趋化因子CCL5表达与肾透明细胞癌病理特征及预后的相关性分析

目的:探讨趋化因子CCL5表达与肾透明细胞癌病理特征及预后的相关性分析。方法:回顾性分析2012年1月~2014年1月在某院肿瘤科治疗的100例肾透明细胞癌患者的临床资料,将其作为观察组,将同期100例健康体检者作为对照组,检测并比较两组的趋化因子CCL5水平,分析肾透明细胞癌组织及癌旁组织中CCL5表达的差异性、CCL5与肾透明细胞癌病理特征的关系、CCL5与肾透明细胞癌患者总体生存率的关系。结果:观察组CCL5水平明显高于对照组(P<0.05);肿瘤组织中CCL5表达阴性、弱阳性、中阳性、强阳性的比例与癌旁组织相比有明显差异(P<0.05);CCL5表达与肿瘤病理分期、肿瘤分级、肿瘤大小等密切相关,在分化低、级别高、直径大的肿瘤,CCL5表达越高(P<0.05),而与年龄、性别无显著关联(P>0.05);CCL5高表达的患者生存时间明显低于CCL5低表达的患者(P<0.05)。结论:趋化因子CCL5表达与肾透明细胞癌病理特征及预后有显著相关性,CCL5表达越高,病理恶性程度越高,预后越差,可作为临床评估病情严重程度的监测指标和潜在治疗靶点。     

环指蛋白180、p53及Ki-67在肾透明细胞癌中的表达及临床意义北大核心CSCD

目的研究环指蛋白180(RNF180)、p53及细胞增殖抗原标记物Ki-67在肾透明细胞癌(RCCC)组织中的表达水平及临床病理意义。方法收集225例确诊RCCC患者术后的石蜡标本及相应的远端正常组织制备组织芯片,用免疫组化法检测RNF180,p53和Ki-67在RCCC组织及癌旁组织的表达。结果在癌组织和癌旁组织中RNF180蛋白的阳性表达率分别为48.89%(110例/225例)和75.56%(170例/225例),p53蛋白的阳性表达率分别为45.71%(96例/210例)和2.38%(5例/210例),Ki-67蛋白的阳性表达率分别为32.20%(66例/205例)和2.44%(5例/205例),差异均有统计学意义(均P<0.05)。Spearman相关性分析显示,RNF180与p53及Ki-67均无相关性。Kaplan-Meier分析显示,RCCC患者的良好预后与RNF180的阳性表达呈正相关(P<0.05),而与p53及Ki-67无关。多因素Cox回归分析显示,TNM分期、肿瘤大小及RNF180是RCCC的独立预后因子。结论RNF180、p53及Ki-67可能分别参与RCCC的发生、发展过程,且RNF180可为RCCC患者预后提供参考。     

甲状腺乳头状癌组织中CD105的表达及其临床意义

目的 探讨甲状腺乳头状癌组织中CD105的表达及其临床意义.方法 应用免疫细胞化学SP法检测60例甲状腺乳头状癌存档蜡块标本中CD105的表达.同时检测正常甲状腺组织20例、良性甲状腺肿瘤30例标本作为对照.结果 正常甲状腺组织、良性甲状腺肿瘤标本50例,均无CD105的表达.甲状腺乳头状癌标本60例中41例CD105表达阳性,阳性率68.3%;其中有淋巴结转移的标本39例中34例(87.2%)阳性表达,无淋巴结转移的标本21例中7例(33.3%)阳性表达,二者比较,差异有统计学意义.结论 CD105在正常甲状腺组织、良性甲状腺组织的血管中无表达,在甲状腺乳头状癌组织中CD105呈高表达.CD105标记的微血管密度(MVD)值增高,是甲状腺乳头状癌病情进展和肿瘤转移的重要信号.CD105高表达,MVD值越高,肿瘤转移性越强,预后越差.CD105可以作为一项预测甲状腺乳头状癌潜在性转移的参考benwenj指标.     

