Licensing and control authority batch release of influenza vaccine in Germany in accordance with EEC regulations

The epidemiological situation calls for almost yearly changes in the antigenic composition of influenza vaccine, thus necessitating fresh licensing procedures. Since the time for bringing a new vaccine onto the market should be relatively short, the following work of all parties involved must be done expeditiously: 1) WHO recommendations on new virus strains and their subsequent adaptation by the EEC (February/March); 2) Distribution of the new virus strains to the International Reference Centers for Influenza in the UK and USA (February/ March); the centers later issue reference materials for the determination of the haemagglutinin antigen concentration (April/May); 3) Production and testing of seed virus by manufacturers, as well as validation of the producer's inactivation process for the new virus strains (May/June); 4) Licensing of the vaccines by the National Control Authority (Paul-Ehrlich-Institute) (June/July); in the case of previously licensed products, the procedure is limited essentially to the approval of the detailed protocol of production and tests on the new virus strains, clinical studies not being required before licensing because of a lack of time; 5) Paul-Ehrlich-Institute's test for batch release, according to Directive 89/342/EEC, besides protocol approval, conducts material testing of the endotoxin and antigen content of each vaccine lot; the assay for the antigen quantification is especially laborious and sometimes must be repeated because of test invalidity.     

Corneal D.C. recordings of slow ocular potential changes such as the ERG c-wave and the light peak in clinical work

A set-up for D.C. recordings of slow ocular potentials such as the c-wave of the electroretinogram (ERG) as well as the fast oscillation (FO), the light peak (LP) and the dark trough (DT) in both clinical and experimental work is described. It includes matched calomel half-cells connected by saline-agar bridges to a corneal contact lens on the eye and a reference chamber on the forehead, a low-drift differential-input D.C. amplifier, an A/D converter, a computer, a thermoprinter, a flexible disc memory, a plotter, and a device for light stimulation controlled by the computer.Examples of the usefulness of the set-up in clinical work are shown in the form of D.C. c-wave ERGs of normal subjects as well as of patients with vitelliform macular degeneration, choriocapillaris atrophy, and retinitis pigmentosa. The direct corneal recording of the FO and LP is demonstrated as well. The different origins of the standing potential (SP) of the eye, the ERG c-wave, the FO and the LP are reviewed briefly.     

Peripancreatic lymphoadenopathy and extrahepatic immunological manifestations in chronic hepatitis C

Abstract. The aim of the study was to determine the role of peripancreatic lymph node swelling in systemic immunological alterations during chronic hepatitis C (HC). The prospective study was carried out as a clinical study in a university hospital. Clinical, haematochemical and ultrasonographic findings in 182 patients were studied. Ultrasonography was performed by the same operator and the findings were evaluated blind without the operator knowing the clinical and haematochemical parameters. Hepatitis B virus (HBV) markers, anti-HCV antibodies. LKMl, cryoglobulinaemia, rheumatoid factor and anti-tissue antibodies were determined. Liver biopsy was carried out in 43 of the 182 patients. One or two pathological peripancreatic lymph nodes (PLNs) were present in 30 of the 182 patients and, of the 30, 28 were anti-HC positive. Only one patient in the non-PLN group was positive for anti-HCV, there being statistical significance ( P <0.0001) between the PLN and non-PLN groups. In HCV-positive patients, extrahepatic immunological manifestations were observed (cryoglobulinaemia; positivity to anti-smooth muscle, antinuclear and antimitochondrial antibodies; positivity to rheumatoid factor and LKMl). In five patients the presence of focal lymphocytic aggregates was detected by biopsy, whereas one patient presented typical ocular lesion of Mikulicz's syndrome. Our results may confirm the marked lymphotropism shown by the HC virus and indicate more complex immune system involvement, especially in view of the coexisting signs of immune system involvement related to the presence of intrahepatic cellular aggregates detected in our study. We believe that the peripancreatic adenopathy in chronic HCV hepatitis is an important diagnostic sign and may indicate an involvement of the C virus in the still unexplained extrahepatic immunological disorders.     

维生素C浸泡羊膜对眼碱烧伤后移植的可用性研究

目的探讨维生素C浸泡羊膜的特性和生物活性物质的改变,以求为维生素C浸泡羊膜在眼碱烧伤羊膜移植中的合理应用提供依据。方法维生素C浸泡新鲜羊膜、保存1月羊膜,分别观察其大体物理特性、光学显微镜观察组织特性、免疫组织化学检测细胞因子的表达。结果维生素C浸泡羊膜与非浸泡羊膜的大体物理特性及光学显微镜观察组织特性无显著差别、部分细胞因子的活性表达无改变。结论维生素C浸泡羊膜不改变羊膜的组织学特性及部分细胞因子的活性,可以方便、安全地应用眼碱烧伤的移植治疗。     

Dendritic Cells Coinjected with Tumor Cells Treated with an Anticancer Drug to Induce Tumor Rejection

