小鼠颅神经嵴细胞的培养和特征

目的：在体外原代培养Balb/c小鼠胚胎的颅神经嵴细胞。为颅面部各种组织细胞的发育研究提供细胞来源。方法：采用胰酶消化法分离小鼠胚胎第8.5天的颅神经管，从小鼠颅神经管中游离出来的细胞即为颅神经嵴细胞，用免疫组织化学方法鉴定细胞的来源，并测定细胞的生长曲线。结果：成功地培养出小鼠的颅神经嵴细胞，其形态类似成纤维样细胞，免疫组化检测结果表明，神经特异性烯醇化酶（NSE）抗体染色结果阳性。细胞的群体倍增时间为43.65h。结论：原代培养的小鼠颅神经嵴细胞生长稳定，来源明确，是颅面部各种细胞的发育和分化研究中一种有用的工具。     

Aging, retirement, and changes in physical activity: prospective cohort findings from the GLOBE study

There is increased recognition that determinants of health should be investigated in a life-course perspective. Retirement is a major transition in the life course and offers opportunities for changes in physical activity that may improve health in the aging population. The authors examined the effect of retirement on changes in physical activity in the GLOBE Study, a prospective cohort study known by the Dutch acronym for "Health and Living Conditions of the Population of Eindhoven and surroundings," 1991-2004. They followed respondents (n = 971) by postal questionnaire who were employed and aged 40-65 years in 1991 for 13 years, after which they were still employed (n = 287) or had retired (n = 684). Physical activity included 1) work-related transportation, 2) sports participation, and 3) nonsports leisure-time physical activity. Multinomial logistic regression analyses indicated that retirement was associated with a significantly higher odds for a decline in physical activity from work-related transportation (odds ratio (OR) = 3.03, 95% confidence interval (CI): 1.97, 4.65), adjusted for sex, age, marital status, chronic diseases, and education, compared with remaining employed. Retirement was not associated with an increase in sports participation (OR = 1.12, 95% CI: 0.71, 1.75) or nonsports leisure-time physical activity (OR = 0.80, 95% CI: 0.54, 1.19). In conclusion, retirement introduces a reduction in physical activity from work-related transportation that is not compensated for by an increase in sports participation or an increase in nonsports leisure-time physical activity.     

Treatment of progressive Hodgkin's disease with intensive chemoradiotherapy and autologous bone marrow transplantation

Twenty-six patients with progressive Hodgkin's disease after conventional chemotherapy received intensive chemoradiotherapy and autologous bone marrow transplantation (ABMT); 19 also received additional involved-field radiotherapy. Twenty-one patients [81%, 95% confidence intervals (CI) 61% to 94%] attained complete (n = 18) or partial responses. Ten patients (38%, 95% CI 20% to 59%) are disease- free a median of 4.5 years later (range 3.5 to 7.0 years), including seven patients with continuous complete responses. The likelihood of overall response was not significantly influenced by any clinical or treatment variable examined. However, there was a trend favoring patients with higher Karnofsky scores, and higher scores were associated with attainment of complete responses (P = .06 and P = .02, respectively, Mann-Whitney U test). Both higher Karnofsky scores and shorter durations of disease before transplantation were associated with improved survival in a stepwise Cox multivariate analysis. The chief cause of failure was progression at sites previously involved with Hodgkin's disease. No patient relapsed in the marrow, and two of three patients with a history of marrow involvement with Hodgkin's disease achieved durable complete responses after transplantation. These data suggest that inadequate pretransplant conditioning, and not the reinoculation of occult tumor cells in the autologous marrow, caused most relapses. Fatal treatment-related toxicity occurred in six patients. Three patients died of idiopathic interstitial pneumonitis; each had previously received local mediastinal irradiation before intensive chemoradiotherapy. Intensive chemoradiotherapy and ABMT produces durable responses in some patients with Hodgkin's disease incurable with conventional therapy. Use of such therapies at the first sign of failure with conventional chemotherapy and development of more effective conditioning regimens should further improve results.     