甲状腺乳头状癌组织中CD105的表达及其临床意义

目的 探讨甲状腺乳头状癌组织中CD105的表达及其临床意义.方法 应用免疫细胞化学SP法检测60例甲状腺乳头状癌存档蜡块标本中CD105的表达.同时检测正常甲状腺组织20例、良性甲状腺肿瘤30例标本作为对照.结果 正常甲状腺组织、良性甲状腺肿瘤标本50例,均无CD105的表达.甲状腺乳头状癌标本60例中41例CD105表达阳性,阳性率68.3%;其中有淋巴结转移的标本39例中34例(87.2%)阳性表达,无淋巴结转移的标本21例中7例(33.3%)阳性表达,二者比较,差异有统计学意义.结论 CD105在正常甲状腺组织、良性甲状腺组织的血管中无表达,在甲状腺乳头状癌组织中CD105呈高表达.CD105标记的微血管密度(MVD)值增高,是甲状腺乳头状癌病情进展和肿瘤转移的重要信号.CD105高表达,MVD值越高,肿瘤转移性越强,预后越差.CD105可以作为一项预测甲状腺乳头状癌潜在性转移的参考benwenj指标.     

甲状腺乳头状癌组织中CD105的表达及其临床意义

目的 探讨甲状腺乳头状癌组织中CD105的表达及其临床意义.方法 应用免疫细胞化学SP法检测60例甲状腺乳头状癌存档蜡块标本中CD105的表达.同时检测正常甲状腺组织20例、良性甲状腺肿瘤30例标本作为对照.结果 正常甲状腺组织、良性甲状腺肿瘤标本50例,均无CD105的表达.甲状腺乳头状癌标本60例中41例CD105表达阳性,阳性率68.3%;其中有淋巴结转移的标本39例中34例(87.2%)阳性表达,无淋巴结转移的标本21例中7例(33.3%)阳性表达,二者比较,差异有统计学意义.结论 CD105在正常甲状腺组织、良性甲状腺组织的血管中无表达,在甲状腺乳头状癌组织中CD105呈高表达.CD105标记的微血管密度(MVD)值增高,是甲状腺乳头状癌病情进展和肿瘤转移的重要信号.CD105高表达,MVD值越高,肿瘤转移性越强,预后越差.CD105可以作为一项预测甲状腺乳头状癌潜在性转移的参考benwenj指标.     

甲状腺乳头状癌组织中CD105的表达及其临床意义

目的 探讨甲状腺乳头状癌组织中CD105的表达及其临床意义.方法 应用免疫细胞化学SP法检测60例甲状腺乳头状癌存档蜡块标本中CD105的表达.同时检测正常甲状腺组织20例、良性甲状腺肿瘤30例标本作为对照.结果 正常甲状腺组织、良性甲状腺肿瘤标本50例,均无CD105的表达.甲状腺乳头状癌标本60例中41例CD105表达阳性,阳性率68.3%;其中有淋巴结转移的标本39例中34例(87.2%)阳性表达,无淋巴结转移的标本21例中7例(33.3%)阳性表达,二者比较,差异有统计学意义.结论 CD105在正常甲状腺组织、良性甲状腺组织的血管中无表达,在甲状腺乳头状癌组织中CD105呈高表达.CD105标记的微血管密度(MVD)值增高,是甲状腺乳头状癌病情进展和肿瘤转移的重要信号.CD105高表达,MVD值越高,肿瘤转移性越强,预后越差.CD105可以作为一项预测甲状腺乳头状癌潜在性转移的参考benwenj指标.     

