Outcome of B-cell non-Hodgkin lymphoma protocol CCCG-B NHL97: a report from Chinese multi-center cooperative group.
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Biomedical subjects
Publications and source records attributed to Jing Chen.
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A one-step phosphoryl derivatization method has been used in a peptide sequencing procedure for electrospray ionization tandem mass spectrometry (ESI-MS/MS). The sodiated derivatized peptides exhibit very simple dissociation patterns, in which two kinds of fragment ions, [b(n) + OH + Na]+ and [a(n) + Na]+, are formed. Since the amino acid residues are lost sequentially from the C-terminus, peptide sequences can be identified easily. The fragmentation efficiency of peptides increased as a result of the phosphorylation, and also provided peaks of useful intensity at lower m/z. A peptide with lysine at the C-terminus was derivatized and analyzed by ESI-MS/MS. Similar mass spectra, from which the sequence could be read out, were obtained. This is a novel derivatization method yielding neutral derivatives that should be suitable for peptide sequencing by LC/ESI-MS/MS.
The negative-ions of N-phosphoryl amino acids were studied by electrospray ionization tandem mass spectrometry (ESI-MS/MS). The negative-ion ESI-MS/MS of N-phosphoryl amino acids showed characteristic fragmentation patterns different from those observed in the corresponding positive-ion ESI-MS/MS and negative-ion fast-atom bombardment mass spectra. For negative-ion ESI-MS/MS, a unique fragmentation from the N-terminal of N-phosphoryl amino acids or peptides containing a free beta-OH or CO(2)H group was observed to yield the characteristic fragment ion (RO)(2)P(O)O(-). The ease of the rearrangement depended on the position of the hydroxyl group in amino acids or peptides, and the N --> O rearrangement mechanism was proposed to involve the participation of the hydroxyl group. From previous solution-phase experiments and theoretical calculations, it was found that the beta-OH group was more active than gamma-OH, and the corresponding difference in negative-ion ESI-MS/MS was consistent with those previous findings.
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Forty-eight older adults were tested on a battery of seven speeded visuospatial tasks that were developed by Chen et al. to measure the functions of the ventral and dorsal neural processing streams. Principal components analysis revealed only one factor with an eigenvalue greater than 1.0, and all of the tasks loaded heavily on this general factor. These results are in contrast to those reported in a previous study of young adults in which principal components analysis revealed two factors with eigenvalues greater than 1.0. Importantly, for young adults the second principal component was a bipolar factor which grouped the tasks based on the neural processing stream (i.e. ventral versus dorsal) whose function they had been designed to assess. The age-related difference in the factor structure of visuospatial abilities apparent from the present results may be interpreted as reflecting an age-related dedifferentiation of the neural processing streams consistent with the results of recent neuroimaging studies.
OBJECTIVE: The objective of this study was to explore our experience in the treatment of serious burn patients (total burn surface area [TBSA] > 90% and full thickness burns > 70% TBSA). METHODS: Thirty patients who were admitted to our unit over a period of 12 years were analyzed retrospectively; 23 cases (76.7%) were successfully treated. RESULTS: There were seven out of 12 cases (58.3%) in the first 5 years and 16 out of 18 cases (88.9%) in the latter 7 years of the study period. CONCLUSIONS: It is concluded that: 1) giving electrolyte-free fluids (around 3700 ml) and the maintenance of hourly urine output at 70 ml or more appear to be beneficial in resuscitation therapy; 2) the first operative procedure should be undertaken early, at about the third day after injury; 3) a higher percentage area of eschar to be excised in the first operation is encouraged and eschar excision of up to 40% or more is preferable; 4) controlling the area of exposed wound under 5% in the entire therapeutic course is essential in the prevention of burn infection; 5) emphasis should be placed on the vital role of a dehumidifier in reducing the incidence of fungal infection; and 6) early enteral nutrition with the use of growth hormone in correcting the nutritional state of the patient is also emphasized.
