hydroxynonenal (HNE)-derived epitopes and antibody against apo B to establish a sandwich enzyme-linked immunoassay (ELISA). The sera from 160 normal controls as well as from 103 patients with CHD were tested by ELISA for the expression of HNE-derived epitopes on apo B. The measurements showed that the mean expression of HNE-epitopes in the patients with CHD (183.5 +/- 63.6 mg/L, n = 103) was higher than that of normal controls (133.3 +/- 47.5 mg/L, n = 160). The difference of the expression of HNE-epitopes on serum apo B between the patients and normal controls was statistically significant. The results analysed by a multiple regression demonstrated that the expression of HNE-epitopes, levels of LDL-cholesterol and age were positively related to CHD, while the levels of HDL-cholesterol and female were negatively related to CHD. Thus, it was proven for the first time that the enhanced expression of HNE-epitopes on apo B might be an independent risk factor of CHD.

Aldehydes↗
PubMed1995

[Evaluation of surgical treatment for patients with multiple aldosteronoma: analysis of 11 cases].

From 1957 to 1994, 332 patients underwent surgical treatment for aldosteronoma at Ruijin Hospital. Among them, 11 patients (3.9%) were diagnosed as having multiple aldosteronoma. We ususally used the same method to make the qualitative diagnosis for both single and multiple aldosteronoma. In our experience, however, it was difficult to distinguish the unilateral multiple aldosteronoma by rutine B-type ultrasonography, CT or gamma-scintigraphy before surgery. The correct diagnosis could be obtained only by carefully exploring during the adrenal operation and a satisfactory prognosis also can be acquired if multiple aldosteronoma could be removed completely.

Adenoma↗
PubMed1995

Immunoglobulin depositions in peripheral nerves in polymyositis.

An immunocytochemical study was performed in 6 peripheral nerve specimens from 6 cases of polymyositis. The results revealed that depositions of IgG, IgM, IgA and C3 were found in the epineurium, perineurium and the walls of capillaries. These findings demonstrated that depositions of immunoglobulins and the complement-mediated immunoreaction may play an important role in pathogenesis of polymyositis with peripheral nerve involvements.

Adult↗
PubMed1995

[Influence of acupuncture on blood pressure, contents of NE, DA and 5-HT of SHR and the interrelation between blood pressure and whole blood viscosity].

Twenty spontaneous hypertensive rats (SHR) with systolic blood pressure (SBP) >or= 20 kPa were chosen and divided randomly into two groups (acupuncture group and control group). The former was acupunctured on bilateral Quchi (L1 11), Zusanli (ST 36). Another 46 immature SHRs which were about 7-week-old with SBP ranged from 16 kPa to 20 kPa were given 10% high molecular weight dextran (HMWD) or normal saline by intervention respectively. The results showed: 1. After three course of acupuncture, SHRs' SBP dropped remarkably from 25.493 +/- 0.73 kPa to 19.547 +/- 0.555 kPa (P < 0.01); 2. After three courses of acupuncture, NE and 5-HT contents in plasma were lowered (P < 0.05, < 0.01) and DA content in plasma was increased (P < 0.05) compared with that in the control group. 3. After three course of acupuncture, NE content in brainstem, hypothalamus, cerebral cortex increased (P < 0.005-0.01) and DA content in brainstem, cerebral cortex increased remarkably (P < 0.005-0.01) compared with that in the control group. 5-HT content in brainstem, hypothalamus, and cerebral cortex increased obviously compared with that in the control group. 4. After 1 or 2 hours of intervention of 10% HMWD to immature SHR, the whole blood viscosity and blood pressure rise remarkably compared with normal saline group. The experiment implies that the mechanism of lowering the blood pressure of SHR by acupuncture lies in that it can adjust NE, DA and 5-HT contents in plasma and central nervous system to adjust the activity of sympathetic, reduce whole blood viscosity etc.

Animals↗
PubMed1994

Integrin-mediated cell adhesion activates mitogen-activated protein kinases.

