Search for the possible role of ‘immunotherapy’ in operable bronchial non-small cell carcinoma (stage I and II): A phase I study with Corynebacterium parvum intrapleurally

Summary The possibility of giving C. parvum intrapleurally (i.p.) was investigated. C. parvum was given post-operatively either i.p. only or i.p. and intravenously (i.v.) simultaneously. The dose varied from 0.1–10 mg i.p. All patients had been operated for a bronchial carcinoma. Results: (1) Subjective complaints of either dyspnoea, thoracic pain, chills or nausea occured in 31 of 63 patients. No clear dose relation was found. A feeling of discomfort and fever could occur for another 3–4 days after the above more acute symptoms had disappeared. (2) Increased fever (0.5° C) occurred in 71% of the patients injected i.p. only. (3) No anaphylactic reaction was observed. (4) Increased total white blood cell counts (<20%) occurred in 38 patients. The WBC increase was mainly due to higher number of neutrocytes and granulocytes. Total lymphocyte, monocyte, eosinophilic, and basophilic granulocytes values per mm³ circulating blood remained unchanged, except at the dose of 7 mg C. parvum i.p. when monocyte values were increased significantly from 576±247 to 1100±578/mm³. (5) Moderate to severe effusions were observed radiologically in three patients after C. parvum intrapleurally.The study group is: M. Kaufmann, J. Stjernswärd (Ludwig Institut for Cancer Research, Lausanne Branch, Switzerland), M. Zelen, K. Stanley (Frontier Science and Technology Research Foundation, Inc. Amherst, New York, USA), D. S. Freestone, R. Bomford, M. T. Scott, T. Priestman (The Wellcome Research Laboratory, Beckenham, England), C. Mouritzen, G. Ahlbom (Dept. of Thoracic and Cardiovascular Surgery, Aarhus Kommunehospital, Aarhus, Denmark), N. Konietzko, D. Greschuchna (Ruhrland Klinic, Essen-Haidhausen, Germany), P. Hilgard (Innere Klinik und Poliklinik [Tumorforschung] Essen, Germany), J. Vogt-Moykopf, D. Zeidler, H. Toomes (Thoraxchirurgische Spezial-Klinik, Heidelberg-Rohrbach, Germany), F. Krause, R. Rios (Thoraxchirurgische Abt., Fachkrankenhaus für Lungen- und Bronchialerkrankungen, Löwenstein, Germany), J. Orel, M. Benedik, B. Hrabar (Clinical Center, Dept. of Thoracic Surgery, Ljubljana, Yugoslavia), S. Plesnicar (The Institute of Oncology, Ljubljana, Yugoslavia), H. A. Rostad, J. R. Vale (Rikshospital, Oslo, Norway), S. Hagen, S. Birkeland, (Ulleval Hospital, Oslo, Norway), T. Harbitz, R. Nissen-Meyer (Aker Hospital, Oslo, Norway), L. Rodriguez, V. O. Björk, K. Böök (Karolinska Sjukhuset, Thoracic Clinic, Stockholm, Sweden), E. Gradel, J. Hasse, P. Holbro (Kantonsspital, Thoraxchirurgische Klinik, Basel, Switzerland), L. Eckmann (Tiefenauspital, Chir. Univ.-Klinik, Bern, Switzerland), B. Nachbur, T. Liechti (Inselspital, Dept. of Thoracic and Cardiovascular Surgery, Bern, Switzerland), H. Cottier (Inst. of Pathology, Inselspital, Bern, Switzerland), W. Maurer, M. Kaufmann, P. Froelicher (Bürgerspital, Surgical Dept., Solothurn, Switzerland), H. Denck, N. Pridun (Krankenhaus der Stadt Wien-Lainz, Chir. Abt., Vienna, Austria), K. Karrer (Institute for Cancer Research, University of Vienna, Austria) Reprint requests should be addressed to any of the members listed above, or to the Ludwig Lung Cancer Trial, Operation Office, LICR, CH-1066 Epalinges, Switzerland. (For Current Contents, etc., please use above address)     

Stimulatory and inhibitory effects of dimethyl sulfoxide and ethylene glycol on ATPase activity and calcium transport of sarcoplasmic membranes.