The phosphorylation of adenosine with trimetaphosphate in solution, in solid phase and using wet-dry cycles was carried out and it was found that wet-dry cycles were the most efficient. The catalytic effects of some metal ions on the phosphorylation were also studied and it was discovered that Ni(II) is the most effective. The combination of wet-dry cycles (4 cycles) and catalysis by Ni(II) led to an unprecedented high conversion of adenosine to phosphorylated products (30%) near neutral pH. The main phosphorylated products were 2',3'-cyclic AMP (10.4%) and 5'-ATP (13.0%).
Candida albicans had been thought to lack a mating process until the recent discovery of a mating type-like locus and mating between MTLa and MTL(alpha) strains. To elucidate the molecular mechanisms that regulate mating in C. albicans, we examined the function of Cph1 and its upstream mitogen-activated protein (MAP) kinase pathway in mating, as they are homologues of the pheromone-responsive MAP kinase pathway in Saccharomyces cerevisiae. We found that overexpressing CPH1 in MTLa, but not in MTLa/alpha strains, induced the transcription of orthologues of S. cerevisiae pheromone-induced genes and also increased mating efficiency. Furthermore, cph1 and hst7 mutants were completely defective in mating, and cst20 and cek1 mutants showed reduced mating efficiency, as in S. cerevisiae. The partial mating defect in cek1 results from the presence of a functionally redundant MAP kinase, Cek2. CEK2 complemented the mating defect of a fus3 kss1 mutant of S. cerevisiae and was expressed only in MTLa or MTL(alpha), but not in MTLa/alpha cell types. Moreover, a cek1 cek2 double mutant was completely defective in mating. Our data suggest that the conserved MAP kinase pathway regulates mating in C. albicans. We also observed that C. albicans mating efficiency was greatly affected by medium composition, indicating the potential involvement of nutrient-sensing pathways in mating in addition to the MAP kinase pathway.
The microvilli of the apical membrane of proximal tubule (PT) cells are supported by the underlying actin cytoskeleton. Ischaemic or anoxic ATP-depletion leads to the disruption of the actin cytoskeleton, resulting in microvillar retraction and loss of membrane polarity. Using isolated PT cells, we have previously demonstrated that actin filaments (F-actin) are likely severed during ATP-depletion. A sequential extraction protocol revealed a decrease in actin solubility, resulting in the sequestration of a distinct F-actin pool with the insoluble cellular complex in ATP-depleted PT cells. We demonstrate here that decreased actin solubility is not only a reliable end-marker of ATP-depletion induced injury in freshly isolated PT cells, but also serves as a biochemical marker in the cultured proximal tubular cell line LLC-PK1. In the present studies, we also investigated specific actin-binding drugs to determine if they mimic the effects observed during energy depletion. Jasplakinolide (JP), a compound which binds F-actin and prevents depolymerization, did not effect actin solubility during ATP-depletion. Furthermore, swinholide A (SA), an F-actin severing agent, resulted in decreased actin solubility, mimicking the effects of ATP-depletion. Interestingly, latrunculin A (LA), an agent which depolymerizes F-actin, did not reduce actin solubility, but rather resulted in an increase in digitonin-soluble actin. Taken collectively, our results support previous work and suggest that disruption of the actin cytoskeleton during ATP-depletion is mediated by F-actin severing/fragmentation and not depolymerization. The differential effects of F-actin disrupting agents and the consistencies observed in both models of ischaemic injury will provide a basis for a more detailed understanding of the pathological events of PT-cell dysfunction.
