磷脂酶C-γ1在人胚胎脊髓中的表达变化

为了了解磷脂酶C-γ1(PLC-γ1)的发育表达变化特点,本研究采用免疫组织化学方法检测不同发育时期的人胚胎脊髓中PLC-γ1的表达及变化。结果显示:PLC-γ1在人胚胎脊髓3周到7个月的整个发育过程中均有表达,在发育早期阳性反应可见于神经管内、外界膜,随着套层、边缘层的形成,神经上皮层、套层中均可见到PLC-γ1阳性反应物,且翼板阳性细胞较基板密集;套层阳性细胞在8、9周时达到高峰,随后开始逐渐减少。3个月时边缘层出现散在的阳性细胞,并随着脊髓的发育而逐渐增多。以上结果提示,PLC-γ1及其与PLC-γ1相关的细胞信号通路对人胚胎脊髓的发育可能发挥了重要的生物学作用。     

Benzodiazepines both enhance gamma-aminobutyrate responses and decrease calcium action potentials in guinea-pig myenteric neurones

The effect of two benzodiazepines, midazolam and diazepam, was studied in guinea-pig myenteric neurones, using intracellular recording techniques. Both these benzodiazepines (100-300 pM) potentiated the rapidly desensitizing, bicuculline-sensitive depolarization, induced by alpha-aminobutyrate ionophoresis. Concentrations of midazolam and diazepam higher than 100 nM depressed the gamma-aminobutyrate-induced depolarization. The potentiating effect of the benzodiazepines was reversibly abolished by Ro 15-1788 (1-100 nM) and by pentylenetetrazol (100 microM). A second effect of midazolam and diazepam (100-300 pM) was a reversible depression of the amplitude and duration of the directly evoked action potential in 29% of neurones, without affecting membrane potential or conductance. The effect was very marked when electrodes were filled with CsCl, and was also seen in the presence of tetrodotoxin. In some but not all of these neurones, the amplitude and duration of the action potentials was reduced also by gamma-aminobutyrate (1-10 microM). Ro 15-1788 and pentylenetetrazol reversibly abolished the effect of benzodiazepines on the action potential, but not that of gamma-aminobutyrate. Thus, benzodiazepines have two effects on myenteric neurones. The first is an enhancement of the gamma-aminobutyrate response (activation of Cl conductance); the second is a depression of the calcium action potential, which appears to be independent of gamma-aminobutyrate.     

The nucleus basalis magnocellularis: The origin of a cholinergic projection to the neocortex of the rat

The cells of origin of a neocortical cholinergic afferent projection have been identified by anterograde and retrograde methods in the rat. Horseradish peroxidase injected into neocortex labelled large, acetylcholinesterase-rich neurons in the ventromedial extremity of the globus pallidus. This same group of neurons underwent retrograde degeneration following cortical ablations. The region in which cell depletion occurred also showed significant decreases in the activities of choline acetyltransferase and acetylcholinesterase. Discrete electrolytic and kainic acid lesions restricted to the medial part of the globus pallidus each resulted in significant depletions of neocortical choline acetyltransferase and acetylcholinesterase. Hemitransections caudal to this cell group did not result in such depletions. Taken together these observations suggest that the acetylcholinesterase-rich neurons lying in the ventromedial extremity of the globus pallidus, as mapped in this study, constitute the origin of a major subcortical cholinergic projection to the neocortex. The utility of acetylcholinesterase histochemistry in animals pretreated with di-isopropylphosphorofluoridate in identifying cholinergic neurons is discussed in the light of this example; specifically, it is proposed that high acetylcholinesterase activity 4–8 h after this pretreatment is a necessary, but not sufficient, criterion for the identification of cholinergic perikarya.The neurons in question appear to be homologous to the nucleus basalis of the substantia innominata of primates, and are thus termed ‘nucleus basalis magnocellularis’ in the rat. No evidence was obtained to support the hypothesis that nucleus of the diagonal band projects to neocortex. However, striking similarities in size and acetylcholinesterase activity were observed among the putative cholinergic perikarya of the nucleus basalis magnocellularis, the nucleus of the diagonal band, and the medial septal nucleus.Kainic acid lesions of the neocortex produced uniform and complete destruction of neuronal perikarya. These lesions decreased neocortical glutamic acid decar?ylase activity, suggesting that there are GABAergic perikarya in the neocortex. However, the same lesions did not affect neocortical choline acetyltransferase. This observation suggests that there are no cholinergic perikarya in the neocortex, a conclusion that is consistent with the absence of intensely acetylcholinesterase-reactive neurons in the neocortex.     

Synaptic efficacy of inhibitory synapses in hypoglossal motoneurons after transection of the hypoglossal nerves

In cat hypoglossal motoneurons after axotomy the synaptic efficacy of inhibitory synapses made by the lingual nerve afferent fibers was studied. The amplitude of the short- and the long-lasting inhibitory postsynaptic potential produced in tongue protruder motoneurons 24 days after axotomy by stimulation of the lingual nerve was significantly reduced in size as compared with the control on the unoperated side. In most protruder motoneurons 40 days after axotomy a large excitatory postsynaptic potential and a spike was produced by stimulation of either the ipsilateral or the contralateral lingual nerve. We have demonstrated that the decline of synaptic efficacy of inhibitory synapses for the short-lasting inhibitory postsynaptic potential was more prominent than that for the long-lasting inhibitory potential in the motoneuron 24 days after axotomy. After the cut axons of protruder motoneurons were re-united to tongue muscles, we have demonstrated that the decline of synaptic efficacy of inhibitory synapses for the short-lasting inhibitory postsynaptic potential was less prominent than that in axotomized protruder motoneurons.     