Integrins can function as signal-transducing receptors capable of modulating cell growth and gene expression (Juliano, R. L., and Haskill, S. (1993) J. Cell Biol. 120, 577-585; Hynes, R. O. (1992) Cell 69, 11-25). An early event in integrin signaling in fibroblasts and other cells involves activation of pp125FAK, a cytoplasmic tyrosine kinase (Hanks, S. K., Calalb, M. B., Harper, M. C., and Patel, S. K. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 8487-8491; Schaller, M. D., Borgman, C. A., Cobb, B. S., Vines, R. R., Reynolds, A. B., and Parsons, J. T. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 5192-5196). Here we report a novel aspect of integrin-mediated signal transduction. We demonstrate that adhesion of cells to substrata coated with extracellular matrix proteins, or with a synthetic peptide containing the RGD sequence, can cause activation of mitogen-activated protein (MAP) kinases in 3T3 or REF52 fibroblasts. Activation of MAP kinases seems to depend on integrin engagement rather than simply on cell attachment. Thus, MAP kinases are activated when cells adhere to substrata coated with the integrin ligands fibronectin or laminin, but not when cells adhere to poly-D-lysine, a nonspecific adhesion-promoting polypeptide. Treatment of cells with cytochalasin D, an inhibitor of actin microfilament assembly, almost completely blocks adhesion-induced MAP kinase activation, indicating a critical role for the cytoskeleton. In REF52 cells, we have observed that activation of MAP kinases is accompanied by redistribution of the protein to the nucleus, suggesting that the activated kinases may impinge on factors regulating gene expression. Thus, integrin-mediated cell adhesion seems a sufficient stimulus to cause activation and nuclear translocation of MAP kinases. This may have important implications for the regulation of cell growth and differentiation by the extracellular matrix.

3T3 Cells↗
PubMed1994

Postoperative bone re-growth in lumbar spinal stenosis. A multivariate analysis of 48 patients.

STUDY DESIGN: Forty-eight patients who underwent posterior decompressive surgery for lumbar spinal stenosis were studied. The effect of bone re-growth after posterior decompression in lumbar spinal stenosis on clinical outcome and the factors promoting the bone re-growth were investigated with a multivariate analysis model. METHODS: Bone re-growth at the sites operated upon was evaluated as a percentage of re-growth of the original laminectomy site based upon plain radiographs. The degree of bone re-growth was classified into four groups: 1) no significant re-growth (Group I, bone regrowth rate 10% or less); mild (Group II, 11% to 40%), moderate (Group III, 41% to 70%), and marked (Group IV, 71% to 100%). The average follow-up period was 4.5 years (range, 2 to 7 years). RESULTS: No significant bone re-growth was shown in 6% of the patients. Mild re-growth was shown in 50%, moderate re-growth in 29%, and marked re-growth in 15%. A multivariate analysis indicated that a total block in the preoperative myelogram, a follow-up period of more than 5 years, decompression at more than three spinal levels, and age under 60 years were associated with moderate or marked bone re-growth. Spinal instability accelerated the bone re-growth mainly in the mid and later follow-up intervals. Spinal levels adjacent to a fusion showed more bone re-growth. Patients with moderate and marked bone re-growth had poorer clinical outcomes than those with no significant and mild bone re-growth. CONCLUSION: Bone re-growth in a surgical defect will occur in most patients after posterior decompression. Moderate and marked postoperative bone re-growth are possibly related to recurrence of neurologic symptoms in the middle of and later on in follow-up periods.

Aged↗
PubMed1994

Time-resolved fluorescence studies of tomaymycin bonding to DNA.