Several small clinical studies have reported that serum vitamin A levels were higher but serum vitamin C levels were lower among patients with end-stage renal disease. However, the relationship of antioxidant vitamins to renal function has not been studied in the general population. We examined the relationship of serum antioxidant vitamin levels to serum creatinine levels and risk for hypercreatininemia in a representative sample of 6,629 non-Hispanic whites, 4,411 non-Hispanic blacks, and 4,480 Mexican Americans aged 18 years or older who participated in the Third National Health and Nutrition Examination Survey. Serum antioxidant vitamins were measured by isocratic high-performance liquid chromatography, and serum creatinine levels, by the modified kinetic Jaffé method. Serum vitamin A level was positively and significantly associated with serum creatinine level, whereas serum vitamin C level was inversely and significantly associated with serum creatinine level. A one-SD higher level of serum vitamin A (16.9 microg/dL) was associated with a 2.53-fold (95% confidence interval, 1.96 to 3.27; P < 0.001), 2.07-fold (95% confidence interval, 1.84 to 2.33; P < 0.001), and 2.76-fold (95% confidence interval, 1.74 to 4.37; P < 0.001) greater risk for hypercreatininemia among non-Hispanic whites, non-Hispanic blacks, and Mexican Americans, respectively. A one-SD higher serum vitamin C level (0.45 mg/dL) was associated with a 22% (95% confidence interval, 0.06 to 0.35; P = 0.01) and 42% (95% confidence interval, 0.08 to 0.62; P = 0.02) lower risk for hypercreatininemia in non-Hispanic whites and Mexican Americans. Our study provides useful information to support the hypothesis that antioxidant vitamins may have an important role in the pathogenesis of chronic renal failure.
The extracellular matrix (ECM) plays an important role in cell differentiation and apoptosis. Collagen is the major component of ECM. Here, an ESR signal of the hydroxyl radicals (.OH) generated via Fe2+ -mediated Fenton reaction was found to be significantly inhibited by type I collagen. Further study showed that type I collagen also inhibited cell apoptosis induced by.OH, as evidenced by morphological criteria (DAPI and annexin V staining) and quantitive assays for apoptotic cells (MTT and flow-cytometric assay for subG1 cells). By addition of type I collagen in HeLa cells, the lipid peroxidation caused by.OH was inhibited and the cellular GSH was protected. In comparison with type I collagen, BSA and the denatured collagen, gelatin, lacked such antioxidative and antiapoptotic effects. Together, the results suggest that type I collagen can uniquely prevent.OH-mediated apoptosis by scavenging free radicals.
Gene vmrA, cloned from Vibrio parahaemolyticus, made Escherichia coli resistant to 4',6-diamino-2-phenylindol, tetraphenylphosphonium chloride, acriflavine, and ethidium bromide. VmrA belongs to the DinF branch of MATE family efflux transporters. VmrA catalyzed acriflavine efflux and showed Na(+)/drug transporter activity because the addition of tetraphenylphosphonium to Na(+)-loaded cells caused Na(+) efflux.
OBJECTIVE: To explore telomerase activity and its association with the proliferative potential of hematopoietic stem cells in bone marrow (BM) in patients with aplastic anemia (AA). METHODS: Telomerase activity of mononuclear cells separated from BM was determined with the TRAPeze kit. BM specimens from 22 cases with AA and 7 normal controls were included. SPSS10.0 was applied to analyze data derived from telomerase activity and colony-forming unit-granulocyte and monocyte. RESULTS: The median telomerase activity level of BM in AA was 2-fold higher than that in normal controls. There was an inverse correlation in AA between telomerase activity and colony-forming unit (r = 0.78, p < 0.05). BM of chronic AA expressed higher telomerase than that of acute AA. CONCLUSIONS: Telomerase activity in AA was increased and may be the result of the negative feedback of hematopoietic potential. Telomerase activity varied between the subtypes of AA. Telomerase activity was conversely correlated with the proliferative potential of BM in AA.
