Appearance of retrogradely labeled neurons in the rat superior cervical ganglion after injection of wheat-germ agglutinin-horseradish peroxidase conjugate into the contralateral ganglion

Summary Injection of wheat-germ agglutinin-horseradish peroxidase conjugate (WGA-HRP) into the superior cervical ganglion (SCG) of the rat results in accumulation of WGA-HRP in sympathetic postganglionic neurons in the contralateral SCG. The sympathetic pathways involved and the mechanism underlying the labeling were investigated. The labeling in neurons in the contralateral SCG was apparent 6 h after injection and increased in intensity with longer survival times. The number of labeled neurons reached 1300 at 72 h after the injection. Transection of the external (ECN) or internal carotid nerves (ICN) resulted in considerable reduction in the number of labeled neurons. Combined transection of both ECN and ICN virtually eliminated labeling in the contralateral SCG. This provides strong evidence that these two nerves are the major pathways for WGA-HRP transport out of the SCG. No labeling was observed in the contralateral SCG following injection of horseradish peroxidase (HRP). Therefore, it seems unlikely that a direct nerve connection exists between the bilateral ganglia. Instead, the labeling of contralateral SCG neurons appears to depend on the transneuronal transport capacity of WGA-HRP, which conveys the marker in an anterograde direction along the postganglionic fibers to terminals in sympathetic target organs, and then delivers it transneuronally to contralateral SCG neurons. We suggest that the sympathetic nerve fibers originating in the bilateral SCGs run intermingled and are in close contact in their peripheral target organs.     

豚鼠肠系膜下神经节细胞电活动与结肠运动的关系

在豚鼠肠系膜下神经节(IMG)及其支配的结肠段联合标本上,对IMG细胞内电位与肠段纵肌或环肌舒缩活动进行了同步记录。实验结果表明:(1)肠段预置张力为零时,约50％IMG细胞有自发的快兴奋性突触后电位(EPSP)活动,切断结肠神经或以筒箭毒(50μmol/L)灌流IMG后消失;(2)筒箭毒或低钙高镁溶液阻断神经节传递时,环肌节律性收缩幅度增大,节律变慢,但对纵肌节律性收缩无明显影响,(3)串刺激节前神经,在IMG细胞引起一串快EPSP或动作电位并常跟随迟慢的EPSP,同时,纵肌在0.1-0.2s潜伏期后出现迅速的、时程基本与动作电位串一致的舒张波,后者在筒箭毒灌流IMG后消失,而环肌运动可见舒张、舒张波延长或收缩波增大。结果提示:IMG不仅中继经典的胆碱能传出功能,还参与以胆碱能传递为中介的肠-肠反射,该反射活动的传出效应主要在于抑制环肌收缩。     

抗胃癌细胞系单克隆抗体PD4的初步研究

以胃癌细胞系MGC803免疫Balb/c小鼠,取其脾细胞与小鼠骨髓瘤细胞NS-1融合。经选择培养、筛选及克隆化,获得恒定地分泌抗胃癌细胞系单克隆抗体(MoAb)的杂交瘤细胞系PD4。MoAb PD4与3/4胃癌细胞系有强结合反应,与4/4肺癌细胞系有弱结合反应,但与淋巴细胞、ABO红细胞、骨髓细胞、二倍体成纤维细胞及经检测的其他肿瘤细胞均无反应。PD4抗原主要表达于靶细胞的膜上,不耐热,为分子量40kD的蛋白性抗原。该抗原与HLA抗原系统,血型抗原系统无关,亦不同于其他作者所报告的其他胃癌相关抗原。     

Intrapleural and intravenous Corynebacterium parvum in patients with resected stage I and II non-small cell carcinoma of the lung