The determination and significance of CD105 positive cell in patients with primary hepatic carcinoma

目的 检测外周血CD105阳性细胞和甲胎蛋白(AFP)在原发性肝癌(HCC)患者的表达水平,探讨HCC患者与肝硬化患者及正常对照外周血CD105阳性细胞的差异及其临床意义.方法 选取住院HCC患者40例为HCC组,肝硬化患者60例为肝硬化组,30例健康志愿者为正常对照组.采用流式细胞术测定外周血CD105的阳性细胞比率,化学发光免疫法测定血清AFP.结果 HCC组外周血CD105阳性细胞水平高于肝硬化组与正常对照组(P<0.05),肝硬化组外周血CD105阳性细胞水平高于正常对照组(P<0.05);HCC患者的血清AFP的表达水平较肝硬化组和正常对照组升高(P<0.01),其中AFP>400 ng/ml的HCC患者外周血CD105阳性细胞水平显著高于AFP<400 ng/ml(P<0.01).结论 HCC患者外周血CD105阳性细胞水平较肝硬化患者和正常人群升高,AFP水平越高、肿瘤越大,CD105阳性细胞亦越多;外周血CD105阳性细胞的水平可作为临床HCC诊断指标之一.     

鼻内翻性乳头状瘤及其癌变中CD105和VEGF表达的研究

目的:通过研究鼻内翻性乳头状瘤(NIP)及其癌变中CD105和血管内皮生长因子(VEGF)的表达情况,探讨CD105和VEGF在NIP发生过程中的作用.方法:采用鼠抗人CD105和鼠抗人VEGF单克隆抗体,应用免疫组织化学技术检测31例NIP和12例鼻内翻性乳头状瘤癌变(NIP SCC)组织标本中的微血管密度(MVD)及VEGF的表达;并同时检测21例下鼻甲(IT)组织标本中的MVD及VEGF的表达作为对照研究.结果:(1)VEGF在IT、NIP、NSCC中的表达结果分别为(12.06±2.27)%、(42.99±11.45)%、(97.43±12.9)%,VEGF在NIP和NSCC中的表达,均显著高于下鼻甲组织,VEGF在NSCC的表达显著高于NIP,两两相比有显著性差异(P＜0.01).(2)CD105在IT、NIP、NSCC中的表达结果分别为2.08±0.37、6.43±1.93、26.4±8.23,CD105在NIP和NSCC中的表达,均显著高于下鼻甲组织,CD105在NSCC的表达显著高于NIP,两两相比有显著性差异(P＜0.01).(3)NIP中VEGF与CD105的表达呈显著正相关(r=0.604,P＜0.01).结论:CD105和VEGF在NIP中表达明显不同于在IT、NIP SCC中的表达且两者关系密切.因而可共同作为NIP中新生血管有价值的标记物,可以认为是与NIP生长、转移及预后有关的重要指标.     

CD105在胃癌中的表达及意义探讨

目的 检测胃癌患者中CD105的表达,探讨其在胃癌发生、发展及转移中的作用.方法 应用流式细胞术检测54例胃癌标本中CD105的表达,并与11例正常胃黏膜组织作对照.结果 CD105在胃癌组织中的表达量明显高于正常胃黏膜组织(P＜0.01);不同浸润深度、有无淋巴结转移的胃癌组织之间CD105表达差异均有统计学意义(P<0.05或P＜0.01).结论 CD105高表达与胃癌预后有关.     

原发性肝癌患者外周血CD105阳性细胞的测定及其意义

目的检测外周血CD105阳性细胞和甲胎蛋白(AFP)在原发性肝癌(HCC)患者的表达水平,探讨HCC患者与肝硬化患者及正常对照外周血CD105阳性细胞的差异及其临床意义。方法选取住院HCC患者40例为HCC组,肝硬化患者60例为肝硬化组,30例健康志愿者为正常对照组。采用流式细胞术测定外周血CD105的阳性细胞比率,化学发光免疫法测定血清AFP。结果 HCC组外周血CD105阳性细胞水平高于肝硬化组与正常对照组(P<0.05),肝硬化组外周血CD105阳性细胞水平高于正常对照组(P<0.05);HCC患者的血清AFP的表达水平较肝硬化组和正常对照组升高(P<0.01),其中AFP>400ng/ml的HCC患者外周血CD105阳性细胞水平显著高于AFP<400ng/ml(P<0.01)。结论 HCC患者外周血CD105阳性细胞水平较肝硬化患者和正常人群升高,AFP水平越高、肿瘤越大,CD105阳性细胞亦越多;外周血CD105阳性细胞的水平可作为临床HCC诊断指标之一。     

