基于蒙特利尔病变部位分型的克罗恩病患者临床特征分析

目的 探讨回肠末段型（L1）、结肠型（L2）及回结肠型（L3）克罗恩病（CD）患者的临床特征、实验室检查、疾病行为等方面的差异。方法 回顾性研究2021年1月—2022年6月武汉大学人民医院181例CD患者的临床资料,其中L1型CD患者66例,L2型CD患者20例,L3型CD患者95例。收集患者临床资料和实验室检查结果等,分析3组患者在临床特征和实验室检查结果等方面的差异。多因素二元Logistic回归分析L1、L2和L3型CD患者临床特征。绘制受试者工作特征（ROC）曲线,分析部分临床特征预测CD病变部位的效能。结果 L1组患者平均年龄大于L3组患者（P <0.05）。L1组患者黏液脓血便构成比低于L2和L3组患者（P <0.05）。L1组患者平均血小板计数低于L3组患者（P <0.05）。L1组患者肛周病变构成比低于L2和L3组患者（P <0.05）。多因素二元Logistic回归分析结果显示,L2型CD［O^R =1.017（95% CI：1.004,1.031）］和L3型CD［O^R =1.026（95% CI：1.016,1.037）］与CD疾病活动指数（CDAI）相关（P <0.05）,L3型CD［O^R =7.088（95% CI：2.390,21.018）］与肛周病变风险增加相关（P <0.05）。ROC曲线分析结果显示,与L1型CD比较,当血沉为29.50 mm/h时,L2型CD的ROC曲线下面积（AUC）为0.724（95% CI：0.579,0.868）,此时预测L2型CD敏感性为77.8%（95% CI：0.519,0.926）,特异性为64.1%（95% CI：0.510,0.754）;当血小板计数取临界值307×10⁹/L时,L3型CD的AUC为0.702（95% CI：0.618,0.785）,此时预测L3型CD敏感性为72.3%（95% CI：0.602,0.826）,特异性为65.2%（95% CI：0.554,0.752）。结论 L1型、L2型及L3型CD患者的临床表现、实验室检查、疾病行为等均存在差异,基于这些特征将有助于鉴别CD患者的不同病变部位。     

Autoradiographic localization of dopamine uptake sites in the rat brain with3H-GBR 12935

Summary The firing rate and terminal excitability of identified nigrostriatal dopamine (DA) neurons was determined before, and over a 10–15 min period following, direct intrastriatal administration of the glutamate (GLU) agonist NMDA, or saline. NMDA (0.025 and 0.075 mol) produced a short latency increase in DA cell firing rate. In 7/8 cases, this increase in firing rate was accompanied by a profound reduction in terminal excitability. The decrease in excitability usually outlasted the increase in firing rate (sometimes by more than 8 min), and was superseded at a later stage by a marked increase in excitability. None of these effects were seen with saline (n=5), and they could all be blocked by preadministration of the competitive NMDA antagonist AP-7 (0.025 mol; n=6). The sequence of events leading to the observed results is argued to be as follows; NMDA initially excites striatal efferents to the DA cell, which through disinhibition and direct stimulation increase DA cell firing rate. Increased firing rate leads to enhanced striatal DA release. Dopamine's inhibitory influence pre-empts any effect NMDA itself may have on the terminals of nigrostriatal neurons, and counteracts NMDA's stimulatory effect on striatal output cells. Furthermore, the marked reduction in terminal excitability suggests that DA becomes the dominant influence in the striatum for a time. Hence, the net outcome of the injection is augmented striatal DA tone. Later, the effect of residual NMDA becomes predominant once more.     

Inhibitory action of Ca2+ on spontaneous transmitter release at motor nerve terminals in a high K+ solution

The inhibitory effect of a high external Ca²⁺ ([Ca²⁺]_o) on spontaneous transmitter release in a high K⁺ solution (Gage and Quastel 1966; Birks et al. 1968) was studied at the frog neuromuscular junction, based on the hypothesis that an increased intracellular free Ca²⁺ ([Ca²⁺]_i) in the nerve terminal plays a key role in the depression. Three procedures were employed to increase [Ca²⁺]_i; increasing [Ca²⁺]_o, application of caffeine and tetanic nerve stimulation. All of these procedures increased m.e.p.p. frequency in normal Ringer. However, as the basic m.e.p.p. frequency was increased by raising the external K⁺ concentration (7–15 mM), their facilitatory effects on m.e.p.p. frequency decreased, disappeared and eventually reversed to depressant actions. Since a rise in the external K⁺ concentration would increase the steady state level of [Ca²⁺]_i, it is suggested that when the [Ca²⁺]_i is preset at a high level, manipulations so as to further increase [Ca²⁺]_i depress spontaneous release of transmitter. Possible mechanisms for this inhibition was discussed in relation to a question whether or not the rate of spontaneous transmitter release is a monotonic function of [Ca²⁺]_i.     

