Defective Acidification in Human Breast Tumor Cells and Implications for Chemotherapy

Multidrug resistance (MDR) is a significant problem in the treatment of cancer. Chemotherapeutic drugs distribute through the cyto- and nucleoplasm of drug-sensitive cells but are excluded from the nucleus in drug-resistant cells, concentrating in cytoplasmic organelles. Weak base chemotherapeutic drugs (e.g., anthracyclines and vinca alkaloids) should concentrate in acidic organelles. This report presents a quantification of the pH for identified compartments of the MCF-7 human breast tumor cell line and demonstrates that (a) the chemotherapeutic Adriamycin concentrates in acidified organelles of drug-resistant but not drug-sensitive cells; (b) the lysosomes and recycling endosomes are not acidified in drug-sensitive cells; (c) the cytosol of drug-sensitive cells is 0.4 pH units more acidic than the cytosol of resistant cells; and (d) disrupting the acidification of the organelles of resistant cells with monensin, bafilomycin A1, or concanamycin A is sufficient to change the Adriamycin distribution to that found in drug-sensitive cells, rendering the cell vulnerable once again to chemotherapy. These results suggest that acidification of organelles is causally related to drug resistance and is consistent with the hypothesis that sequestration of drugs in acidic organelles and subsequent extrusion from the cell through the secretory pathways contribute to chemotherapeutic resistance.     

Comparison of salivary calmodulin binding proteins in Sjögren''s syndrome and healthy individuals

Background: Reduction in salivary secretion is the hallmark of Sjögren's syndrome (SS). Calmodulin (CaM) and calmodulin binding proteins (CaMBPs) play a key role in the secretory process of saliva. Recent studies have suggested that SS‐B, an autoantibody associated with SS, is a CaMBP. This finding suggests that CaMBP may contribute to the loss of saliva in SS. To better understand the role(s) of these proteins in SS, the purpose of this study was to compare salivary CaMBPs in Sjögren's patients and controls. Methods: Saliva samples were collected from 20 patients and 20 age‐, race‐, and gender‐matched controls. CaM overlay was used to identify CaMBPs in saliva of patients and controls. Results: Higher number of salivary CaMBPs was observed among patients than controls. Conclusions: The increased number of salivary CaMBPs in SS may suggest a potential role for these proteins in the pathogenesis of the disease.     

鞍区肿瘤术后中枢性低钠血症的诊断和治疗

目的:探讨鞍区肿瘤术后中枢性低钠血症的诊断及处理方法。方法:对我科近四年鞍区肿瘤术后并发中枢性低钠血症的58例患者进行回顾性分析,术前、手术当日及术后每日定时检测血钠,观察尿量变化,测定中心静脉压,确定低钠血症的类型并给予相应的处理。结果:56例恢复正常,1例死于严重肺部感染,1例自动出院。结论:鞍区肿瘤易出现抗利尿激素分泌不当综合症和脑性耗盐综合症两种类型。前者需限水治疗,后者应予以充分补钠、补水,根据水、钠检测水平治疗。     

数字化曲面全景X线系统造影在腮腺非肿瘤类疾病诊断中的应用

目的　本文报告普通X线机腮腺造影与数字化曲面X线机腮腺造影结果及其对比应用。方法　用3种不同的X线机对 3组腮腺非肿瘤类疾病患者进行腮腺造影 ,第 1组患者 10人应用普通 30 0mAX线机 ,第 2组患者 10人应用普通曲面全景X线机 ,第 3组患者 36人应用数字化曲面全景X线系统一套 ,分别行造影检查。结果腮腺造影侧位投照第 2组与第 1组末梢导管及腺泡有显著差异 (P <0 .0 5 ) ,第 3组与第 1组末梢导管及腺泡无显著差异 (P >0 .0 5 ) ,腮腺造影后前位投照第 2组与第 1、3组之间有显著差异 (P <0 .0 5 )。结论　本研究对比了 3种X线投照技术在腮腺非肿瘤性疾病造影诊断中的效果 ,用数字化曲面全景X线系统造影在诊断此类疾病中显示出较好的效果。     