Pharmacokinetics of Pyrazinamide under Fasting Conditions,with Food,and with Antacids

Study Objectives . To determine intrasubject and intersubject variability in, and the effects of food and antacids on, the pharmacokinetics of pyrazinamide (PZA). Design . Randomized, four-period, crossover phase I study. Subjects . Fourteen healthy men and women volunteers. Interventions . Subjects ingested single doses of PZA 30 mg/kg under fasting conditions twice, without a high-fat meal and with an aluminum-magnesium antacid. They also received standard dosages of isoniazid, rifampin, and ethambutol. Measurements and Main Results . Serum was collected for 48 hours and assayed by gas chromatography with mass selective detector. Data were analyzed by noncompartmental methods and a compartmental analysis using nonparametric expectation maximization. Both fasting conditions produced similar results: mean PZA C_max 53.4 ± 10.4 μg/ml, T_max 1.43 ± 1.06 hours, and AUC_0-∞, 673 ± 79.7 μg·hr/ml. Fasting results are similar to those in previous reports. In the presence of antacids, subjects had a mean C_max of 55.6 ± 9.0 μg/ml, T_max of 1.43 ± 1.23 hours, and AUC_0-∞ of 628 ± 88.4 μg·hr/ml. In the presence of the high-fat meal, mean C_max was 45.6 ± 9.44 μg/ml, T_max 3.09 ± 1.74 hours, and AUC_0-∞ 687 ± 116 μg·hr/ml. Conclusions . These small changes in C_max. T_max, and AUC_0-∞. can be avoided by giving PZA on an empty stomach whenever possible. Conclusion : Serum concentrations in this study were consistent with those described previously. In addition, PZA's kinetic behavior was consistent between fasting treatments. Antacids and food had minimal effects on the agent's absorption. Samples drawn between 0.5 and 3 hours after dosing approached C_max for most subjects, with 1 hour being closest. Samples drawn as early as day 2 of daily PZA therapy will produce serum concentrations that approach steady-state values.     

Interactions of alkylureas with l-valine,l-valyl-l-valine,l-leucine,and l-leucyl-l-leucine

The solubilities of l -valine, l -leucine, l -valyl-l -valine, and l -leucyl-l -leucine have been determined in methyl-, N,N′-dimethyl-, and ethylurea solutions. Gibbs free energies of transfer of both amino acids and dipeptides as well as the peptide unit from water to alkylurea solutions have been ascertained. Enthalpies of transfer for the same compounds and the peptide unit have been determined from calorimetric measurements. The additivity principle for the contribution of the peptide unit and the side chains is obeyed neither for Gibbs free energy nor for the enthalpy of transfer. The most characteristic feature of Gibbs free energy data are the negative values for the transfer of the peptide unit to urea solutions and the positive values for the transfer to alkylurea solutions. Moreover, Gibbs free energy of transfer of the l -valyl and l -leucyl side chains is negative in alkylurea and urea solutions. The enthalpy of transfer values for urea solutions are generally negative, whereas the values for alkylurea solutions are positive. The enthalpy values for the l -valyl and l -leucyl side chains are positive as well. However, the enthalpy values for the peptide unit are all negative.     