Differential expression of CD11b/CD18 (Mo1) and myeloperoxidase genes during myeloid differentiation

During the course of differentiation of early human myeloid cells toward monocytes and granulocytes, cell surface expression of the cell adhesion molecule, CD11b/CD18 (Mo1) increases dramatically and expression of myeloperoxidase (MPO), a bacteriocidal enzyme, decreases markedly. Using the inducible promyelocytic cell line HL-60 as a model, we studied the mRNA expression of these genes. Differentiation of these cells along both a monocytic and a granulocytic pathway demonstrated that the mRNA levels of the two subunits of CD11b/CD18 increased in a pattern temporally and quantitatively similar to the increase in cell surface expression of this heterodimer. In contrast, the expression of MPO mRNA decreased in a temporal and quantitative pattern similar to the known decrease in MPO protein during differentiation, suggesting that regulation of these myeloid-specific proteins may occur at the level of mRNA expression. These findings have important implications with regard to the nature of the block in differentiation in acute nonlymphocytic leukemia and the regulation of myeloid gene expression.     

Gold-induced pneumonitis

Gold-induced pneumonitis is a rare complication of gold salt therapy. We describe a patient with rheumatoid arthritis treated with gold salts, who developed bilateral interstitial pulmonary abnormalities and showed a dramatic response on corticosteroid therapy. Although after 4 weeks of treatment with corticosteroids the chest X-ray and lung function were still abnormal, bronchoalveolar lavage showed a normal cell distribution. Corticosteroid therapy was continued for 8 months since there was still improvement of pulmonary function studies. This case supports the view that in gold-induced pneumonitis a prolonged treatment with corticosteroids may be necessary, as lung function continued to improve.     

High-dose cytosine arabinoside and daunorubicin as consolidation therapy for acute nonlymphocytic leukemia in first remission: a pilot study

High-dose (HD) cytosine arabinoside (ARA-C) is more effective treatment than conventional-dose ARA-C regimens for patients with relapsed acute nonlymphocytic leukemia (ANLL). We report here that HD ARA-C given during the first remission of ANLL has resulted in long remission durations and a high proportion of patients who survive more than three years free of disease. From August 1979 to September 1983, 36 adult patients with ANLL in first remission received one to three courses of HD ARA-C (3 g/m2 by one-hour infusion every 12 hours for 12 doses on days 1 through 6) alone or with daunorubicin (30 mg/m2 for two or three doses on days 7 through 9). Three patients died of sepsis or hemorrhage during consolidation, and 14 patients have relapsed from five to 48 months after diagnosis. The remaining 19 patients are in continued complete remission (CCR) from 11 to 62 months. Denoting all deaths in remission as relapse, the actuarial probability of CCR is 42% at 62 months, with an apparent plateau in the survival curve. Of the first 22 patients treated, ten remain in CCR from 37 to 62 months with no therapy for at least three years. Due to its heightened anti-leukemic activity, HD ARA-C allows brief but effective consolidation of ANLL in first remission, with long-term disease-free survival comparable to other approaches.     

Relationship of the clinical response and binding of recombinant interferon alpha in patients with lymphoproliferative diseases

Patients with hairy cell leukemia (HCL) and chronic lymphocytic leukemia (CLL) were treated with recombinant interferon alpha A (rIFN- alpha A). The binding of iodinated recombinant interferon-alpha to baseline samples of peripheral blood mononuclear cells (PBMCs) from the leukemia patients was compared with clinical responsiveness to rIFN- alpha A. HCL patients (8/10) responded to rIFN-alpha A therapy, whereas none (0/10) of the CLL patients studied responded. The PBMCs from the eight responsive HCL patients bound approximately twice as much iodinated interferon as the PBMCs from nonresponsive CLL patients. This difference was due to more high-affinity receptors per cell with no difference in the affinity of the interferon-receptor interaction. However, because PBMCs from HCL patients were larger than PBMCs from CLL patients, the cell surface receptor density was similar. The leukemic cells from one of the two nonresponsive HCL patients bound iodinated interferon similarly to the cells from the responsive HCL patients, whereas the leukemic cells from the other nonresponsive HCL patient bound considerably less. The rapidity of response of the HCL patients did not correlate with the level of binding of iodinated interferon. Our results suggest that the absolute number of interferon receptors per cell may be only one of several important parameters in the response to rIFN-alpha A therapy, and that the responsiveness of a particular lymphoproliferative disease or a particular patient to rIFN- alpha A therapy cannot be predicted or explained solely by the degree of interaction between IFN and its cell surface receptor.     

