Development of acute autoimmune encephalomyelitis in mice: Factors regulating the effector phase of the disease

The development of acute experimental autoimmune encephalomyelitis (EAE) in mice is potentiated by the use of Bordetella pertussis vaccine as an adjuvant. Histamine sensitizing factor (HSF) extracted from B. pertussis is the active adjuvant agent and causes a mild increase in cerebrovascular permeability. During the development of EAE, there is an additional increase in vascular permeability of the brain and spinal cord. The adjuvant action of B. pertussis HSF does not appear to mimic a generalized beta-adrenergic blockade, since the course of EAE is not potentiated by adrenalectomy. The cerebrovascular permeability changes observed in EAE are probably mediated by vasoactive amines, since the expression of EAE can be blocked by vasoactive amine antagonists.     

Hypersensitivity pneumonitis in rabbits. Modulation of pulmonary inflammation by long-term aerosol challenge with antigen

Immunized rabbits that were aerosol challenged for 2 to 3 wk with pigeon dropping extract, an etiologic agent of hypersensitivity pneumonitis, developed chronic pulmonary inflammation associated with cell-mediated immunity in bronchoalveolar cells. However, prolonged aerosol challenge for 12 wk resulted in the diminution of pulmonary inflammation (modulation) and the loss of demonstrable cell-mediated immunity. This was probably not due to loss of sensitized lymphocytes that mediated pulmonary inflammation. Furthermore, rabbits undergoing modulation when they were challenged with an unrelated antigen were refractory to the development of pulmonary inflammation for at least 9 wk. After this refractory period, animals reimmunized and aerosol challenged with pigeon dropping extract displayed an anamnestic response and produced pulmonary lesions that were strikingly similar to the histopathology of human hypersensitivity pneumonitis.     

The thymus as primary site for antigen-specific T suppressor cells in neonatally induced tolerance to bovine serum albumin

The ontogeny of antigen-specific T suppressor cells in thymus and spleen was analyzed in CBA/Ca mice which were rendered tolerant as neonates by subimmunogenic doses of bovine serum albumin (low-zone tolerance). Activity of T suppressor cells from those mice was assessed by an assay in which spleen cells from animals primed with fluorescein-conjugated human gamma globulin can be stimulated in vitro to produce IgG anti-fluorescein antibodies when cultured in the presence of fluorescein-conjugated bovine serum albumin. Carrier-specific T suppressor cells appear first in the thymus (day 10), and much later (day 30) in the spleen. The data are discussed in connection with the possible role of T suppressor cells during induction of tolerance in newborn mice.     

Conjugation of DNA fragments to protein carriers by glutaraldehyde: immunogenicity of oligonucleotide-hemocyanin conjugates

The practical realization of the concept of specific immunotherapy for systemic lupus erythematosus (SLE) has been hampered, thus far, by an inability to link DNA fragments to carrier protein. In this paper, a novel technique is described, in which glutaraldehyde is the linking agent. A 2-stage method was used to link oligonucleotides to a soluble protein carrier, such as keyhole limpet hemocyanin (KLH) or human gamma globulin (HGG), whereas a 1-stage technique was sufficient to link oligonucleotides to sheep red cells. Both the ultraviolet absorbance spectrum and diphenylamine assay demonstrated that oligonucleotides were coupled to soluble protein. The conjugate of oligonucleotide to protein carrier appears to be recognized by anti-DNA antibody since oligonucleotide linked to either KLH or HGG inhibited the binding of anti-DNA antibody in vitro, and oligonucleotide-coupled sheep cells are agglutinating by seropositve sera from lupus patients. In addition, oligonucleotide-KLH raised hemagglutinating antibody to denatured DNA in C57BL/6, DBA/2 or NZB mice, as well as IgG antibody as detected by SPRIA in C57BL/6 and DBA/2 mice. The significance of this new method for the development of an antigen specific therapy of SLE is discussed.     

The filter technique for measuring leucocyte locomotion in vitro. Comparison of three modifications

Three forms of filter technique for measuring random and directional locomotion of leucocytes have been compared: (1) the conventional one filter technique of Boyden (lower surface count method); (2) the two filter system with a lower cell-impermeable filter designed to count the cells at the underside of the upper filter as well as those on the lower filter (two filter count method); and (3) two filter systems counting only cells associated with the lower filter (lower filter count method). In some instances all three methods produce qualitatively similar results. In others totally different results are reproducibly obtained with identical cell preparations, media and attractants. Compared to the two filter count method, the lower surface count method and the lower filter count method are not sufficiently reliable.The discrepancies are partly due to errors in measuring the response. They are caused by variable cell adhesion to the filters resulting in a varying distribution of cells between the upper and lower filter and/or detachment of neutrophils from the upper filter. Some of the discrepancies are not due to errors in assessing the response, but to differences in gradient formation and drift of chemokinetic and chemotactic materials from one compartment to the other.     