Interaction of cimetidine with oxazepam, lorazepam, and flurazepam

The influence of cimetidine coadministration, 300 mg every 6 hours, on the kinetics of single oral doses of oxazepam (30 mg), lorazepam (2 mg), and flurazepam (30 mg) was evaluated in healthy volunteers. Cimetidine had no significant effect on the peak plasma concentration or the time of peak concentration for either oxazepam, lorazepam, or desalkylflurazepam (formed from flurazepam). Cimetidine likewise did not alter the elimination half-life of oxazepam (9.4 hours) or lorazepam (11.6 hours), and did not change total AUC for lorazepam. Oxazepam AUC was increased an average of 10 per cent by cimetidine (P less than 0.02). In contrast, cimetidine prolonged desalkylflurazepam elimination half-life (141 vs. 94 hours, P less than 0.1) and increased AUC an average of 65 per cent (P less than 0.05). Thus, cimetidine has little or no influence on the absorption or disposition of oxazepam and lorazepam, two benzodiazepines biotransformed by glucuronide conjugation. However, cimetidine slows the elimination of flurazepam's metabolite, desalkylflurazepam, which is biotransformed by oxidation.     

Interaction of oxaprozin with acetaminophen,cimetidine, and ranitidine

Summary Twelve healthy male volunteers participated in a single-dose four-way crossover study to evaluate potential drug interactions with oxaprozin, a nonsteroidal antiinflammatory agent of the propionic class. The four modes of administration were:a. oxaprozin, 1200 mg alone;b. oxaprozin during concurrent acetaminophen, 500 mg 4 times daily;c. oxaprozin with cimetidine, 300 mg 4 times daily;d. oxaprozin with ranitidine, 150 mg every 12 hours. Acetaminophen, cimetidine, or ranitidine were begun 24 hours prior to oxaprozin dosage and continued for the 10-day duration of each trial. No significant differences existed among the four treatment conditions in peak plasma oxaprozin concentration (86 µg/ml), volume of distribution (0.23 l/kg), time of peak concentration (3.7 h after dosage), or elimination half-life (54 h). Oxaprozin oral clearance was significantly lower (by 20%) during both the cimetidine and ranitidine trials versus control (0.047 vs 0.047 vs 0.059 ml/min/kg), but clearance during acetaminophen was not significantly different from control. Thus acetaminophen, cimetidine or ranitidine has only a small influence on the pharmacokinetics of a single oral dose of oxaprozin. The reduction in oxaprozin clearance due to cimetidine or ranitidine is statistically significant but small in magnitude.Supported in part by Grants MH-34223 and AG-00106 and Biomedical Research Support Grant RR-05598 from the USPHS, and by a Grant-in-Aid from Wyeth Laboratories, Radnor, PA, USA     

Effects of metoprolol, alone and in combination with lidocaine, on ventricular fibrillation threshold: comparison with atenolol, propranolol, and pindolol

Metoprolol and other beta-adrenergic blocking drugs are known to exert cardioprotective effects that include significant reduction in occurrence of ventricular fibrillation (VF) following myocardial ischemia and infarction. To help determine the mechanism of these cardioprotective effects, this study evaluated the effect of equipotent beta-blocking doses of metoprolol and three other beta-blockers with differing ancillary properties on ventricular fibrillation threshold (VFT) in the normal canine heart. Metoprolol tartrate (1.0 mg/kg i.v.), atenolol (0.3 mg/kg i.v.), propranolol hydrochloride (0.3 mg/kg i.v.), pindolol (0.03 mg/kg i.v.), or saline control (0.9% NaCl solution; vehicle) was given, alone and in combination with lidocaine (L), to groups of six pentobarbital (32.5 mg/kg i.v.) anesthetized mongrel dogs after control VFT and control isoproterenol-induced (ISO) positive chronotropic effects had been determined. The D- (membrane stabilizing, non-beta blocking) and L- (beta blocking) isomers of propranolol also were administered to separate groups of six anesthetized dogs in a dose of 0.3 mg/kg i.v. Blood samples (venous) were taken before drug or vehicle administration, 10 min after drug/vehicle administration and at half-hour intervals thereafter during experimentation. ISO responses and VFT were determined 5 and 15 min, respectively, after drug/vehicle administration and at half-hour intervals for a total experimental period of 165 min. VF was induced with a train of pulses (5 s, 100 Hz, 3-ms duration, 250-omega resistance) applied by bipolar platinum electrodes to a paced heart (200 beats/min). Voltage (V) was increased every 60 sec (0.25-V increments between 0-3.5 V and 0.5-V increments greater than 3.5 V) until VF occurred. Metoprolol increased VFT significantly (p less than 0.05) and maximally (max delta V = 2.3 +/- 0.7 V) at 135 min postdrug when the ISO-induced increase in heart rate was inhibited (%I ISO) by less than 53%. Max delta V was not significantly increased following i.v. administration of atenolol (0.8 +/- 0.6 V), pindolol (0.1 +/- 0.1 V), or saline (0.1 +/- 0.1 V). Max delta V was 0.5 +/- 0.2 in the D-propranolol-treated group and 0.5 +/- 0.3 in the L-propranolol-treated group. These values did not differ from max delta V obtained in the propranolol-treated group (0.6 +/- 0.4 V). Changes in VFT for all groups were, over time, negatively correlated with %I ISO and were not dependent on membrane stabilizing effect (metoprolol, propranolol (D,DL), pindolol), intrinsic sympathomimetic activity (pindolol), or cardioselectivity (metoprolol, atenolol).(ABSTRACT TRUNCATED AT 400 WORDS)     