Tomaymycin is an antibiotic that reacts at guanine N2 in the minor groove of the DNA helix. The number and type of tomaymycin-DNA adducts present on natural sequence DNA were identified using time-resolved fluorescence spectroscopy. At low bonding density, only two discrete species were observed with lifetimes of 4.3 and 7.1 ns and relative amplitudes of 40% and 60%. These two lifetime species are proposed to represent either R5' or S5' and S3' binding modes at the preferred bonding sequence 5'-AGA. R and S denote the configuration at C11 of tomaymycin, and 5' and 3' describe the orientation of the aromatic ring on the covalently modified strand. These two species were present over a range of solution conditions, including pH, nucleotide to drug ratio, DNA concentration, and DNA size. They have the same emission spectra, but slightly shifted absorption spectra. The weak temperature dependence of the fluorescence lifetimes presumably is due to the excited-state proton-transfer reaction that quenches tomaymycin fluorescence. The rate of formation of the longer lifetime species of DNA adduct is about twice as fast as that of the shorter lifetime species. Under saturating conditions, the fluorescence decay shows a bimodal lifetime distribution whether analyzed by least-squares assuming a Gaussian distribution model or by the maximum entropy method. The two groups of lifetimes are centered around 2-3 and 6-6.6 ns, reflecting multiple species on different bonding sequences.

Antibiotics, Antineoplastic↗
PubMed1994

Senescence-like growth arrest induced by hydrogen peroxide in human diploid fibroblast F65 cells.

Human diploid fibroblast cells lose replicative potential after a certain number of population doublings. We use this experimental system to investigate the role of oxidative damage in cellular aging. Treating cells with H2O2 at < 300 microM did not affect the viability of the majority of cells when judged by morphology, trypan blue exclusion, and protein synthesis. However, the treatment caused a dose-dependent inhibition of DNA synthesis. After a 2-hr treatment with 200 microM H2O2, the cells failed to respond to a stimulus of serum, platelet-derived growth factor, basic fibroblast growth factor, or epidermal growth factor by synthesizing DNA, and the loss of response could not be recovered by 4 days. Subcultivation showed that, as in senescent cells, division of the treated cells was inhibited. The life-time cumulative growth curve showed that the loss of replication due to H2O2 treatment was cumulative and irreversible. The H2O2 treatment decreased the number of the population doublings in the rest of the life span by 35.3 +/- 10.3%. Enzymatic assays indicated that, like the cells in their senescent state, the treated cells were less able to activate ornithine decarboxylase and thymidine kinase. Furthermore, subcultivation after the H2O2 treatment showed that the cells developed the morphology of senescent cells. In conclusion, sublethal treatment of H2O2 "stunned" F65 cells and caused the cells to enter a state resembling senescence.

Amino Acids↗
PubMed1994

A 21-kDa chloroplast heat shock protein assembles into high molecular weight complexes in vivo and in Organelle.

The conservation of the carboxyl-terminal "heat shock" domain among small (sm) cytoplasmic and chloroplast heat shock proteins (HSPs) suggests that these smHSPs perform similar functions. Previous studies have established that cytoplasmic smHSPs are found in higher order structures in vivo (approximately 500 kDa). To determine if the chloroplast smHSP is found in similar complexes, we examined the size of the 21-kDa chloroplast smHSP from Pisum sativum, PsHSP21, under non-denaturing conditions. Following sedimentation of chloroplast stromal extracts on sucrose gradients PsHSP21 is detected in fractions corresponding to 10-11 S. Upon non-denaturing gel electrophoresis, PsHSP21 was detected in two high molecular mass complexes of approximately 230 and 200 kDa, in good agreement with the sucrose gradient data. These PsHSP21-containing particles were stable under different salt and Mg2+ conditions, and their integrity was not affected by 1.0% Triton X-100 or 10 mM ATP. To study assembly of the high molecular weight complexes containing PsHSP21, in vitro translated PsHSP21 was imported into chloroplasts and its size was examined. Following import into chloroplasts isolated from heat-stressed plants, greater than 50% of PsHSP21 was recovered in the higher molecular weight forms. In contrast, following import into chloroplasts isolated from control plants the protein was recovered exclusively in a 5 S (approximately 42-kDa) form. These data suggest that preexisting PsHSP21 or other heat-induced factors may be required for assembly of the higher molecular weight particles. We propose that the 10-11 S particles are the functional form of PsHSP21.

