多脏器微栓塞病细胞综合征动物实验模型──定义、判断标准、发生机制及其与临床的关系

利用健康杂交犬制作了多脏器微栓塞病细胞综合征（ＰＯＭＳ）模型,观察在不同时限、不同组织器官造成的病理生理改变。从中发现,钳夹腹主动脉阻断血流后,其供血器官都发生了ＲＯＭＳ,且不同器官的功能与结构损害有发生时间和程度的不同,但均有不同程度的微栓塞形成趋势,这有助对“多脏器衰竭”概念认识的深化。     

Figures of merit to compare distributed linear inverse solutions

Summary This paper introduces the concept of the resolution matrix as the basis for an objective theoretical comparison of distributed linear inverse solutions to the neuroelectromagnetic inverse problem. In particular, we describe how figures of merit derived from the resolution matrices can be represented graphically to evaluate merits and shortcomings of the different solutions. The use of the figures of merit is illustrated with two solutions that consider minimal a priori information about the generators: Classical Minimum Norm and Backus Gilbert. We recommend to start any analysis with the individual exploration of the resolution kernel for each grid point or at least for those points where the activity is likely to occur. This analysis might help in selecting the optimal inverse for the sources that are supposed to be active in the process under study.This work was supported by a grant from the Deutsche Forschungsgemeinschaft (Klinische Forschergruppe Biomagnetismus and Biosignalanalyse). Partial support was received from Swiss National Foundation grant 4038-044081/1.     

Interleukin-1α (IL-1α) and N-formyl-methionyl-leucyl-phenylalanine (FMLP) as potential inducers of supravital chemotaxis

The phenomenon of artificially induced local leucocyte reactions during the supravital period could be of practical importance, but has not yet been comprehensively investigated. For a more detailed evaluation, experiments with the chemotactic agents interleukin-1 (IL-1) and N-formyl-methionyl-leucyl-phenylalanine (FMLP) were performed by subcutaneous injection into various anatomical regions (back, abdomen, limbs) of NMRI-mice (National Medical Research Institute) and pigs 0–5 min after circulatory arrest. Phosphate buffered saline (PBS) without effective components was administered to equivalent areas of the animals as a control. Tissue specimens were collected at 6 h postmortem (mice) and 12–14 h postmortem (pigs), cut into serial sections, stained with H & E and examined under the microscope. A leucocyte reaction did not develop in pigs (n = 10, 30 tissue samples) following injection of FMLP, however, dermal, subcutaneous and perivascular infiltration of leucocytes (in particular mononuclear cells and a few granulocytes) was found in 3 out of 30 tissue specimens in murine experiments. In addition intravascular cell accumulations were detected in 2 out of 30 samples. The injection of IL-l to mice gave similar results, i.e. aggregations of leucocytes and intravascular cell accumulations in 4 out of 30 and 3 out of 30 tissue samples, respectively. In negative controls no leucocyte reaction was detectable. This shows that potent chemotactic factors such as IL-1 and FMLP administered in the early supravital period can induce moderate local leucocyte reactions in animal models in at least some cases. A clear morphological differentiation between vital and supravital chemotaxis does not seem to be possible. The supravitally stimulated accumulations of leucocytes are interpreted as an aggregation of resident macrophages in combination with a slight migration of blood leucocytes. Presumably, these alterations are restricted to the very early supravital period as long as sufficient energy reserves are available. It must be stated that the observed changes are reactions, not spontaneous actions, so that the general validity of the phenomenon of leucocyte infiltration as a vital parameter is not affected.     

Hybrid Pharmacokinetic Models to Describe Anti-HIV Nucleoside Brain Disposition Following Parent and Prodrug Administration in Mice

Brain delivery of active anti-HIV compounds is important for successful treatment of the AIDS patient. As an initial step in predicting human brain drug concentrations, hybrid pharmacokinetic models were developed to characterize the disposition of anti-HIV nucleosides following parent and prodrug administrations in mice. Mouse data were obtained following intravenous administration of 3-azido-2,3-dideoxyuridine (AZddU or AZDU), 3-azido-3-deoxythymidine (AZT), and their dihydropyridine prodrugs (AZddU-DHP and AZT-DHP). Exponential equations were fitted to the serum concentration–time data for each species, including the pyridinium ion moieties, and subsequently used in differential mass balance equations describing the brain dynamics of each compound. Model parameters for the mass balance equations were estimated by various techniques, including the utilization of in vitro data. In general, model-predicted brain concentrations agreed with the observed data. Similar data in larger animals will permit scale-up of the current model to predict human brain drug concentrations.     

Kinematic models and human elbow flexion movements: Quantitative analysis

Summary The smoothness with which movements are customarily performed has led Hogan (1984) to formulate a model for trajectory planning by the central nervous system in which the goal is to maximize smoothness, one measure of which is the integrated mean squared magnitude of jerk (jerk cost). We tested the applicability of this minimum-jerk model to one-joint goal directed movements performed by human subjects at different speeds and amplitudes, by comparing kinematic parameters and the jerk cost predicted by the mathematical model with values calculated from experimental data. We also tested a higher order, minimum-snap kinematic model. Normal subjects performed elbow flexions of 5 to 50 degrees as rapidly and accurately as possible and also at slower speeds. The boundary conditions of both models were adjusted to account for the failure of subjects to produce movements which reached equilibrium precisely at the target (so that acceleration and velocity reached zero together). Typically, fast movements (< 300 ms duration) were fairly symmetric in that the durations and amplitudes of acceleration and deceleration were approximately equal; slower movements (> 300ms) were asymmetric with strong, brief acceleration peaks and broad, slow deceleration peaks. In fast movements, the calculated jerk cost was consistently higher than predicted by the minimum-jerk model; a good fit to all kinematic parameters was provided by the minimum-snap model (a seventh-order polynomial). Neither model consistently predicted the trajectories of slower movements. We conclude that muscle/limb dynamics can account for the success of the minimum-snap model with fast movements, and that there is no evidence of planning for maximal smoothness in slower movements.     