Purpose: We examined whether bone marrow-derived dendritic cells (DCs) could induce antitumor immunity when a chemotherapeutic drug was added. Methods: CT26 (a murine colon cancer cell line syngeneic with BALB/c) and CT26-bearing mice were treated with mitomycin C (MMC) intraperitoneally (i.p.). Next, mice immunized with a coinjection of DCs and MMC-treated CT26 (i.p.) were given an intradermal inoculation of CT26. Finally, CT26-bearing mice were treated with MMC (i.p.) with or without DCs, given peritumorally. Results: Although the inoculated tumor was not rejected in the control mice, CT26 was rejected in 50% of the mice injected with MMC alone. Apoptosis was observed in the MMC-treated CT26 cells in vitro and in vivo. Immunization with DCs and apoptotic CT26 cells, but not with apoptotic CT26 alone, gave protection against tumor challenge in 7 of 13 mice. A significantly higher level of cytotoxic T-cell activity and interferon-γ production was seen in the protected mice. When MMC (i.p.) treatment was followed by peritumoral DC injection in the CT26-bearing mice, remarkable therapeutic effects were observed. Conclusion: DCs can collaborate with chemotherapy-induced apoptotic tumor cells and elicit improved antitumor immunity, probably through the acquisition of tumor-associated antigens from apoptotic tumor cells. Received: January 7, 2002 / Accepted: September 3, 2002 Acknowledgments. We thank Dr. Kazuo Kinoshita for his useful advice on using flow cytometry. This research was partly supported by the Ministry of Education, Culture, Sports, Science and Technology (No. 11671160). Reprint requests to: S. Yamasaki     

Identification of neutrophil chemotactie factors in bronchoalveolar lavage fluid of asthmatic patients

Background Although neutrophils have been implicated in bronchial asthma, the mechanism(s) which bring these cells into the airways is poorly understood. Objective To investigate the presence and identity of neutrophil chemotactic factors in bronchoalveolar lavage (BAL) fluid from atopic asthmatic subjects. Method BAL fluid was obtained from 13 subjects (seven asthmatics and six normals). aged 19 to 60 yr, at bronchoscopy. Separation of neutrophil chemotactic activity (NCA) was achieved by FPLC cation exchange chromatography. Fractions were collected and assayed for chemotaxis multiwell micro-chemotaxes chambers using polycarbonate filters, for the complement peptide C5a/C5a des Arg by radioimmunoassay (RIA) and for interleukin-8 (IL-8) by ELISA. Results NCA was found in FPLC fractions of BAL samples in four out of seven asthmatics and each of these subjects had at least three similar peaks of NCA. The major peak of NCA was found to contain immunoreactive C5a/C5a des Arg and chemotaxis. In response to this NCA could be blocked by desensitization of the neutrophils with recombinant C5a. Purified serum derived C5a/C5a des Arg was found to have altered chromatographic properties when added to BAL fluid; this suggested that BAL fluid contained proteins which interacted with the C5a/C5a des Arg. Immunoreactive IL-8 (iIL-8) was also detected but its concentration or chemical form was insufficient to induce neutropbil chemotaxis. Conclusion This study demonstrates that bronchial asthmatic lavage fluid contains C5a/C5a des/Arg and iL-8, together with other as yet unidentified factors which may contribute to neutropbil recruitment in this disease.     

The effects of phorbol esters with different biological activities on protein kinase C

The sapintoxins are a series of naturally occurring fluorescent phorbol esters with a range of selective biological activities (e.g. pro-inflammatory but non-tumour promoting). Their ability to activate protein kinase C (PKC) in vitro has been studied. Both tumour promoting and non-promoting phorbol derivatives activate the enzyme in vitro at low concentrations. 12-deoxyphorbol-13-phenylacetate-20 acetate (DOPPA) acts as a partial agonist in the activation of protein kinase C. Structurally distinct phorbol esters may therefore preferentially activate different forms of protein kinase C. α-sapinine, a biologically inactive compound, binds to protein kinase C without stimulating the enzyme and prevents subsequent activation by phorbol esters such as 12-O-tetradecanoyl phorbol-13-acetate (TPA).     

Les formes psychiatriques de la maladie de Niemann-Pick de type C

Niemann-Pick type C disease diagnosed in adult neurology departments may be infantile or juvenile forms with prolongated life spans or forms starting at adolescence or adulthood. Psychomotor retardation is practically constant. In some cases, a psychosis may be the only manifestation for several years. The diagnosis is often made when extrapyramidal symptoms appear as well as cerebellar ataxia and ophtalmoplegia in the vertical gaze. The treatment with psychotropic drugs raises the question of a superimposition of a drug induced lipidosis. Hepatosplenomegaly is often discrete contrary to classical infantile cases. Foam cells as well as sea blue histiocytes are features of the disease. The filipin test evidences the lysosomal storage of cholesterol.     

人T淋巴母细胞（Jurkat）移动性的研究

利用人Ｔ淋巴母细胞（Ｊｕｒｋａｔ）细胞系作为研究对象。企图探探索细胞外基质成份及肌醇磷脂细胞信息传递系统与细胞移动的关系。研究结果表明：当细胞被伏波醇酯（ＰＭＡ）处理过后，其粘连性与移动件对纤维连结蛋白（ＦＮ）底物的反应在已是高水平的基础上有更进一步提高的作用。与ＦＮ刊相反的是，未经ＰＭＡ处理处的Ｊｕｒｋａｔ细胞对层粘连蛋白（Ｌｍ）底物却无明显的粘连性及移动性增加的反应，尽管在ＰＭＡ处理过４小时内亦无任何的增强。但是，当ＰＭＡ作用于细胞２４一４８小时后则明显池增加其Ｌｍ底物的粘连性及移动性反应，表明了其明显的协同作用。分别用抗ＦＮ、抗Ｌｍ及蛋白激酶Ｃ抑制剂Ｓｔａｕｒｏｓｐｒｉｎｅ（ＳＰ）时均起到特异性的抑制作用。可见，协同作用的产生是通过蛋白激酶Ｃ激活后的－段时间内，使细胞表面Ｌｍ受体密度增加而对底物Ｌｍ反应增强所致。