心脏螺旋波演化与驱动的计算机实验

我们利用FitzHugh-Nagumo(FHN)类型方程,对二维心肌可激媒质系统螺旋波(Spiral wave,SW)的形成、演化和控制进行了数值模拟,主要有以下研究结果:(1)改变系统的可激性,不会影响SW的激发区宽度,却改变SW的自转周期和旋波核的大小;当可激性达到某一极限值时,SW的自转周期与旋波核的半径趋于无穷大,系统不再出现SW。(2)对SW的均匀近共振小电流驱动,可以引导旋波头(Spiral wave tip,SWT)的漂移运动;当驱动频率接近SW的自转频率时,SWT会沿着圆周漂移,当驱动频率达到共振频率时,SWT会沿着直线漂移。     

摘除松果体对大鼠学习记忆及基底前脑胆碱能系统的影响

目的　探讨松果体功能减退对大鼠学习记忆及基底前脑胆碱能系统的影响。方法　选用 3月龄SD大鼠 2 4只 ,随机分为对照组、去松果体组和褪黑素 (MT)组。手术摘除松果体。饲养 1个月后用Morris水迷宫测试学习记忆功能 ,同时用组织化学和免疫组化方法测定海马、前额叶皮质AchE纤维和内侧隔核、斜角带核的ChAT神经元的数量。结果　与对照组比较 ,去松果体组逃避潜伏期明显增加 ,海马、前额叶皮质AchE纤维数量明显减少 ,但内侧隔核、斜角带核的ChAT神经元数量变化不明显。结论　大鼠去松果体可引起大鼠学习记忆能力减弱 ,这可能与基底前脑胆碱能神经元的功能下降有关     

C基因型乙型肝炎病毒前C区及基本核心启动子突变与疾病进展的相关性研究

目的探讨HBV前C区（PreC）及基本核心启动子（BCP）突变与慢性乙型肝炎病毒（HBV）感染者疾病进展的关系。方法收集88例慢性HBV感染者血清标本，包括36例无症状携带者（其中24例为HBV携带者，12例为HBsAg携带者）、36例慢性乙型肝炎（慢性乙肝）和16例肝硬化患者。所有标本均经型特异性引物PCR法鉴定为HBVC基因型，并用巢氏PCR法扩增HBVPreC和BCP基因片段，用PCR产物直接测序法测序，然后用ClustalW1．8软件进行序列分析。结果在50例HBeAg阳性患者中，无症状携带者、慢性乙肝和肝硬化组的T1762／A1764双突变率和T1846突变率分别为12．5％、42．1％、100％和0％、5．3％、28．6％，差异均有统计学意义（P值分别为0．03和0．02）。在38例HBeAg阴性HBV感染者中，无症状携带者、慢性乙肝和肝硬化组的T1762／A1764双突变率分别为16．7％、58．8％和66．7％，差异无统计学意义（P=0．08）。肝硬化组的C／G1753突变率显著高于无症状携带者及慢性乙肝组（分别为55．6％、8．3％、11．8％，P=0．01），其A1896突变率也高于无症状携带者组（分别为55．6％、8．3％，P=0．01）。结论HBVT1762／A1764双突变与C基因型HBV慢性感染者的疾病进展有关。     

A tumour necrosis factor-alpha (TNF-α) promoter polymorphism is associated with chronic hepatitis B infection

Cytokines such as TNF-α and interferon gamma (IFN-γ) are important for the elimination of infected hepatocytes during acute hepatitis B virus (HBV) infection. Two G versus A transitions in the TNF-α promoter region at positions ?308 and ?238 possibly influence TNF-α expression. We investigated these TNF-α polymorphisms in 71 patients with chronic HBV infection, in 32 subjects that had spontaneously recovered from acute HBV infection, and in 99 healthy controls. The ?238 A promoter variant was present in 18 (25%) of 71 patients with chronic HBV infection compared with two (6%) of 32 subjects with acute infection (P < 0.04), and seven (7%) of 99 controls (P < 0.003). By contrast, the prevalence of the variant at position ?308 was similar in all investigated groups. The observed differences could not be explained by linkage disequilibrium to HLA-B or -DRB1* alleles. These findings suggest an association between the TNF-α promoter polymorphism at position ?238 and the development of chronic HBV infection. This promoter variant appears to be linked to defective viral clearance.     

An enzyme-linked immunosorbent assay (ELISA) for the measurement of antibodies to different parts of the gram-negative lipopolysaccharide core region

Bovine serum albumin was complexed with the core antigens of either Escherichia coli J5 LPS, Salmonella minnesota R595 LPS or E. coli lipid A. These core-BSA complexes were used for solid-phase coating in ELISAs for anti-core antibodies. Antibodies, binding to various parts of the core region were easily quantified in a single experimental set-up, which was hitherto not possible. The ELISA has only 3 incubation steps and is not costly as only moderate amounts of the core antigens (i.e., 1 microgram per test) were needed for coating. The sensitivity proved to be excellent and the complexes were biologically fully active (compared to native, smooth LPS), which make them suitable for the screening (after fusion) of monoclonal anti-core antibodies. Another possible application is the large-scale screening of blood-bank sera in order to find samples with a high anti-core antibody content.     

Matrix metalloproteinase expression in basal cell carcinoma: relationship between enzyme profile and collagen fragmentation pattern

Matrix metalloproteinases (MMPs) with collagenolytic and gelatinolytic activities are up-regulated in basal cell carcinoma. In the present study we demonstrate that the major collagenolytic enzyme detected is MMP-1 (interstitial collagenase) while gelatinolytic enzymes include both MMP-2 (72-kDa gelatinase A) and MMP-9 (92-kDa gelatinase B). Significant fractions of all three enzymes are present as active forms. In spite of the fact that high levels of gelatinolytic enzymes are present, the major fragmentation products resulting from digestion of intact type I collagen are the 1/4 and 3/4 fragments (products of MMP-1-mediated digestion). Thus, it appears that the gelatinolytic enzymes are not capable of degrading the collagen fragments as rapidly as they are produced. Since previous studies have demonstrated that interaction of interstitial fibroblasts with high molecular weight fragments of type I collagen leads to increased MMP production, the present results suggest a mechanism underlying altered function of stromal elements in the connective tissue adjacent to the growing neoplasm.     