Headache and family history

In two headache questionnaire surveys we inquired about the occurrence of headache in the mothers, fathers, siblings and children of the respondents. In total, 633 people completed valid questionnaires, 260 in the first survey and 373 in the second. The hypothesis was that familial headache occurrence would be positively associated with headache frequency. In each survey, the regression of headache frequency on the number of parents having headache was highly significant. Neither sex nor the sibling and children variables were significant predictors. In the cross-tabulations of the parental occurrence of headache with headache frequency we saw a clear "break-point" between the "no headache" and the headache frequency categories studied. For the final analyses the dichotomy "headache/no headache" was related in fourfold tables to headache occurrence in the father and the mother separately, and to the number of headache parents. The positive associations were not simply due to the large number of migraine cases since they remained after removing the migraineurs.     

A highly predictable animal model of retinoblastoma

Summary A new animal model of retinoblastoma was developed in newborn inbred CDF rats by intravitreous inoculation of retinal tumor cells (5×10⁴/5 l) derived from the cultured tumor cell line EXP-5. The retinal tumor from which the cell line originated was induced by a single intravitreous inoculation of human adenovirus serotype 12 (5 l of 10⁸ TCID 50/0.1 ml) in syngeneic rats. Within 1 month after intravitreous moculation of EXP-5 cells, a clinically recognizable ocular tumor was obtained in all 39 rats. Ad 12-specific T-antigens were demonstrated in the cultured tumor cells using immunofluorescent techniques. Morphologically these tumor cells closely resembled retinoblastuma, with poorly differentiated intracytoplasmic organelles, solitary cilia with a 9+0 tubule pattern, and abnormal nuclear membrane associated with a set of basal bodies. The significance of this highly manipulable retinal tumor cell line is the capability of providing a full-fledged intravitreous tumor in 1-month-old CDF rats, whose actual life span is known to be 42 months. Transplantable retinal tumors described to date are reviewed breifly and compared with the presently reported cell line.Supported by USPHS grants EY-CA01667, R01-EY-03171, and P30 EY-01784, by grants from the Retina Research Foundation, Houston, Texas, and by the Massachusetts Lions Eye Research Fund Inc.     

Organ-specific acellular matrix for reconstruction of the urinary tract

In urology, replacement of organs or organ segments has proved problematic. Current techniques do not replicate complete organ function, and they cause well-known complications. With the acellular organ-specific matrix we have found a way to regenerate tissue components seen in the normal lower urinary tract. The time required for regeneration depends on the matrix size and function. The matrix is covered by urothelium migrating from the host, after which neovascularization occurs, followed by formation of smooth-muscle cells and nerves. In our studies, normal muscle lining and nerves providing functional tissue were demonstrable and no sign of antigenicity was evident, even after heterologous grafting. The regenerated rat bladder was evaluated by organ bath as well as by in vivo functional tests and demonstrated properties and functions similar to those of host tissue. Besides our obtaining encouraging results in the rat bladder, we also studied the organ-specific acellular matrix in other species (dog and rabbit) and other organ segments (ureter and urethra).     

实验性偏头痛动物模型c-fos、c-jun基因表达

目的　复制实验性偏头痛动物模型并探讨其c -fos、c -jun基因表达。方法　采用CristinaTassorelli硝酸甘油法复制大鼠实验性偏头痛模型。免疫组化ABC法研究偏头痛大鼠脑组织即刻早期基因c -fos、c -jun的表达。结果　硝酸甘油型实验性偏头痛大鼠出现双耳发红、甩头、前肢频繁搔头 ,活动增加等外在表现 ,脑组织c -fos、c -jun基因表达阳性细胞数增加 ,基因表达阳性细胞的面积扩大、灰度降低或变化不大。结论　硝酸甘油型实验偏头痛大鼠模型复制方法简单、重复性较好、脑组织c -fos和c -jun基因异常表达明显 ,可以作为偏头痛治疗药物筛选、药效评价和发病机理研究的动物模型。     

实验性脑脓肿影像学改变的病理基础研究

目的：明确不同时期动物脑脓肿的影像学特征及其相应的病理学改变。方法：制备脑脓肿狗动物模型１４只，采用ＣＴ、ＭＲＩ检查结合多项病理学观测进行动态分析。结果：脑炎期ＭＲＩ对炎症坏死区及水肿范围的显示较ＣＴ扫描更为清晰准确。包膜形成期：ＣＴ上脑脓肿包膜强化是炎症区血脑屏障破坏和新生血管形成所致；ＭＲＩＴ２加权成像上包膜的低信号“暗带”与包膜上的巨噬细胞堆积有关，延迟扫描和ＭＲＩ均能有效地区分脑脓肿的急性脑炎期和包膜形成期，但ＭＲＩ更加准确、迅速。结论：脑脓肿的ＭＲＩ特征与其临床分期及病理学变化的相关性较好，能更加准确、简便、迅速地区别脓肿的脑炎期和包膜形成期，可作为临床诊治脑脓肿的有力参考。