Summary A prospective randomized trial compared the administration of intrapleural plus intravenous Corynebacterium parvum (C. parvum) versus placebo in patients with resected Stage I and Stage II non-small cell bronchogenic carcinoma. Treatment consisted of 7 mg C. parvum injected into the pleural space and 7 mg C. parvum intravenously once between days 6 and 12 postoperatively and 7 mg intravenously every 3rd month during the 1st year. Intrapleural administration of 35 cc of saline served as the placebo and the flush after intrapleural C. parvum.Of the 303 patients entered into this study, 286 were evaluable, with an average follow-up time of 3.5 years. More complications, especially fever, were observed in patients receiving C. parvum. A fever greater than 38 °C was observed in 9% of the patients assigned to placebo and 76% of the patients assigned to C. parvum. There was no significant difference between the treatments with respect to disease-free interval or survival.M. Kaufmann, J. Stjernswärd**, A. Zimmermann (Ludwig Institute for Cancer Research, Bern Branch); K. Stanley**, M. Isley, M. Zelen (Frontier Science & Tech. Research Foundation, Brookline, MA, USA); C. Mouritzen, P. Paulsen, U. Henriques (Dept. of Thoracic and Cardiovascular Surgery and Institute of Pathology, Kommunehospital, Aarhus, Denmark); N. Konietzko, W. Maassen, W. Hartung, W. Wierich (Ruhrland Clinic, Essen-Heidhausen, and Pathology Institute, Ruhr-University, Bochum, FRG); P. Oehl (Innere Klinik und Poliklinik Tumorforschung, Essen, FRG); J. Vogt-Moykopf, H. Toomes, W. Hofmann (Rohrbach Hospital, Clinic for Thoracic Medicine and Pathology Institute, Heidelberg, FRG); F. Krause, R. Rios, R. Spanel (Klinik Löwenstein, Löwenstein, and Pathology Institute, Ulm, FRG); J. Orel, B. Hrabar, D. Ferluga, T. Rott (University Medical Center, Thoracic Surgery and Pathology, Ljubljana, Yugoslavia); H. A. Rostad, J. R. Vale, P. Lexow (Rikshospital, Oslo, Norway); S. Hagen, S. Birkeland (Ulleval Hospital, Oslo, Norway); T. Harbitz, R. Nissen-Meyer (Aker Hospital, Oslo, Norway); E. Aspevik, H. Engedal, A. Mykin (Haukeland Hospital, Bergen, Norway); V. O. Björk, L. Rodriguez, K. Böök, J. Willems (Karolinska Sjukhuset, Thoracic Surgical Clinic and Pathology Department, Stockholm, Sweden); E. Grädel, J. Hasse, P. Dalquen (Kantonsspital, Dept of Surgery, Div. of Cardiac & Thoracic Surgery & Pathology Institute, Basel, Switzerland); L. Eckmann, K. Hänni, K. Zimmermann (Tiefenauspital Surg. Clinic, Univ. of Bern, Switzerland); B. Nachbur, H. U. Würsten, H. Cottier, A. Zimmermann (Inselspital Dept. of Thoracic and Cardiovascular Surg. and Pathology Institute, Bern, Switzerland); W. Maurer, M. Kaufmann (Bürgerspital, Surgical Department, Solothurn, Switzerland); H. Denck, E. Zwintz, St. Wuketich (Krankenhaus der Stadt Wien-Lainz, I. Chir. Dept., and Path. Inst., Vienna, Austria); N. Pridun, H. Hackl (Pulmonologisches Zentrum der Stadt Wien, and Path. Inst., Vienna, Austria); E. Moritz, W. Schlick, H. Holzner (II. Chir. University Clinic and Path. Inst., Vienna, Austria); K. Karrer (Institute for Cancer Research, Vienna, Austria); R. G. Crispen (ITR-Biomedical Research, University of Illinois, Chicago, USA); D. S. Freestone, R. Bomford, M. T. Scott, T. Priestman, L. Toy (The Wellcome Research Laboratories, Beckenham, England)** Present address: Cancer Unit, World Health Organization, Geneva, Switzerland Offprint requests to: K. Stanley, Ludwig Institute for Cancer Research, Inselspital, CH-3010 Bern, SwitzerlandLudwig Lung Cancer Study Group:     

Construction and packaging of pseudotype retrovirus containing human N—ras cDNA antisense sequence and its biological effects on human hepatoma cells

N-ras is one of the transforming genes in human hepatic cancer cells.It has been found that N-ras was overexpressed at the mRNA and protein level in hepatoma cells.In order to explore the biological roles of N-ras in human hepatic carcinogenesis and the potential application in control of cancer cell growth,a preudotype retrovirus containing antisense sequence of human N-ras was constructed and packaged.A recombinant retrovirus vector containing antisense or sense sequences of N-ras cDNA was constructed by pZIP-NeoSV(X)1.The pseudotype virus was packaged ang rescued by transfection and infection in PA317 and ψ 2 helper cells.It has been demonstrated that the pseudotype retrovirus containing antisense N-ras sequence did inhibit the growth of human PLC/PRF/5 hepatoma cells accompanied with inhibition of p21 expression,while the retrovirus containing sense sequence had none.The pseudotype virus had no effect on human diploid fibroblasts.     