鸡干扰素-γ抗球虫作用研究进展

干扰素-γ（IFN-γ）是一种重要的细胞因子,主要由T细胞、NK细胞产生,具有广谱抗病毒、抗肿瘤和双向免疫调节作用。重组鸡干扰素-γ（rChIFN-γ）已被证明与鸡球虫病的免疫有关。本文就鸡干扰素-γ（ChIFN-γ）的生物学特性及其抗球虫作用的研究进展作一综述。     

Differential cytokine profile in children with cystic fibrosis

The previously observed occurrence of antineutrophil cytoplasmic autoantibodies (ANCA) in patients who have cystic fibrosis (CF), together with the reported decrease in IgG2, a Th1-controlled isotype, suggests a potential for Th1/Th2 imbalance in CF patients with a possible Th2 predominance. 48 CF patients and 16 controls had levels of IFNgamma, IL-4, and IL-10 measured in supernatants of whole blood cell cultures stimulated by lipopolysaccharide (LPS) and phytohemaglutinine (PHA). The patients were divided into 2 groups: "low responders", having negligible secretion of cytokines (IFNgamma: 10.0-200.0 pg/ml, IL-4: 0.0-0.3 pg/ml) and "high responders", producing high levels of both IFNgamma (500.0-2000.0 pg/ml) and IL-4 (1.0-200.0 pg/ml). There was a statistically significant (P < 0.01) deterioration of lung function measured by an FEV(1) decline by 11.2% over 3 years in the "low responder" group. 10 of 16 "low responders" had chronic lung infections with P. aeruginosa while such infection was less prevalent in the "high responder" group where only 13 of 32 CF patients had positive cultures. A shift towards Th2 response was observed in the "high responder" group as children chronically infected with P. aeruginosa had greater IL-4 production than non-infected CF patients within the same cohort. ANCA autoantibodies were found only in the "high responder" group. Th2 immune response predominance in a subset of CF patients is associated with chronic P. aeruginosa infection.     

Evoked field potential analysis of dopaminergic mechanisms in the isolated turtle olfactory bulb

Dopaminergic mechanisms were Anatyzed in an isolated preparation of the turtle olfactory bulb. Field potentials were evoked by antidromic or orthodromic stimulation, and the effects determined of pharmacological manipulations of the bathing medium. In the presence of dopamine or a dopamine agonist, apomorphine, there was a reduction of amplitude and delay of onset of the component of the field potentials due to granule cell responses; fluphenazine, a dopamine antagonist, had generally opposite effects. Using paired volleys, it was found that the suppression of the response to the second test volley was reduced in the presence of dopamine or apomorphine, but enhanced in the presence of fluphenazine.The most likely explanation of these results is that exogenous dopamine depresses the response of mitral cells, which in turn decreases the dendrodendritic synaptic excitation of granule cells and reduces their inhibitory feedback onto mitral cells. This suggests that the dopaminergic cells in the bulb may suppress mitral cells by modulating excitable mechanisms in the mitral dendritic membrane, or modulating long-lasting synaptic potentials.     

gamma-Aminobutyric acid and taurine release in the striatum of the rat during hypoglycemic coma, studied by microdialysis

Extracellular levels of striatal gamma-aminobutyric acid (GABA) and taurine were monitored during insulin-induced hypoglycemia using microdialysis. At the onset of isoelectricity in the electroencephalogram (EEG), a transient 5-fold increase in the levels of GABA occurred. Taurine levels increased 5 min following the onset of isoelectricity and continued to increase during the entire isoelectric period. The results demonstrate that events associated with the onset of isoelectricity during hypoglycemia trigger an increase in extracellular concentrations of GABA and taurine. The discrepancy in time-course of these changes may reflect differences in compartmentation, function and metabolism of the two amino acids.     

The regional distribution and cellular localization of iron in the rat brain

The regional distribution and cellular localization of iron throughout the rat brain was determined with iron histochemistry. Densitometry was used to measure the intensity of stain of 51 iron-concentrating sites. Among the areas of highest iron content are the circumventricular organs, islands of Calleja, globus pallidus, ventral pallidum, substantia nigra pars reticulata, interpeduncular nucleus, dentate nucleus, and interpositus nucleus. Iron occurs most commonly in oligodendrocytes and in the fibrous network of the neuropil, but is also found in the interstitial spaces of circumventricular organs and in the tanycytes of the organum vasculosum of the lamina terminalis, median eminence, and walls of the third ventricle. In diverse areas throughout the brain—among them, the islands of Calleja, dentate gyrus of the hippocampal formation, lateral septal nucleus, and central amygdala—iron is found in association with the perikarya and neuronal processes of nerve cells.The overlapping distribution patterns of iron and γ-aminobutyric acid, enkephalin, and luteinizing hormone-releasing hormone suggest that the distribution of iron is related to its association with the metabolism of one or more neurotransmitters or neuroactive compounds.     

Morphologic evaluation of the liver in hereditary angioedema patients on long-term treatment with androgen derivatives

17 alpha-Alkylated androgens are highly effective in preventing attacks in HAE patients. These drugs, however, seem to be implicated in the development of cholestatic jaundice, peliosis hepatis, and liver tumors. In order to assess the risk-benefit balance of the long-term therapy with androgen derivatives, a follow-up investigation was performed in 13 HAE patients. The results of this study indicate that long-term treatment (15 to 47 mo) with low doses of danazol or stanozolol does not induce significant hepatic damage detectable by laboratory tests or liver biopsy. However, the limited number of patients, although in a rather long period of observation, still suggests a careful control and the use of minimal effective doses.