Magnetic resonance imaging of antibody-mediated demyelinating experimental allergic encephalomyelitis

Two models of demyelinating experimental allergic encephalomyelitis (EAE) were studied on Lewis rats in whom the disease was induced by injections of either (i) lentil-lectine binding myelin glycoproteins plus myelin basic protein (MBP)-specific T cells (36 rats), or (ii) myelin/oligodendrocyte glycoprotein-specific monoclonal antibody plus MBP-specific T cells (16 rats). In our 24 control rats, 20 received MBP-specific T cells only, and four received myelin glycoproteins plus purified protein derivative-specific T cells. The extent of the resulting blood-brain barrier (BBB) permeability, vasogenic oedema and/or demyelination was assessed in vivo using magnetic resonance imaging (MRI) techniques. The results show that in both demyelinating EAE models the disease appeared more quickly, progressed very rapidly and was more severe than when induced with a similar number of MBP-specific T cells alone. Almost all animals developed hypercute EAE, with a very high mortality rate. MRI showed a very intense BBB breakdown and vasogenic oedema in all the normally ‘leaky’ areas of the central nervous system, and focal lesions corresponding to plaque formation in the brain stem or spinal cord near the ‘leaky’ areas. During the 40-day observation period, the rare survivors of this hyperacute form of EAE presented a chronic form of EAE with serious sequelae. Our results demonstrate that the synergistic effect observed between MBP-specific T cells and antibodies to myelin glycoproteins, especially to myelin/oligodendrocyte glycoprotein, does not only induced demyelinating lesions and chronic clinical signs, but is further responsible, via the normally ‘leaky areas’, for the fatal increase of the BBB breakdown and vasogenic oedema of which there are ample acute clinical signs.     

Rib-vertebral angle asymmetry in idiopathic, neuromuscular and experimentally induced scoliosis

The concave and convex rib-vertebral angle (RVA) at levels T2–T12 was measured on AP radiographs of 19 patients with right convex idiopathic thoracic scoliosis and 10 patients with major thoracic right convex neuromuscular scoliosis. The difference between the angles on the concave and the convex sides, the RVAD, was calculated. The RVAs were also measured on radiographs from three animal groups in which spinal curves had been induced experimentally in a variety of ways. Group 1 comprised 16 rabbits that had been subjected to selective electrostimulation of the latissimus dorsi, the erector spinae and the intercostal muscles. Group 2 comprised four dead rabbits whose spines had been subjected to manual bending. Group 3 comprised eight rabbits that had undergone mechanical elongation of one rib. In both the idiopathic and the neuromuscular group, the convex RVA was smaller than the concave RVA between levels T2 and T8, with a maximal difference between T4 to T5. From T9 to T12 the concave RVA was smaller than the convex. The RVA in relation to the scoliotic segment, i.e. the apex level of the curve and the two neighbouring vertebrae above and below this level, showed similar results. With increasing Cobb angle the RVADs increased linearly with the greatest difference at the second vertebra above the apex. In the three experimental groups the pattern of the RVADs between T6 to T12 was basically similar to the findings of the clinical study. From the results of these clinical and experimental studies, it is concluded that the typical pattern of the RVAs on the concave and convex sides seems to be independent of the underlying cause of the spinal curvature. It is likely that the RVADs result from a passive mechanical adaptation of the ribs to the lateral curvature of the spine.     

槲皮素磷酸酯钾对实验性心肌梗塞的影响

iv10～20mg/kg(木解)皮素磷酸酯钾使兔急性心肌梗塞范围明显缩小,ST段明显降低,并能对抗冠脉结扎后引起的血清CPK含量增加及心律失常,这些作用与普萘洛尔相似。但iv40mg/kg后作用不明显。     

实验动物大白鼠型流行性出血热流行病学和临床症状调查

本文对59名接触实验动物大白鼠引起23例流行性出血热(EHF)的流行病学和临床症状进行了调查,发病率为38.98%。发病的有副教授、讲师、助教、研究生等。发病多在春季,年龄组在21～40岁,男多于女。经间接免疫荧光技术检查,大白鼠肺EHFV抗原阳性率为32.69%。临床分型以中型为多,其次为重型和轻型。临床症状以发热、头痛、腰痛、全身痛、食欲不振、酒醉貌为主,没有死亡病例。血清间接免疫荧光抗体IgG在1:320～1:5 120之间的占91.30%。     

多媒体技术在医学生物学实验教学中的应用

本文联系医学生物学实验课程和多媒体技术的特点，探讨了多媒体技术在医学生物学实验教学中的应用。指出在基础医学实验教学中教师要利用多媒体技术的优点，结合课件制作和教学中应注意的问题，才能充分发挥多媒体技术在教学中的作用，提高教学质量。     

A simple mechanical model using a piston to produce localized cerebral contusions in pigs

Summary A simple mechanical model using a piston to produce localized cerebral contusions in pigs, is presented.The precision and reproducibility of the method are described by the biomechanical and pathological results.There are only pathological changes with haemorrhage and laceration close to the place of entry of the piston. The changes in the physiological parameters also indicate that the damage is focal.In this model, when kept intact, the dura mater offers considerable protection as no pathological changes in the brain are observed even when the energy at the time of the contusion is increased to twice the values which, when the dura is open, cause considerable damage.     

