Multiple Familial Trichoepithelioma with Malignant Transformation

Trichoepithelioma (TE) is a benign tumor of follicular origin that presents as small, skin-colored papules predominantly on the face. When more than one family member is affected, the disease is known as multiple familial trichoepithelioma (MFT). It is a rare autosomal dominant (AD) skin disease. Malignant transformation is very rare. We present a case of MFT in a female patient and her father with malignant transformation to basal cell carcinoma (BCC) in the father. We summarized the main histological differential parameters between TE and BCC and applied immunophenotyping for both by administration of Bcl2, CD34, CD10 and androgen receptor (AR) antibodies.     

翼点切口侧裂-岛叶入路治疗基底节脑出血

目的 探讨显微镜下经侧裂-岛叶清除基底节区脑内出血,脑组织及血管保护.方法 回顾性分析近两年经岛叶入路,显微镜下血肿清除术治疗29例基底节区脑出血患者临床资料.结果 术后1h、24 h、7d复查头颅CT,血肿清除率＞90％ 21例、＞80％8例,再出血1例.ADL评分Ⅰ级4例,Ⅱ级10例,Ⅲ级13例,Ⅳ级2例.结论 翼点经侧裂岛叶入路有利于保护神经和血管组织.     

Tractographical model of the cortico‐basal ganglia and corticothalamic connections

The cortico‐basal ganglia and corticothalamic projections have been extensively studied in the context of neurological and psychiatric disorders. Deep brain stimulation (DBS) is known to modulate many of these pathways to produce the desired clinical effect. The aim of this work is to describe the anatomy of the main circuits of the basal ganglia using tractography in a surgical planning station. We used imaging studies of 20 patients who underwent DBS for movement and psychiatric disorders. We segmented the putamen, caudate nucleus (CN), thalamus, and subthalamic nucleus (STN), and we also segmented the cortical areas connected with these subcortical areas. We used tractography to define the subdivisions of the basal ganglia and thalamus through the generation of fibers from the cortical areas to the subcortical structures. We were able to generate the corticostriatal and corticothalamic connections involved in the motor, associative and limbic circuits. Furthermore, we were able to reconstruct the hyperdirect pathway through the corticosubthalamic connections and we found subregions in the STN. Finally, we reconstructed the cortico‐subcortical connections of the ventral intermediate nucleus, the nucleus accumbens and the CN. We identified a feasible delineation of the basal ganglia and thalamus connections using tractography. These results could be potentially useful in DBS if the parcellations are used as targets during surgery. Clin. Anat. 29:481–492, 2016. © 2016 Wiley Periodicals, Inc.     

Axon growth-promoting properties of human bone marrow mesenchymal stromal cells

Mesenchymal stromal cells are promising candidate donor cells for promoting functional tissue repair following traumatic spinal cord injury (SCI), however, the mechanism(s) of action remain poorly defined. Here, we describe an in vitro study of the axon growth-promoting properties of highly enriched populations of adult human mesenchymal stromal cells (hMSC). A random, non-oriented pattern of neuritic outgrowth was observed from dissociated adult rat DRG neurons seeded onto confluent A431 cells and PLL/laminin positive control substrata. Confluent hMSC formed arrays of similarly orientated cell bodies and processes which supported the regeneration of significantly more primary neurites but a slightly lower overall neuritic length than was observed over the PLL/laminin control substrate. The hMSC exerted a strong influence on the direction of neuritic outgrowth, with many regenerating processes following the orientation of underlying hMSC. The production of extracellular matrix appeared to be responsible for neuritic directionality, but the release of growth factors was a significant promoter for DRG neuritic outgrowth. This suggests that further investigations into the properties of hMSC may be of particular interest in the development of transplant-mediated strategies intending to promote functional axonal regeneration after SCI.     

The role of the superior colliculus in predatory hunting

Combining the results of behavioral, neuronal immediate early gene activation, lesion and neuroanatomical experiments, we have presently investigated the role of the superior colliculus (SC) in predatory hunting. First, we have shown that insect hunting is associated with a characteristic large increase in Fos expression in the lateral part of the intermediate gray layer of the SC (SCig). Next, we have shown that animals with bilateral NMDA lesions of the lateral parts of the SC presented a significant delay in starting to chase the prey and longer periods engaged in other activities than predatory hunting. They also showed a clear deficit to orient themselves toward the moving prey and lost the stereotyped sequence of actions seen for capturing, holding and killing the prey. Our Phaseolus vulgaris-leucoagglutinin analysis revealed that the lateral SCig, besides providing the well-documented descending crossed pathway to premotor sites in brainstem and spinal cord, projects to a number of midbrain and diencephalic sites likely to influence key functions in the context of the predatory behavior, such as general levels of arousal, motivational level to hunt or forage, behavioral planning, appropriate selection of the basal ganglia motor plan to hunt, and motor output of the primary motor cortex. In contrast to the lateral SC lesions, medial SC lesions produced a small deficit in predatory hunting, and compared to what we have seen for the lateral SCig, the medial SCig has a very limited set of projections to thalamic sites related to the control of motor planning or motor output, and provides conspicuous inputs to brainstem sites involved in organizing a wide range of anti-predatory defensive responses. Overall, the present results served to clarify how the different functional domains in the SC may mediate the decision to pursue and hunt a prey or escape from a predator.     