Quantitative effect of H-2-linked gene(s) on antibody response to human gamma-globulin

H-2-linked gene(s) have been found to play a role in the quantitative regulation of response to human gamma-globulin (HGG) in mice selected for high or low antibody responsiveness to sheep erythrocytes. Unexpectedly, in a random genetically heterogeneous population of F2 interline hybrids, the gene(s) linked to the H-2 phenotype of H mice has a "low" effect, and the gene(s) linked to the H-2 phenotype of L mice a "high" effect on the magnitude of antibody response to HGG. In H and L mice, the non-specific polygenic control of antibody responsiveness is able to compensate/counteract the inverse effect of HGG-specific H-2-linked gene(s) since the usual interline difference is observed.     

声带振动的二质量块-有限元模型

研究声带振动模型对揭示声带振动特性及理解声带振动的生理病理特征具有重要意义。本文结合非对称二质量块模型和有限元模型的优点,建立了声带振动的二质量块-有限元模型,并利用该模型实现了高速声门图的仿真。仿真结果表明,无论是正常声带的振动状态还是病理振动状态,输出结果都和实际声带振动特性相吻合。该模型为全面理解声带振动特性提供了一个崭新的工具     

替莫唑胺联合放疗治疗高级别脑胶质瘤的临床分析

目的 观察替莫唑胺(temozolomide, TMZ)联合放疗治疗高级别脑胶质瘤（high-grade glioma, HGG）患者的疗效和安全性,探讨影响HGG患者预后的因素。方法 回顾性分析50例采用TMZ联合放疗治疗初诊HGG患者临床资料。采用三维适形或调强放疗治疗,患者放疗期间均同步口服TMZ,剂量为75 mg/（m²·d） ;放化疗结束后,再行TMZ辅助化疗,方案为（150~200）mg/（m²·d）,连续服用5天,28天为1周期。观察患者的疗效及安全性,并对患者性别、年龄、KPS评分、手术切除程度、病理分级、手术至放疗开始间隔时间、放疗技术及TMZ辅助化疗周期数等因素对患者预后的影响进行多因素分析。结果 全组患者中位随访时间为21.4月（6.6~57.5月）,28例患者出现肿瘤进展或复发,22例患者死亡;全组1、2和3年总生存率（OS）和无进展生存率（PFS）分别为85.8%和71.8%、54.9%和44.2%及51.2%和44.2%。服用TMZ期间常见不良反应为恶心、呕吐,并伴有中性粒细胞及血小板的减少,但大多数患者均能耐受。多因素分析显示KPS评分、病理分级及辅助化疗周期数是影响OS的独立预后因素;手术切除程度、病理分级及辅助化疗周期数是影响PFS的独立预后因素。结论 TMZ联合放疗治疗初诊HGG疗效肯定,安全性较好。KPS评分、手术方式、病理分级及辅助化疗周期数是影响患者预后的重要预后因素。     

Plasma cells and their precursors. IV. Cross-reacting and non-cross-reacting, sheep erythrocyte lysing IgG antibody clones induced in rabbits immunized with rat- and chicken-erythrocytes

Rabbits were i.v. immunized with rat erythrocytes or chicken erythrocytes. The sera were investigated using the IEF technique. A number of the RRBC immunized animals and a high proportion of the CRBC immunized animals contained SRBC-lysing IgG antibody clones in addition to apparently normal anti-RRBC or anti-CRBC antibodies. Intravenous immunization with RRBC, followed by immunization with CRBC, yielded clones of SRBC-lysing IgG antibodies in almost every rabbit tested. By varying the interval between the RRBC- and CRBC injections, we established that the time needed for the RRBC-induced production of the responsible SRBC-specific IgG AFCP is approximately 5 days. These cells show an average functional half-life of 75 days. At least some of the RRBC- and CRBC-evoked SRBC-lysing IgG antibody clones are incapable of lysing either RRBC or CRBC. We suggest that the production of cross-reactive and non-cross-reactive, hetero-specific AFCP provides a natural explanation for the availability of preexistent AFCP responsible for the presence of the "early phase" of the IgG antibody response to several antigens.