Serum vitamin C has been inversely associated with blood pressure in several epidemiologic studies, but little is known about effect of other antioxidant vitamins. We examined the relation between serum vitamins A, C, and E, alpha-carotene, and beta-carotene levels and blood pressure among 15 317 men and women > or =20 years of age who participated in the Third National Health and Nutrition Examination Survey. Blood pressure was characterized as the average of 6 measurements obtained over 2 visits by trained observers and hypertension was defined as blood pressure > or =140/90 mm Hg and/or taking antihypertensive medications. In multivariate models, a 1 SD difference in vitamin A (16.2 microg/dL) and vitamin E (20.4 microg/dL) was associated with a 43% (OR, 1.43; 95% CI, 1.34 to 1.53) and 18% (OR, 1.18; 95% CI, 1.09 to 1.27) higher odds of hypertension, respectively. A 1 SD difference in alpha-carotene (0.47 micro g/dL) and beta-carotene (496 microg/dL) was associated with a 16% (OR, 0.84; 95% CI, 0.76 to 0.94) and 11% (OR, 0.89; 95% CI, 0.82 to 0.97) lower odds of hypertension, respectively. In addition, serum vitamins A and E were positively and significantly associated with both systolic and diastolic blood pressure, whereas alpha-carotene and beta-carotene were inversely and significantly associated with systolic and vitamin C associated with diastolic blood pressure in multivariate linear regression analyses. These findings indicate that antioxidant vitamins may be important in the underlying cause and prevention of hypertension. Further studies in this important area are warranted.
The objective of this study was to estimate the prevalence and distribution of hypertension and to determine the status of hypertension awareness, treatment, and control in the general adult population in China. The International Collaborative Study of Cardiovascular Disease in ASIA (InterASIA), conducted in 2000-2001, used a multistage cluster sampling method to select a nationally representative sample. A total of 15 540 adults, age 35 to 74 years, were examined. Three blood pressure measurements were obtained by trained observers by use of a standardized mercury sphygmomanometer after a 5-minute sitting rest. Information on history of hypertension and use of antihypertensive medications was obtained by use of a standard questionnaire. Hypertension was defined as a mean systolic blood pressure > or =140 mm Hg, diastolic blood pressure > or =90 mm Hg, and/or use of antihypertensive medications. Overall, 27.2% of the Chinese adult population age 35 to 74 years, representing 129 824 000 persons, had hypertension. The age-specific prevalence of hypertension was 17.4%, 28.2%, 40.7%, and 47.3% in men and 10.7%, 26.8%, 38.9%, and 50.2% in women age 35 to 44 years, 45 to 54 years, 55 to 64 years, and 65 to 74 years, respectively. Among hypertensive patients, only 44.7% were aware of their high blood pressure, 28.2% were taking antihypertensive medication, and 8.1% achieved blood pressure control (<140/90 mm Hg). Our results indicate that hypertension is highly prevalent in China. The percentages of those with hypertension who are aware, treated, and controlled are unacceptably low. These results underscore the urgent need to develop national strategies to improve prevention, detection, and treatment of hypertension in China.
OBJECTIVE: To investigate the effect of IL-12 on the production of IFN-gamma and IL-4 by peripheral blood mononuclear cells (PBMC) from patients with tuberculosis. METHODS: PBMCs were isolated and cultured with RPMI 1640, PPD, PPD + rhIL-12, PPD + anti-IL-12, respectively. The level of IFN-gamma and IL-4 was detected with ELISA. RESULTS: Compared with the PPD group, IL-12 increased the production of IFN-gamma (321.6 +/- 87.7 vs 452.5 +/- 111.4, 387.0 +/- 70.8 vs 515.4 +/- 44.1, respectively), but decreased the production of IL-4 (54.6 +/- 11.0 vs 41.3 +/- 13.5, 55.1 +/- 9.5 vs 38.2 +/- 12.9, respectively) in the patients and the healthy individuals; anti-IL-12 blocked this effect. The level of IFN-gamma was lower in tuberculosis patients than that in the healthy controls. The IL-4 level was not different between the two groups (P > 0.05). The levels of IFN-gamma and IL-4 were lower in recurrent tuberculosis than those in the newly-diagnosed cases (P < 0.05). CONCLUSIONS: IL-12 induced IFN-gamma production and inhabited IL-4 expression, modulating the balance between TH(1) and TH(2) cytokines, suggesting that IL-12 enhances the host defense against tuberculous infection. IL-12 may be used for treatment of tuberculosis and vaccine development.