内镜手术治疗基底节区高血压脑出血的效果观察

目的 探讨内镜手术治疗基底节区高血压脑出血的效果。方法 选择2018年7～12月在我院诊断治疗的基底节区高血压脑出血患者60例的临床资料进行回顾性分析。其中30例患者采用神经内镜下手术治疗为内镜组,30例患者采用小骨窗手术治疗为对照组。比较两组的手术时间、术后残余血量、血肿清除率、再出血率、术前及术后24 h GCS评分,术后6个月GOS预后评价。结果 (1)内镜组手术时间显著短于对照组,残余血肿量显著低于对照组,血肿清除率显著高于对照组,差异有统计学意义(P0.05);两组再出血率比较,差异无统计学意义(P0.05)。(2)两组治疗后24 h GCS评分较治疗前显著提高,差异有统计学意义(P0.05);治疗后内镜组GCS评分显著高于对照组,差异有统计学意义(P0.05)。(3)秩和检验显示,内镜组GOS预后评价显著优于对照组,差异有统计学意义(P0.05)。结论 内镜下手术治疗基底节区高血压脑出血操作相对简单,创伤更小,术中出血量少,血肿清除率高,术后24 h GCS评分更好,术后6个月GOS评分更好,说明该方法创伤小,血肿清除率高,术后近期及远期预后更好。     

显微镜下无牵拉技术经侧裂-岛叶入路治疗基底节区高血压脑出血的临床研究

目的 探讨显微镜下无牵拉技术经侧裂-岛叶入路治疗基底节区高血压脑出血的临床价值。方法 选择丽水市人民医院2017年2月～2019年1月收治的基底节区高血压脑出血患者74例为研究对象,按照患者入院后病床尾号单双原则分为对照组(单号37例)与观察组(双号37例)。对照组采用单纯血肿腔制管引流,观察组采用显微镜下无牵拉技术经侧裂-岛叶入路治疗,比较两组患者手术效果、术后并发症发生情况;对患者进行为期6个月随访,比较两组患者格拉斯哥预后(GOS)、日常生活活动能力(ADCS-ADL)情况。结果 观察组手术时间长于对照组,血肿清除率高于对照组,意识恢复时间、住院时间短于对照组,差异有统计学意义(P0.05);观察组术后再出血、水电解质紊乱、肺部感染发生率明显低于对照组,观察组未发生颅内感染,对照组发生6例颅内感染(16.22%),差异有统计学意义(P0.05);观察组术后1个月、6个月GOS评分、ADCS-ADL评分均明显高于对照组,差异有统计学意义(P0.05)。结论 显微镜下无牵拉技术经侧裂-岛叶入路治疗基底节区高血压脑出血效果肯定,能显著提升血肿清除率,减少术后并发症发生率,缩短患者意识恢复时间及住院时间,改善患者预后及日常生活活动能力。     

DNA repair synthesis in fibroblast strains from patients with actinic keratosis,squamous cell carcinoma,basal cell carcinoma,or malignant melanoma after treatment with ultraviolet light,N-acetoxy-2-acetyl-aminofluorene,methyl methanesulfonate,and N-methyl-N-nitrosourea

Summary Fibroblast strains derived from skin biopsies of patients with actinic keratosis (6), malignant melanoma (18), squamous cell carcinoma (11), and basal cell carcinoma (12) were investigated for DNA repair synthesis, with 16 fibroblast strains for normal donors as controls. Cells were exposed to UV light, the UV-like carcinogen (Ac)₂ONFln, and the methylating carcinogenes MeSO₂OMe and MeNOUr. Dose-response experiments, which included 10 dose levels, were performed, the data analyzed by linear regression, and the slope of the regression line (term: G ₀) used as a measure of DNA repair synthesis. The mean experimental variability of G ₀ of individual fibroblast strains was 9.5%–15.4%, depending upon exposure. For comparison of all cell strains belonging to the same skin malignancy group with those of the control group, G ₀ values of the individual strains were combined to yield group-specific weighted mean G ₀ values.In addition, the capacity to incise UV-damaged DNA was measured in 24 cell strains from patients with skin tumors using the alkaline elution technique. For quantitating DNA-incising capacity, the initial velocities of the elution curves were plotted versus the UV dose, and the slope of the resulting regression line was used to obtain the characteristic value E ₀. The mean experimental variability of E ₀ of individual strains was ±22%. These E ₀ values were combined to yield weighted mean values of groups.The fibroblast strains in the groups of patients with actinic keratosis and malignant melanoma were found to have normal mean G ₀ values when DNA repair synthesis was challenged with UV light or one of the three carcinogens. However, the squamous cell carcinoma group exhibited significantly lower mean G ₀ values after treatment with UV light (82% that of normal donors), (Ac)₂ONFln (70%), MeSO₂OMe (70%), and MeNOUr (69%). The basal cell carcinoma group showed significantly diminished repair synthesis upon treatment with UV light (81% that of normal donors) and MeSO₂OMe (67%). In contrast to these findings, in no skin malignancy group was post UV DNA-incising capacity (E ₀) significantly diminished, although it should be noted that group sizes were only half as large as for G ₀ determinations.These data may be interpreted as indicating that DNA excision repair is impaired in fibroblast strains from patients with squamous cell carcinoma and — to a lesser extent — basal cell carcinoma. This deficiency seems to pertain to several DNA repair mechanisms, as excision of both alkylation and UV-induced damage is involved. Although the repair impairments are statistically significant, the relative risks at which the investigated patients are do not seem to be high enough as to be of immediate practical value. Our results indicate further studies would be useful.Abbreviations XP xeroderma pigmentosum - UV light ultraviolet light - UVB UV light with the wavelength from 290 nm to 320 nm - (Ac)₂ONFln N-acetoxy-2-acetylaminofluorene - MeSO₂OMe methyl methanesulfonate - MeNOUr N-methyl-N-nitrosourea - ara-C 1--d-arabinofuranosyl cytosine This work was supported by the Deutsche Forschungsgemeinschaft, SFB 136Dedicated to Professor E. Hecker on the occasion of his 60th birthday     