The isolation of pure cholinergic nerve terminal sacs (T-sacs) from the electric organ of juvenile Torpedo.

The problem of synaptosome formation in the electric organ of Torpedo has been re-investigated using tissue from juvenile fish. This tissue is softer than adult material and can be easily homogenized in an Aldridge-type homogenizer. Homogenates so prepared contain a significant number of synaptosome-like structures which can be purified by differential and density gradient centrifugation. The purified particles are enriched in acetylcholine and choline acetyltransferase; they also contain lactate dehydrogenase activity, most of which is in an occluded form. The structure of these particles as revealed by electron microscopy is unusual in that they have no post-synaptic adhesions, relatively few synaptic vesicles and no intraterminal mitochondria. Because of their unusual morphology we have named these particles nerve terminal sacs (T-sacs). A high-affinity, hemicholinium-3 sensitive choline uptake system with an apparent K_m of 1–3 μm is associated with the T-sacs.     

The linear plasmid pSA3239 is essential for the replication of the Streptomyces lavendulae subsp. lavendulae CCM 3239 chromosome

We previously reported the complete genome of Streptomyces lavendulae subsp. lavendulae CCM 3239, containing the linear chromosome and the large linear plasmid pSA3239. Although the chromosome exhibited replication features characteristic for the archetypal end-patching replication, it lacked the tap/tpg gene pair for two proteins essential for this process. However, this archetypal tpgSa-tapSa operon is present in pSA3239. Complete genomic sequence of the S. lavendulae Del-LP strain lacking this plasmid revealed the circularization of its chromosome with a large deletion of both arms. These results suggest an essential role of pSA3239-encoded TapSa/TpgSa in the end-patching replication of the chromosome.     

Human multiple myeloma cells express peroxisome proliferator-activated receptor gamma and undergo apoptosis upon exposure to PPARgamma ligands

Multiple myeloma is essentially an incurable malignancy and it is therefore of great interest to develop new therapeutic approaches. We previously reported that human B cell-lymphomas express the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) and are killed by PPARgamma ligands. Herein, we investigate the therapeutic potential of PPARgamma ligands for multiple myeloma. The human multiple myeloma cell lines ANBL6 and 8226 express PPARgamma mRNA and protein. The PPARgamma ligands, 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) and ciglitazone, induced multiple myeloma cell apoptosis as determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, loss of mitochondrial membrane potential, and caspase activation. Importantly, the ability of PPARgamma ligands to kill both multiple myeloma cell lines was not abrogated by Interleukin-6 (IL-6), a multiple myeloma growth survival factor. Finally, the RXR ligand 9-cis retinoic acid (9-cis RA) in combination with PPARgamma ligands greatly enhanced multiple myeloma cell killing. These new findings support that PPARgamma ligands may represent a novel therapy for multiple myeloma.     

Regulation of GABA release by depolarisation-evoked Ca2+ transients at a single hippocampal terminal

We correlated dynamic changes in free cytosolic [Ca²⁺] ([Ca²⁺]_i) within single presynaptic terminals of cultured hippocampal neurones with the postsynaptic GABA-mediated currents. The local changes in [Ca²⁺]_i and evoked inhibitory postsynaptic currents (eIPSCs) were recorded simultaneously using Fura-2 fluorescence and whole-cell patch-clamp respectively. The Ca²⁺ signals and eIPSCs were evoked by direct extracellular electrical stimulation of a single presynaptic terminal by short depolarising pulses. The presynaptic Ca²⁺ transient was graded by varying the amplitude of extracellular stimulating pulses. The probability of the release event, P, estimated for each stimulation strength, reached a maximum (P=1) when the Ca²⁺ signal became maximal and remained at this level at higher stimulation strength, despite the subsequent decrease in the amplitude of the Ca²⁺ transient. A gradual, linear increase in stimulation amplitude (V_stim) resulted in a bell-shaped dependence of the averaged amplitudes of Ca²⁺ signals and corresponding averaged amplitudes of eIPSCs. Analysis of the eIPSC demonstrated that the decrease in both the mean eIPSC amplitude and the mean quantal content of release resulted from a reduction in the probability of multivesicular release, i.e. in the disappearance of failures and in the decrease of individual eIPSC amplitude. The Ca²⁺ signals of similar amplitude resulted in both random and determinate (non-random) neurotransmitter release. We conclude that depolarisation-induced elevation of [Ca²⁺]_i within the terminal is necessary but not sufficient for activation of vesicular release of neurotransmitter.     