Characteristics of patients with bulimia only, bulimia with affective disorder, and bulimia with substance abuse problems

Characteristics of patients with a diagnosis of bulimia only (N = 46), bulimia with a history of affective disorder (N = 34), and bulimia with a history of substance abuse (N = 34) were compared. Results showed that compared to patients with bulimia only or with bulimia and affective disorders, patients with bulimia and substance abuse experienced a higher rate of diuretic use to control weight, financial and work problems, stealing before and after the onset of the eating disorder, previous psychiatric inpatient treatment, and greater amount of alcohol use after the onset of the eating disorder. Both the substance abuse group and affective disorder group showed a higher incidence of attempted suicide, more social problems, and greater overall treatment rate than the bulimia only group. There were no significant differences among groups in their family histories.     

Rhytides, laxity, and photoaging treated with a combination of radiofrequency, diode laser, and pulsed light and assessed with a comprehensive grading scale

Several classes of nonablative laser and light technologies have been developed to target laxity, rhytides, and the various aspects of photoaging. The combination of the 3 main classes of nonablative rejuvenation, infrared laser, intense pulsed light, and radiofrequency energy, are assessed in the current study. Using a comprehensive grading scale developed to evaluate the multiple categories of the aging skin, quantitative analysis of changes in each category as well as overall improvement and patient satisfaction were calculated. The combination technology resulted in a patient mean (95% CI) percent improvement per category of 10.9% (8.1% to 13.7%) per treatment and 26% (16.5% to 35.5%) overall following a mean (+/- SD) of 2.4 (+/- 1.2) treatments. In addition, the patient satisfaction was 71.4%, suggesting that combining nonablative technologies may maximize clinical results and patient detection of improvement.     

Phenolic Cyclization of Epinephrine,Metaproterenol, Metaraminol,Phenylephrine, and Terbutaline with Formaldehyde

An exploratory study of the rates of cyclization of the title compounds, all 3-hydroxyphenalkanol-amines, with formaldehyde to 1,2,3,4-tetrahydroisoquinolines (THIQs) was performed using high-performance liquid chromatographic (HPLC) methods. Reactions occur quantitatively and practically instantaneously at room temperature and neutral pH; thus, rates were measured at acid pH. Cyclization occurs ortho or para to the 3-phenolic function, so that all but the 3,5-dihydroxyphenyl derivatives, metaproterenol and terbutaline, gave two THIQs. Terbutaline reacted significantly slower than the other compounds. Formaldehyde occurs in pharmaceutical systems and it serves as a model for other aldehydes that occur in sugars and flavors. The pharmaceutical implications of the reaction are discussed.