沃辛瘤35例临床分析

目的：探讨沃辛瘤的发病及临床诊治特点。方法：对近10年来收治的35例经病理证实的沃辛瘤患者的临床资料进行统计分析。结景：肿瘤全部发生在腮腺。多见于50～70岁的男性，平均年龄56．9岁，男女之比为10．7：1。肿瘤位于腮腺后下极31例，占88．5％。同侧多灶性或双侧发生4例，占11．4％。吸烟者占全部病例71．4％(25例)。治疗采用全腮腺或浅叶 肿物切除术，无复发病例。诘论：腮腺后下部淋巴结与其中的迷走涎腺组织是肿瘤发生的组织学基础，吸烟和高龄免疫功能改变可能是肿瘤发生的主要刺激因素，采用肿瘤与不同范围腮腺组织切除术可达治愈效果。     

胰岛素泵治疗与2型糖尿病第一时相分泌的研究进展

随着对糖尿病机理研究的深入，发现胰岛β细胞第一时相分泌，对糖尿病的发生、发展有重要影响，新诊断2型糖尿病患者早期予胰岛素泵治疗，模拟生理性胰岛素分泌方式，可改善第一时相分泌，促进胰岛β细胞功能的修复，利于糖尿病的治疗及预后。     

成人肾上腺皮质癌的诊断和治疗(附16例报告)

目的：探讨成人肾上腺皮质癌的临床特点和治疗方法。方法：回顾性分析16例成人肾上腺皮质癌患者的临床资料，全部患者术前行B超、CT等影像学检查，10例接受内分泌激素检测，均首先行手术治疗，完整切除肿瘤13例，未能完整切除者3例。结果：术前13例明确诊断，3例末确诊。术后病理检查I期肿瘤3例，Ⅱ期9例，Ⅲ期4例。随访N一62个月，平均生存48个月；有5例至今生存，其中3例因术后转移而进展为Ⅳ期，行联合化疗(PDD加ADM加VN16)3—5周期，均末达到肿瘤缓解，术后平均生存17个月。3例末完全切除者术后放疗均末控，均因肿瘤扩散死亡，术后平均生存期为11个月。结论：成人肾上腺皮质癌恶性程度高，影像学检查是确诊的关键；早期发现并行根治性切除手术是目前提高其生存率的唯一有效方法。     

异体胸腺的解剖、组织学及吻合血管移植治疗晚期恶性骨肿瘤的研究

本文对20例20～36周引产死胎胸腺进行了解剖学,组织学观察,并应用吻合血管胎儿胸腺移植治疗晚期恶性原发及继发骨肿瘤12例。结果表明,胎儿胸腺的血供主要来自胸廓内动脉,其次为甲状腺下动脉和心包膈动脉胸腺支,7～8个月胎儿胸腺静脉血管壁较厚,适合作血管吻合,胸腺细胞发育成熟,组织结构正常,已有分泌胸腺素及转化免疫细胞的功能,在解剖学,组织学,免疫学方面均具备了良好的移植条件。12例接受吻合血管胎儿胸腺移植的晚期恶性骨肿瘤患者,其临床症状、体征、X线、免疫指数均有明显改善,患者生存6个月至37个月以上。     

附子对大鼠的抗炎作用

本研究结果表明附子煎剂对巴豆油所致小鼠耳部炎症,甲醛所致大鼠脚跖肿胀有显著抑制作用,切除双侧肾上腺的大鼠,附子煎剂对甲醛所致的足跖肿胀仍有明显抑制作用。提示附子具有抗炎症作用,且附子的抗炎症作用与肾上腺系统无明显关系。     

ENDOTHELIN RECEPTORS IN RAT ADRENAL GLAND VISUALIZED BY QUANTITATIVE AUTORADIOGRAPHY

1. The radioligand [125I]-endothelin was used to map receptors for endothelin in rat adrenal gland using in vitro autoradiography and computerized densitometry. 2. In the adrenal, a high density of binding was found in the adrenal medulla (binding affinity constant 0.18 +/- 0.11 X 10(9)M-1) and zona glomerulosa (binding affinity constant 0.18 +/- 0.07 X 10(9)M-1). Binding was low to undetectable in the zona fasciculata and zona reticularis. Unrelated peptides did not displace endothelin. 3. These results provide evidence of endothelin receptor distribution in adrenal gland and suggest that endothelin might exert multiple actions in the adrenal gland on catecholamine and aldosterone biosynthesis and secretion.