Functionally active complement proteins C6 and C7 detected in C6- and C7-deficient individuals

Two sensitive sandwich ELISAs based on monoclonal antibodies directed to native C6 and C7 allowed the detection and quantitation of these complement proteins in 20 out of 37 serum samples from individuals who had previously been classified as deficient in these proteins as assessed by immunochemical and/or functional assays. Furthermore, serum from four C6-deficient and one combined C6-/C7-deficient individual showed an increase in the terminal complement complex (TCC) and a decrease in native C6 and C7 after complement activation as assayed by specific ELISAs. Despite their (incomplete) deficiencies, these individuals therefore possess functionally active terminal complement proteins with respect to their ability to generate the TCC. As these individuals have no history of a susceptibility to neisserial infections, even low concentrations of functionally active C6 and C7 may provide sufficient protection against those micro-organisms whose destruction requires TCC formation.     

The dendritic architecture of the medial terminal nucleus of the accessory optic system in the rat,rabbit, and cat

Summary The neurons of the medial terminal nucleus (MTN) of the accessory optic system (AOS) have been studied in the rat, rabbit and cat in Golgi-Cox and Golgi-Kopsch impregnated brain sections. The present anatomical findings permit a division of the MTN of these species into dorsal and ventral components (MTNd, MTNv), in agreement with other investigations. The MTNd contains predominantly linear-bipolar and linear-multipolar shaped neurons with cell bodies that measure in the range of 25–50 m. These neurons have 2 to 4 primary dendrites which, along with their smaller dendritic branches, are oriented in the plane of the long axis of the MTN (i.e. from ventromedial to dorsolateral). These linear-bipolar and linear-multipolar cells represent 70–80% of the neurons of the MTNd as seen in the Golgi impregnated sections. The remaining 20–30% of the MTNd neurons are nearly all multipolar in shape with somata measuring in the range of 15–25 m. An occasional multipolar neuron is larger, has a soma that measures around 30–60 m and has dendrites which extend outward from the cell body to cover large areas of the MTNd. There was considerable extension of the dendrites of MTNd neurons into the MTNv; however, the dendrites of MTNd neurons were not observed extending into the adjacent substantia nigra (SN) or ventral tegmental area (VTA) of Tsai (1925). Conversely, the dendrites of neurons in the neighboring SN and VTA course along the borders of the MTN but only occasionally extend into the MTN. The neuron population of the MTNv consists almost entirely of small-multipolar shaped cells with somata measuring from 15–25 m and dendritic trees resembling those described for multipolar cells of the MTNd. A small number of neurons of the ventral division are medium-multipolar in shape with cell bodies that measure approximately 30–60 m. Typically, these cells have several dendrites which extend ventrally within the MTNv and one or more dendrites that extend either across the MTNv or dorsally into the MTNd. Only a few linear-bipolar and linear-multipolar neurons were observed in the MTNv. The present findings are discussed in relation to anatomical, physiological, and histochemical studies on the MTN.Abbreviations to Figures CP Cerebral Peduncle - DTN Dorsal Terminal Nucleus - LG Lateral Geniculate Nucleus - LP Lateral Posterior Nucleus - MG Medial Geniculate Nucleus - ML Medial Lemniscus - MTNd Medial Terminal Nucleus, dorsal division - MTNv Medial Terminal Nucleus, ventral division - NTO Nucleus of the Optic Tract - PA Anterior Pretectal Nucleus - pn Nucleus Paranigralis - PP Posterior Pretectal Nucleus - Pul Pulvinar - PO Olivary Pretectal Nucleus - RN Red Nucleus - SGS Stratum Griseum Superficiale, Superior Colliculus - SN Substantia Nigra Supported by USPHS research grant EYO3642 from the National Eye Institute