Aggregated IgE mimic interleukin-3-induced histamine synthesis by murine hematopoietic progenitors

Similar to interleukin-3 (IL-3), IgE acts on murine bone marrow cells by inducing histamine production. This effect does not result from degranulation of histamine-containing cells, but from histamine synthesis, as assessed by the following findings. (1) The histamine content of freshly isolated bone marrow cells is too low to account for the increase in extracellular histamine levels. (2) Neither IL-3 nor IgE induced histamine production in the presence of the specific inhibitor of histidine decarboxylase (HDC), the histamine-forming enzyme. (3) Both the enzymatic activity and the mRNA expression of HDC were enhanced in response to IL-3 or IgE. Artificial aggregation or formation of IgE immune complexes augmented ther effect on histamine synthesis, indicating that the aggregated form is responsible for this biologic activity. Yet, it is apparently not mediated by Fc epsilon RI because their cross-linkage by dinitrophenyl bovine serum albumin after presensitization with IgE did not induce histamine production by hematopoietic progenitors. Among other aggregated isotypes tested, only IgG2a and, to a lesser extent, IgG1 had a consistent but lower effect, whereas IgM and IgA were completely inactive. The target cells of IL-3 and IgE in terms of histamine synthesis do not belong to mature bone marrow populations, especially mast cells. They copurify with hematopoietic progenitors in the low-density layers of a discontinuous Ficoll gradient where they represent around 5% of the cells, as determined by in situ hybridization. This percentage remained the same, regardless of whether the cells were stimulated by IgE or IL-3 alone or by a combination of both, suggesting a common responder cell. In accordance with this notion, histamine-producing cells could not be distinguished from each other on the basis of density, size and internal structure, or rhodamine (Rh) retention. Finally, the effect of IgE is not caused by the induction of IL-3 because anti-IL-3 antibodies did not abrogate the effect of IgE.     

基于受体结构的药物分子设计系统:维甲类分子与其结合蛋白之间相互作用的研究

大分子解剖程序,配体分子契合适配和DOCK程序,以及计算化学的其它程序等,已集成为基于受体结构和分子间相互作用的进行分子设计的软件系统,定名为BIOS(Biomolecularinteractionsandorientationsimulator)。BIOS软件可在普通的微机上运行。使用BIOS分别剥离了细胞浆维甲结合蛋白(CRBP)和副睾维甲酸结合蛋白(E-RABP)两种蛋白的配体结合腔,剥离是围绕配体以同样的分子距离进行的。从而得到了芳香性残基分布相似的两个结合腔,其结合位点的几何排布却有相当差别。揭示出的结合腔已用于一系列的维甲类化合物的DOCK研究。E-RABP的结合腔可做为设计新维甲类分子的模板。     

An analysis of foot-and-mouth-disease epidemics in the UK

There was a major epidemic of the foot-and-mouth-disease virusamong cattle herds in the UK in 1967–68 which showed avery rapid early spread, a much slower later spread, and eventuallyinfected 12% of herds in the core epidemic area. A simple discrete-timeversion of a susceptible-latent-infectious-removed epidemiologicalmodel is used to generate a set of estimates of the transmissionrate. This parameter has high values over the first few days,then the values are lower and they subsequently decline. Theearly high values are consistent with the view that unusualmeteorological conditions produced exceptionally good conditionsfor wind-borne spread of the virus over the first few days.The corresponding basic reproduction number, R₀, is estimatedas 38.4. Subsequent low values of the transmission rate correspondto a value of R₀ of 2.0; this is within the range of estimatesmade from the observed ratio of secondary to primary outbreaksfor 25 other epidemics. Prophylactic control measures, suchas vaccination, would have to be extremely effective to preventepidemics with the higher R₀ value.     

Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11

In a large collaborative screening project, 370 men with idiopathic azoospermia or severe oligozoospermia were analysed for deletions of 76 DNA loci in Yq11. In 12 individuals, we observed de novo microdeletions involving several DNA loci, while an additional patient had an inherited deletion. They were mapped to three different subregions in Yq11. One subregion coincides to the AZF region defined recently in distal Yq11. The second and third subregion were mapped proximal to it, in proximal and middle Yq11, respectively. The different deletions observed were not overlapping but the extension of the deleted Y DNA in each subregion was similar in each patient analysed. In testis tissue sections, disruption of spermatogenesis was shown to be at the same phase when the microdeletion occurred in the same Yq11 subregion but at a different phase when the microdeletion occurred in a different Yq11 subregion. Therefore, we propose the presence of not one but three spermatogenesis loci in Yq11 and that each locus is active during a different phase of male germ cell development. As the most severe phenotype after deletion of each locus is azoospermia, we designated them as: AZFa, AZFb and AZFc. Their probable phase of function in human spermatogenesis and candidate genes involved will be discussed.      

Photic driving in migraine: correlations with clinical features

Fifty-eight migraineurs were. studied by intermediate frequency steady-state visual evoked potentials (SSVEPs) during headache-free periods. Sex, age, age of onset of migraine, duration of illness, type of migraine, side of pain, sleep .wake disorders, and frequency of migraine attacks did not correlate with any SSVEP abnormalities. On the other hand, visual responsiveness was significantly increased in subjects with family history of migraine, and in those with autonomic symptoms. Our results may indicate that a genetic predisposition to migraine underlies the observed abnormal visual response in migraineurs.     

Nonpalpable breast lesions: recommendations for biopsy based on suspicion of carcinoma at mammography

Carcinoma was found in 30% (119 of 400) of biopsy specimens obtained for mammographically suspicious but nonpalpable findings. The authors reviewed the mammograms of these 400 cases without knowledge of the biopsy results and placed each examination into one of four groups based on their suspicion for carcinoma: minimal (n = 82), slight (n = 91), moderate (n = 174), and high (n = 53). In 127 cases, mammograms showed either minimally suspicious calcifications (n = 33) or minimally (n = 49) or slightly (n = 45) suspicious masses. A 4.7% (six of 127) rate of carcinoma was found in these groups; five of the six cancers were in situ. Had follow-up mammography been done rather than biopsy for these 127 less suspicious lesions, it is probable that the delay in diagnosis would not have altered overall prognosis. In the remaining 273 patients, the positive predictive value of mammography for carcinoma would have risen from 30% (119 of 400) to 41% (113 of 273). The authors conclude that in the management of suspicious nonpalpable mammographic findings, the rate of carcinoma for lesions at biopsy can approximate 40%. This is almost double the rate of most published series.     

5种解热镇痛药的胶束电动毛细管色谱分离研究

报告了5种解热镇痛药——安替比林、4-氨基安替比林、安基比林、安乃近和保泰松的胶束电动毛细管色谱分离、紫外吸收检测法。研究了pH值、有机改性剂(甲醇)和十二烷基硫酸钠(SDS)浓度对分离的影响。在40mmol·L^-1SDS—25mmol·L^-1硼砂—15%甲醇(pH10.5)电泳介质中电泳,上述5组分可达基线分离。迁移时间批内和批间的RSD值分别小于1.3%和2.1%(n=5)。分离的理论塔板数在1.83×10⁴～4.15×10⁴之间。