Significance of beta-catenin and pRB pathway components in malignant ovarian germ cell tumours: INK4A promoter CpG island methylation is associated with cell proliferation

To clarify the mechanisms underlying cell cycle promotion in malignant germ cell tumours of the ovary (MGCTOs), beta-catenin and components of the pRB pathway, cyclin D1 and p16, were analysed in relation to cell proliferation. Immunohistochemically, p16 protein was not expressed in a number of MGCTOs (9 of 42 tumours: 21.4%) and was associated with p16 gene (INK4A) promoter 5'-CpG islands methylation. Amplification of the cyclin D1 gene (CCND1) was detected in a small number of MGCTOs (5 of 42 tumours: 13.5%). Reduced expression of p16 due to promoter methylation correlated significantly with increased cell proliferation as evidenced by Ki-67 labelling index (p < 0.001) and mitotic index (p < 0.01). In some tumour types, nuclear localization of beta-catenin has been reported to be associated with beta-catenin gene (CTNNB1) mutation, cyclin D1 overexpression, and increased cell proliferation. Nuclear localization of beta-catenin, which was observed in MGCTOs other than dysgerminoma, was not associated with cyclin D1 expression and increased cell proliferation, but appeared to be related to tumour differentiation. Furthermore, CTNNB1 mutations were not detected in any of the MGCTOs examined. Our results suggest that reduced expression of p16 due to INK4A promoter methylation is one of the principal factors that promote cell proliferation in MGCTOs. Thus, p16 may be a novel target for gene therapies to treat MGCTOs.     

Bicuculline-induced circling from the rat superior colliculus is blocked by GABA microinjection into the deep cerebellar nuclei

In a recent electrophysiological experiment, we showed the deep cerebellar nuclei to be a major source of excitatory input to the superior colliculus. Furthermore, target neurons in the colliculus were found, in every case, to receive convergent tonic inhibitory input from the substantia nigra pars reticulata. In the present study, we investigated these effects in the awake rat. We asked whether circling behaviour, induced by unilateral injection of a GABA antagonist into the lateral colliculus, could be suppressed by concurrent cerebellar inactivation. Rats were chronically implanted with bilateral guide cannulae located above the superior colliculus and deep cerebellar nuclei. Bicuculline methiodide (25 pmol) was microinjected unilaterally into intermediate layers of the colliculus at increasing depths until an optimal contralateral circling response was elicited. This behaviour was taken as the baseline response and was the first of three treatments. The second was an identical manipulation of the colliculus with a concurrent 200-nl microinjection of 1 M GABA into the contralateral deep cerebellar nuclei. The third was a repeat of BIC alone into the colliculus or, if rotation had been suppressed by more than 50% on test 2, the treatment was collicular BIC plus deep cerebellar saline. This latter treatment was used as a control for possible non-pharmacological injection effects. The effect of cerebellar GABA at 26 sites (17 within cerebellar nuclei and 9 outside) on BIC-induced rotation at 15 collicular sites was studied in ten animals. Only GABA injections at sites that fell within the cerebellar nuclei significantly reduced turning (P<0.0001). A full behavioural analysis showed that this was a specific suppression of turning, not the result of general motor impairment. These results provide clear behavioural evidence that opposing, convergent influences from the basal ganglia and cerebellum interact in the lateral superior colliculus to control head and body movements. They furthermore suggest that the tonic deep cerebellar excitation of the superior colliculus could be the driving force in the expression of rotation induced by manipulations of the basal ganglia.     

Evidence that non-NMDA receptors are involved in the excitatory pathway from the pedunculopontine region to nigrostriatal dopaminergic neurons

Summary Extracellular single-neuron recordings were obtained from electrophysiologically identified nigrostriatal neurons in chloral hydrate anesthetized rats, in order to test the hypothesis that excitatory amino acid receptors are involved in responses of these neurons to electrical stimulation of the pontine region where the pedunculopontine nucleus (PPN) is located. The effects of iontophoretic application of excitatory amino acids and their antagonists as well as of cholinergic antagonists were tested on the fast orthodromic excitation of nigrostriatal neurons evoked by stimulation of the PPN region. The N-methyl-D-aspartate (NMDA) receptor antagonist D-a-aminoadipic acid as well as the cholinergic receptor antagonists mecamylamine and atropine failed to suppress the synaptic excitation of nigral neurons. The NMDA receptor antagonist DL-2-amino-5-phosphonovalerate exerted a weak depressant action on the synaptic response in a few neurons only. On the contrary, the broad spectrum antagonists of excitatory amino acid receptors kynurenic acid and gamma-Dglutamyl-amino-methyl-sulphonate were found to block simultaneously both the synaptic excitation and the neuronal responses to iontophoretic pulses of glutamate while leaving unaffected the neuronal responses to local application of acetylcholine or carbachol. The competitive antagonist of non-NMDA receptors 6-cyano-2,3-dihy-droxy-7-nitro-quinoxaline suppressed the synaptic excitation at ejection currents which antagonized neuronal responses to quisqualate and kainate. These results suggest that PPN excitatory fibers synapsing onto pars compacta nigrostriatal neurons utilize an excitatory amino acid as a synaptic transmitter acting preferentially on non-NMDA receptors.