Biological Transport↗
PubMed1994

Electron-deficient DNA-intercalating agents as antitumor drugs: aza analogues of the experimental clinical agent N-[2-(dimethylamino)ethyl]acridine-4-carboxamide.

A series of azaacridine (benzonaphthyridine) analogues of the drug N-[2-(dimethylamino)ethyl]-acridine-4-carboxamide (DACA) (currently in clinical trial) were synthesized. These compounds showed DNA binding affinities similar to that of DACA, as determined by the fluorometric ethidium displacement assay, but were generally less potent cytotoxins against P388 leukemia in vitro. The only compounds showing higher cytotoxicity than DACA were analogues with nitro substituents at the (acridine) 1-position; by analogy with the 1-nitroacridine nitracrine, these compounds probably undergo reductive metabolism. The only azaacridine to show significant in vivo antileukemic activity was benzo[b][1,5]naphthyridine-6-carboxamide. A possible reason for the unexpectedly low activity of these compounds (given the wide acceptability of substituents in DACA) may be their much lower lipophilicities, which are likely to result in lower rates of cell uptake.

Acridines↗
PubMed1994

Production of IL-10 by melanoma cells: examination of its role in immunosuppression mediated by melanoma.

Previous studies have shown that IL-10 may modulate immune responses towards the humoral arm by inhibiting production of cytokines involved in cell-mediated responses. In the present studies, we found that mRNA to IL-10 could be demonstrated in 66% of melanoma cell lines by PCR amplification of reverse-transcribed mRNA and in supernatants of the cell lines by ELISA. Release into the supernatants increased approximately 2-fold each day up to 3 days. The MW of 35S-labelled IL-10 secreted by melanoma cells was similar to that reported in previous studies. In the present studies we also examined whether IL-10 may be responsible for some of the immunosuppressive effects of the melanoma cell supernatants observed in previous studies, by testing whether MAbs against IL-10 could reverse the inhibitory effects of these supernatants. Recombinant IL-10 and melanoma supernatants were found to inhibit production of TNF-alpha, IFN-gamma, IL-2 and mixed lymphocyte reactions but reversal of these effects of melanoma supernatants by MAbs against IL-10 was only seen in the case of TNF-alpha production. These results extend the range of cell types known to produce IL-10 and indicate that malignancy of certain cell types may lead to unregulated production of IL-10 that could have the potential to modulate immune responses against the tumor.

Base Sequence↗
PubMed1994

Digestion of triacylglycerols containing long-chain polyenoic fatty acids in vitro by colipase-dependent pancreatic lipase and human milk bile salt-stimulated lipase.

To assess the role of human milk bile salt-stimulated lipase (BSSL) in the digestion of polyunsaturated ester bonds of triacylglycerols, hydrolysis of docosahexaenoic acid (22:6(n-3)) ester bonds was compared to that of oleic acid (18:1(n-9)) or arachidonic acid (20:4(n-6)) esters. As model substrates, we used rat chylomicrons obtained after feeding human milk fat globules and radiolabeled fatty acids. Radiolabeled chylomicrons were incubated with colipase-dependent pancreatic lipase, with BSSL, or with both enzymes in combination. Both enzymes hydrolyzed 18:1 more efficiently than 22:6 esters. With colipase-dependent lipase there was a large accumulation of 22:6 in diacylglycerol whereas with BSSL it accumulated mainly in monoacylglycerol. Esters containing 20:4 were hydrolyzed by BSSL as efficiently as 18:1 but this fatty acid also accumulated as diacylglycerol with colipase-dependent lipase. At low bile salt concentrations, as found in duodenal contents of newborns, colipase-dependent lipase was virtually unable to hydrolyze esters of 20:4 and 22:6 whereas BSSL hydrolyzed these esters at appreciable rates. Combining the two enzymes gave the most efficient hydrolysis of all fatty acids tested regardless of bile salt concentrations. BSSL may thus have a physiological role in completing duodenal hydrolysis of milk triacylglycerols containing 22:6- or 20:4-esters to free fatty acids and monoacylglycerol.

Arachidonic Acid↗