1. The effect of dimethyl sulfoxide (Me2SO) and ethylene glycol on two different preparations of the sarcoplasmic reticulum, i.e. native membranes and membranes whose phospholipids were hydrolyzed by phospholipase A, were investigated using ATP and p-nitrophenylphosphate as substrates. 2. Me2SO and ethylene glycol inhibit both calcium-dependent ATP hydrolysis and ATP-supported calcium transport by native vesicles. 3. In contrast, calcium-dependent p-nitrophenylphosphatase activity as well as p-nitrophenyl-phosphate-supported calcium transport are activated by both agents at concentrations lower than 30% (v/v). 4. Me2SO strongly stimulates p-nitrophenylphosphate activity of vesicles treated with phospholipase A, but has relatively little effect on p-nitrophenylphosphatase activity of native vesicles. 5. Up to a concentration of approximately 40% Me2SO (v/v) the inhibiting effect on the calcium-dependent ATPase is fully reversible, but only partially reversible on calcium transport. 6. In the concentration range where Me2SO inhibits ATP hydrolysis and calcium transport, it does not affect ATP binding to the membranes nor calcium-dependent formation of phospho-protein. 7. The rate of dephosphorylation as well as the rate of Pi exchange between ATP and ADP are markedly reduced by the presence of 30% Me2SO (v/v). 8. While Me2SO inhibits passive calcium efflux, ethylene glycol produces a considerable activation. 9. ADP-dependent calcium efflux and ATP synthesis are activated by 15% Me2SO (v/v). Ethylene glycol reduces both activities. 10. The results suggest that the respective substrate-enzyme complexes are differently affected by the agents, resulting either in inhibition or stimulation     

Sterol and bile acid metabolism during development: 2. Identification of 3β-hydroxy-5-cholenoic acid (an intermediate in alternate pathway of bile acid synthesis) in newborn and fetal guinea pig

3β-hydroxy-5-cholenoic acid was found in the bile and feces of new-born and fetal guinea pigs. The identity of this compound was confirmed by gas chromatography and mass spectrometry. This finding suggests that the formation of chenodeoxycholic acid through 3β-hydroxy-5-cholenoic acid is intermediate in the early life of guinea pigs. Thus, it provides a useful model for studying the details of regulatory factors and significance of this pathway. This study also revealed that, unlike the adult guinea pig, the newborn guinea pig has significant amounts of glycine conjugates of bile acid.     

显微高速摄影技术及其在血液微流变学研究中的应用

本文选用金黄地鼠的微血管,利用显微高速摄影技术,放大微观流场和血细胞,连续地“冻结”短瞬间的变化状态,把物理图象呈现在胶片上,经图像分析和数据处理,从定性及定量方面研究血液微流变学,为生命科学和医学研究提供了又一种新的方法。     

The nascent polypeptide-associated complex (NAC) controls translation initiation in cis by recruiting nucleolin to the encoding mRNA

Protein aggregates and abnormal proteins are toxic and associated with neurodegenerative diseases. There are several mechanisms to help cells get rid of aggregates but little is known on how cells prevent aggregate-prone proteins from being synthesised. The EBNA1 of the Epstein-Barr virus (EBV) evades the immune system by suppressing its own mRNA translation initiation in order to minimize the production of antigenic peptides for the major histocompatibility (MHC) class I pathway. Here we show that the emerging peptide of the disordered glycine–alanine repeat (GAr) within EBNA1 dislodges the nascent polypeptide-associated complex (NAC) from the ribosome. This results in the recruitment of nucleolin to the GAr-encoding mRNA and suppression of mRNA translation initiation in cis. Suppressing NAC alpha (NACA) expression prevents nucleolin from binding to the GAr mRNA and overcomes GAr-mediated translation inhibition. Taken together, these observations suggest that EBNA1 exploits a nascent protein quality control pathway to regulate its own rate of synthesis that is based on sensing the nascent GAr peptide by NAC followed by the recruitment of nucleolin to the GAr-encoding RNA sequence.     