OBJECTIVE: To investigate the effects of the mixed endothelin receptor antagonist, bosentan, combined with the long-acting calcium channel blocker, amlodipine, compared to the angiotensin-converting enzyme inhibitor, cilazapril, on the progressive renal injury in spontaneous hypertensive rats (SHR) with diabetes. METHODS: Diabetic hypertensive rats (SHR-DM) were induced by streptozotozin injected in male SHR (7-week-old),and divided into an untreated and three treated groups: 1) cilazapril treated group; 2) bosentan+amlodipine treated group; and 3) amlodipine treated group. Wistar Kyoto rats (WKY) and SHR rats served as normotensive and hypertensive control, respectively. The mean arterial blood pressure, renal function, endothelin and angiotensin II levels as well as the protein expression of renal extracellular matrix components and transforming growth factor (TGF)-beta1 were determined at the end of the 4th week. RESULTS: Mean arterial blood pressure significantly increased in SHR and SHR-DM rats compared to WKY rats. All the therapies reduced the blood pressure to normal levels. However, the enhanced urinary protein excretion, the decreased creatinine clearance as well as the increased plasma and intrarenal endothelin and angiotens in II levels were found in the untreated SHR-DM and prevented by treatment with bosentan+amlodipine and cilazapril. Similarly, these two kinds of therapies in SHR-DM abolished the overexpression of renal TGF-beta1 by Western blot analysis and reduced the accumulation of collagen type IV, laminin and fibronectin proteins by an immunochemical approach. Amlodipine monotherapy had no detectable effects on the above parameters. CONCLUSION: Bosentan combined with amlodipine can offer similar renoprotective effects on that of cilazapril and may be a potent therapy to attenuate renal injury by reducing renal protein levels of TGF-beta1 in diabetes with a hypertensive state.
PURPOSE: These studies examined the effect of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor ZD1839 ("Iressa")(3) on CWR22 prostate tumors in nude mice. The effect of ZD1839 was also examined in combination with either bicalutamide ("Casodex") or cytotoxic agents against a hormone-dependent or -independent variant of CWR22, respectively. EXPERIMENTAL DESIGN: The xenografts were grown for 4-7 days, then tumor measurements were made and therapy initiated. ZD1839 and bicalutamide were given p.o. on a once-daily, 5-day schedule for 2 successive weeks. Carboplatin and paclitaxel were given every 3-4 days for a total of four doses. Measurements of tumor volume were made twice weekly during treatment and for 2 weeks after treatment. The effect of ZD1839 on EGFR function was assessed by Western blotting of EGFR and its phosphorylated form in CWR22 and variant tumors before and after treatment with this agent. RESULTS: ZD1839 at its maximum tolerated dose (150 mg/kg) inhibited the growth of androgen-dependent CWR22 by 54%, and the growth of two variants with different degrees of androgen independence and androgen receptor gene expression (CWR22LD1 and CWR22RV1) by 76%. The effects of ZD1839 were similar to those recorded for phosphorylation of EGFR as determined by Western blotting. Coadministration of ZD1839 at its maximum tolerated dose markedly increased the antiproliferative action of the antiandrogen bicalutamide against CWR22LD1. In fact, combining ZD1839 with a suboptimal dose of bicalutamide was more effective than a higher dose of bicalutamide alone. Coadministration of ZD1839, which required a 2-3-fold attenuation of dose to avoid toxicity, also markedly increased the therapeutic activity of carboplatin and paclitaxel against CWR22RV1, bringing about regression to a degree not seen with either agent alone. Tumor-free mice were seen only with the combination of ZD1839 and paclitaxel. CONCLUSIONS: The results obtained in these related and highly relevant models of human prostate cancer suggest that ZD1839 may have a role in enhancing existing treatments of androgen-dependent and -independent forms of this disease in patients.