大肠癌免疫组化表达与临床病理的关系

目的:探讨大肠癌CEA、P53、nm23、Ki-67、MRP免疫组化表达特点和相互关系,及其与临床病理的关系．方法:回顾性分析2003-01／2006-07我院收治的73例大肠癌患者的临床病理及随访资料,并对其石蜡标本采用免疫组化SP染色法检测CEA、P53、nm23、Ki-67、MRP,分析其免疫组化特点及其与临床病理之间的关系．结果:CEA、P53、nm23、Ki-67、MRP在大肠癌中的阳性表达率依次为82．2％、68．5％、75.3％、84．9％和64．4％．CEA、MRP与大肠癌患者的各因素无统计学差异．P53、Ki-67和nm23与肿瘤的Dukes分期和淋巴结转移有关, P53、Ki-67在Dukes C、D期的阳性表达率(依次为82．8％和100％1明显高于Dukes A、B期者(59．1％和75．0％)(P<0．05),而nm23在Dukes C、D期的阳性表达率(58．6％)明显低于Dukes A、B期者(86．4％)(P<0．05)．CEA与nm23的表达呈明显的负相关(r=-0．296,P=0．011),而P53和Ki-67表达之间呈现明显的正相关(r= 0．308,P=0．008),其他各指标间的表达无相关性．nm23、P53和Ki-67与预后因素关系明显,nm23在生存期≥3 a患者的阳性表达率(92．9%)高于生存期<3 a者(71．2％)(P<0．05),而P53和Ki-67在生存期≥3 a患者的阳性表达率(依次为42．9％和64.3％)明显低于生存期<3 a者(74．6％和89．8％)(P<0．05)．结论:P53、Ki-67和nm23的表达与大肠癌的侵袭转移和预后密切相关．CEA可能是大肠癌的侵袭转移的促进因素．MRP所引起的耐药机制是一个相对独立的机制．CEA、P53、nm23、Ki-67可作为判断大肠癌恶性程度、侵袭转移以及预后的指标．     

Bioequivalence of Liposome-Entrapped Paclitaxel Easy-To-Use (LEP-ETU) Formulation and Paclitaxel in Polyethoxylated Castor Oil: A Randomized,Two-Period Crossover Study in Patients With Advanced Cancer

Background

Preclinical studies comparing paclitaxel formulated with polyethoxylated castor oil with the sonicated formulation of liposome-entrapped paclitaxel (LEP) have demonstrated that LEP was associated with reduced toxicity while maintaining similar efficacy. Preliminary studies on the pharmacokinetics in patients support earlier preclinical data, which suggested that the LEP Easy-to-Use (LEP-ETU) formulation and paclitaxel formulated with castor oil may have comparable pharmacokinetic properties.

Objectives

Our objectives were: (1) to determine bioequivalence of paclitaxel pharmaceutically formulated as LEP-ETU (test) and paclitaxel formulated with castor oil (reference); and (2) to assess the tolerability of LEP-ETU following intravenous administration.

Methods

Patients with advanced cancer were studied in a randomized, 2-period crossover bioequivalence study. Patients received paclitaxel 175 mg/m² administered as an intravenous infusion over 180 minutes, either as a single-treatment cycle of the test formulation followed by a single-treatment cycle of the reference formulation, or vice versa.

Results

Thirty-two of 58 patients were evaluable and were included in the analysis for bioequivalence. Mean total paclitaxel C_max values for the test and reference formulations were 4955.0 and 5108.8 ng/mL, respectively. Corresponding AUC_0-∞ values were 15,853.8 and 18,550.8 ng·h/mL, respectively. Treatment ratios of the geometric means were 97% (90% CI, 91%–103%) for C_max and 84% (90% CI, 80%–90%) for AUC_0-∞. These results met the required 80% to 125% bioequivalence criteria. The most frequently reported adverse events after LEP-ETU administration were fatigue, alopecia, and myalgia.

Conclusion

At the studied dose regimen, LEP-ETU showed bioequivalence with paclitaxel formulated with polyethoxylated castor oil.