miR-10a Regulates Proliferation of Human Cardiomyocyte Progenitor Cells by Targeting GATA6

microRNAs (miRNAs) play essential roles in cardiogenesis. The altered expression of miRNAs can result in cardiac malformations by inducing abnormalities in the behavior of cardiac cells. However, the role of miR-10a in the regulation of cardiomyocyte progenitor cells (CMPCs) remains undetermined. In the present study, we found that up- or down-regulation of miR-10a inhibited or promoted the proliferation of human CMPCs, respectively, without affecting their differentiation toward cardiomyocytes. miR-10a bound to GATA6 directly and reduced GATA6 expression. Over-expression of GATA6 greatly attenuated the miR-10a-mediated inhibitory effect on the proliferation of human CMPCs. Thus, our results indicate that miR-10a could effectively modulate the proliferation of human CMPCs by targeting GATA6. The finding provides novel insights into the potency of miR-10a during heart development.     

半干旱黄土丘陵区纯林土壤腐殖质异化特征及与其他性质的关系

纯林长期生长或多代连栽必然会导致土壤腐殖质含量和构成发生异化,探究这种异化特征及其与土壤其他性质的关系可以为纯林管理或混交改造提供科学依据。通过对半干旱黄土丘陵区南泥湾林场8种典型纯林土壤腐殖质及其他性质进行系统检测,结果表明:(1)侧柏林土壤腐殖质含量最高(34.61 g/kg),腐殖化程度和稳定性一般;白榆和白桦林土壤的腐殖质含量中等(19.69—23.58 g/kg)、腐殖化程度和稳定性最佳;茶条槭和小叶杨林土壤的腐殖质含量(20.59—22.53 g/kg)和构成均为中等水平;油松、沙棘和刺槐林土壤的腐殖质质量较低(11.77—13.81 g/kg),且腐殖化程度较低,稳定性相对最差;(2)与胡敏酸含量存在显著相互促进作用(P0.05)的土壤性质为CEC、N、微生物量和蛋白酶活性(相关系数0.769—0.926,下同),存在显著相互抑制作用的为有效Cu(-0.793);与富啡酸存在显著相互促进作用的为N、CEC、微生物量、蔗糖酶和磷酸酶活性(0.836—0.955),存在显著相互抑制作用的为有效Cu(-0.822);与胡敏素存在显著相互促进作用的为N、CEC、微生物量、磷酸酶活性和有效Zn(0.766—0.951),存在显著相互抑制作用的为脱氢酶活性(-0.784)。(3)腐殖质构成与其他性质的相关性均不显著(P0.05),其中相对有利于提高胡敏酸/腐殖酸含量之比的土壤性质为蛋白酶、蔗糖酶和过氧化氢酶活性,而不利的是脱氢酶活性;相对有利于提高胡敏酸/富啡酸含量之比的为速效K、CEC和脲酶活性,而不利的是脱氢酶活性。(4)总体而言土壤腐殖质含量较之腐殖质构成与其他性质之间具有更大的相关性;向土壤增施N肥可以促进腐殖质的形成,增加K肥则有利于腐殖质构成的改善,而通过混交改造或增加林下植被是促进纯林土壤腐殖质化过程和解决土壤退化的根本措施。     

滇金丝猴（Rhinopithecusbieti）现状及其保护对策研究

滇金丝猴（Ｒｈｉｎｏｐｉｔｈｅｃｕｓｂｉｅｔｉ）是我国特有的珍稀濒危动物,生活在海拔３８００～４３００ｍ的原始冷杉林中,但有时也会在４３００～４７００ｍ的低矮灌丛、草甸和流石滩上活动达数小时之久,甚至能跨越近千米的无林高海拔地带,因而它们是海拔分布最高的非人灵长类。松萝是它们的主要食物,取食松萝的时间占总取食时间的９１％。猴群活动范围可达近百平方公里。笔者在历时８年的野外考察中,已查明这一物种的全部现存自然种群只有１３个,分布在云南的德钦、兰坪、潍西、丽江和西藏的芒康这五县境内,其现存种群数量为１０００～１５００只;所有现存自然种群几乎均处在相互隔离的状态,群间已不可能进行基因交流,充分表明它们已到达灭绝边缘。然而其栖息地内的商业伐木规模仍在继续扩大,周围的人口压力正在不断增加,各猴群均面临不同程度的偷猎压力。这一现状委实令人担忧。如何拯救这一“国宝”应引起我国保护学家和各级政府有关职能部门的重视