Competitive dissociation of encephalitogenic complexes between antigen presenting cells and myelin basic protein

Splenic T cells from myelin basic protein (MBP)-immunised Lewis rats were activated to transfer experimental autoimmune encephalomyelitis (EAE) by co-culture with MBP-pulsed lymphoid dendritic cells (DC). MBP-pulsed DC could be kept for at least 24 h at 37 degrees C in antigen-free medium without affecting their ability subsequently to activate encephalitogenic T cells. However, MBP-pulsed DC were rendered much less stimulatory after a 6 h, but not 2 h, secondary incubation with ovalbumin. Thus, although encephalitogenic complexes between MBP and DC appear very stable in the absence of competing antigens, in their presence, antigen exchange can take place over a period of a few hours; this has positive implications for therapy of EAE by antigen competition.     

Suppression of experimental allergic encephalomyelitis by the encephalitogenic peptide, in solution or bound to liposomes

We have investigated the ability of liposome-bound encephalitogenic peptide to suppress experimental allergic encephalomyelitis (EAE) in the guinea pig. EAE was induced by challenge with the encephalitogenic peptide, residues 113-122 of human myelin basic protein (MBP) in complete Freund's adjuvant. The peptide was acylated with stearic acid in order to anchor it to the lipid bilayer. The liposomal-bound peptide effectively suppressed clinical signs of EAE at relatively low doses, when given subcutaneously or intraperitoneally without incomplete Freund's adjuvant, several days after challenge. In vitro proliferation of lymphocytes from treated, protected animals in response to the peptide was greatly decreased but that to the purified protein derivative of tuberculin antigen was not, indicating an antigen-specific effect. However, histological signs of EAE were not reduced. The free peptide in solution was somewhat less effective when given intraperitoneally but was as or nearly as effective as liposome-bound peptide when given subcutaneously. Binding to liposomes may decrease the rate of clearance or degradation of the peptide when given intraperitoneally.     

The logical structure and validity of experimental designs in pharmacokinetics and clinical pharmacology

Much of the literature on research design in clinical pharmacology and pharmacokinetics emphasizes statistical concerns, thus suggesting that a primary ingredient of a valid research design is an appropriate plan for statistical analysis of data. However, statistical validity is only one of several ways to evaluate an experimental study. The present paper reviews the underlying logic and sources of invalidity of experimental drug research suggesting influences and factors which may deceive or lure an experimenter into erroneous conclusions.     

Absence of donor-type major histocompatibility complex class I antigen-bearing microglia in the rat central nervous system of radiation bone marrow chimeras

Localization of bone marrow-originated cells in the central nervous system (CNS) of the rat was investigated by using bone marrow chimeras. In order to do this, Lewis rats which carry major histocompatibility complex (MHC) class I antigens haplotype 1 (RT1.Al) were reconstituted with (Lew X PVG)F1 (RT1.Al/c) bone marrow cells after lethal irradiation. Transferred bone marrow cells were detected by immunohistochemical staining using a monoclonal antibody, OX27, specific for haplotype c of rat MHC class I antigens (RT1.Ac). The spleen and thymus of chimeric rats were fully reconstituted with transferred F1 cells 4 weeks after bone marrow transplantation. At this stage, mononuclear cells in the subarachnoid space of the CNS expressed OX27 antigen indicating that they were of bone marrow origin. A few OX27-positive blood cells were scattered in the CNS parenchyma 4-12 weeks after reconstitution. Ramified microglia, however, remained OX27-negative. Bone marrow-derived microglia were not observed throughout the period of examination until 24 weeks. In addition, experimental allergic encephalomyelitis (EAE) was induced in chimeric rats in order to augment the expression of MHC class I antigens on microglia. Even under this condition, no OX27-positive microglia were observed. Taken together, ramified microglia might be of neuroectodermal origin and there is little possibility that the microglia are derived from the bone marrow. However, if the ramified microglia are derived from blood cells, the microglia may be expected to have characteristic cell kinetics from the following points: (1) the precursor cells of the microglia may enter the CNS only at the perinatal stage; and (2) even under the condition in which lymphocytes and macrophages enter the CNS as observed in EAE, the precursor cells of the microglia are not supplied from the blood.