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)     

Loss to Clinic and Five-Year Mortality among HIV-Infected Antiretroviral Therapy Initiators

Missing outcome data due to loss to follow-up occurs frequently in clinical cohort studies of HIV-infected patients. Censoring patients when they become lost can produce inaccurate results if the risk of the outcome among the censored patients differs from the risk of the outcome among patients remaining under observation. We examine whether patients who are considered lost to follow up are at increased risk of mortality compared to those who remain under observation. Patients from the US Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) who newly initiated combination antiretroviral therapy between January 1, 1998 and December 31, 2009 and survived for at least one year were included in the study. Mortality information was available for all participants regardless of continued observation in the CNICS. We compare mortality between patients retained in the cohort and those lost-to-clinic, as commonly defined by a 12-month gap in care. Patients who were considered lost-to-clinic had modestly elevated mortality compared to patients who remained under observation after 5 years (risk ratio (RR): 1.2; 95% CI: 0.9, 1.5). Results were similar after redefining loss-to-clinic as 6 months (RR: 1.0; 95% CI: 0.8, 1.3) or 18 months (RR: 1.2; 95% CI: 0.8, 1.6) without a documented clinic visit. The small increase in mortality associated with becoming lost to clinic suggests that these patients were not lost to care, rather they likely transitioned to care at a facility outside the study. The modestly higher mortality among patients who were lost-to-clinic implies that when we necessarily censor these patients in studies of time-varying exposures, we are likely to incur at most a modest selection bias.     

Epistatic Gene-Based Interaction Analyses for Glaucoma in eMERGE and NEIGHBOR Consortium

Primary open angle glaucoma (POAG) is a complex disease and is one of the major leading causes of blindness worldwide. Genome-wide association studies have successfully identified several common variants associated with glaucoma; however, most of these variants only explain a small proportion of the genetic risk. Apart from the standard approach to identify main effects of variants across the genome, it is believed that gene-gene interactions can help elucidate part of the missing heritability by allowing for the test of interactions between genetic variants to mimic the complex nature of biology. To explain the etiology of glaucoma, we first performed a genome-wide association study (GWAS) on glaucoma case-control samples obtained from electronic medical records (EMR) to establish the utility of EMR data in detecting non-spurious and relevant associations; this analysis was aimed at confirming already known associations with glaucoma and validating the EMR derived glaucoma phenotype. Our findings from GWAS suggest consistent evidence of several known associations in POAG. We then performed an interaction analysis for variants found to be marginally associated with glaucoma (SNPs with main effect p-value <0.01) and observed interesting findings in the electronic MEdical Records and GEnomics Network (eMERGE) network dataset. Genes from the top epistatic interactions from eMERGE data (Likelihood Ratio Test i.e. LRT p-value <1e-05) were then tested for replication in the NEIGHBOR consortium dataset. To replicate our findings, we performed a gene-based SNP-SNP interaction analysis in NEIGHBOR and observed significant gene-gene interactions (p-value <0.001) among the top 17 gene-gene models identified in the discovery phase. Variants from gene-gene interaction analysis that we found to be associated with POAG explain 3.5% of additional genetic variance in eMERGE dataset above what is explained by the SNPs in genes that are replicated from previous GWAS studies (which was only 2.1% variance explained in eMERGE dataset); in the NEIGHBOR dataset, adding replicated SNPs from gene-gene interaction analysis explain 3.4% of total variance whereas GWAS SNPs alone explain only 2.8% of variance. Exploring gene-gene interactions may provide additional insights into many complex traits when explored in properly designed and powered association studies.