Role of PKA signaling in D2 receptor-expressing neurons in the core of the nucleus accumbens in aversive learning

The nucleus accumbens (NAc) serves as a key neural substrate for aversive learning and consists of two distinct subpopulations of medium-sized spiny neurons (MSNs). The MSNs of the direct pathway (dMSNs) and the indirect pathway (iMSNs) predominantly express dopamine (DA) D1 and D2 receptors, respectively, and are positively and negatively modulated by DA transmitters via Gs- and Gi-coupled cAMP-dependent protein kinase A (PKA) signaling cascades, respectively. In this investigation, we addressed how intracellular PKA signaling is involved in aversive learning in a cell type-specific manner. When the transmission of either dMSNs or iMSNs was unilaterally blocked by pathway-specific expression of transmission-blocking tetanus toxin, infusion of PKA inhibitors into the intact side of the NAc core abolished passive avoidance learning toward an electric shock in the indirect pathway-blocked mice, but not in the direct pathway-blocked mice. We then examined temporal changes in PKA activity in dMSNs and iMSNs in behaving mice by monitoring Förster resonance energy transfer responses of the PKA biosensor with the aid of microendoscopy. PKA activity was increased in iMSNs and decreased in dMSNs in both aversive memory formation and retrieval. Importantly, the increased PKA activity in iMSNs disappeared when aversive memory was prevented by keeping mice in the conditioning apparatus. Furthermore, the increase in PKA activity in iMSNs by aversive stimuli reflected facilitation of aversive memory retention. These results indicate that PKA signaling in iMSNs plays a critical role in both aversive memory formation and retention.Aversive stimuli induce not only rapid avoidance behavior, but also memory formation to escape from uncomfortable environments, and thus strongly influence animal behavior (1–3). The mesolimbic dopaminergic (DA) system plays a critical role in both rapid aversive reaction and memory formation (3–5). The nucleus accumbens (NAc) receives DA inputs from the ventral tegmental area (VTA) and serves as a key neural substrate for the control of aversive learning (6–8). The NAc consists of two subpopulations of medium-sized spiny neurons (MSNs) (9–11). The MSNs of the direct pathway (dMSNs) send their axons to the substantia nigra pars reticulata (SNr) and VTA, and selectively express dopamine D1 receptors, whereas the MSNs of the indirect pathway (iMSNs) indirectly project to the SNr and VTA via the ventral pallidum (VP) and predominantly express D2 receptors (12, 13). D1 receptors stimulate the cAMP-dependent protein kinase A (PKA) signaling cascade via Gs and exhibit a low affinity for DA (14–16). Conversely, D2 receptors inhibit the cAMP-PKA cascade via Gi and show a high affinity for DA (14–16). Thus, these two distinct types of MSNs, constituting two parallel pathways, contribute to the dynamic modulation of neuronal cell excitability and synaptic plasticity in the NAc circuitry (14–16).Although accumulated evidence indicates that DA modulation of the NAc is critical for both reward-based and aversive reactions (3, 5, 6, 17), the response of DA neurons in the VTA to aversive stimuli is not uniform; that is, some DA neurons are stimulated in response to aversive stimuli, whereas most others react by transiently suppressing their firing (18–22). Recent optogenetic studies have revealed that not only activation of iMSNs, but also inactivation of the VTA neurons, which down-regulates DA levels in the NAc, evoke an aversive reaction and learning (23–26); however, how intracellular cAMP-PKA signaling is involved in the induction and retention of aversive memory in a cell type-dependent manner in the NAc circuit remains largely elusive.In the present investigation, we addressed this issue using two approaches. We first used asymmetric reversible neurotransmission blocking (aRNB) techniques (27, 28), in which either the direct or indirect pathway at one side of the NAc was selectively blocked by the pathway-specific expression of transmission-blocking tetanus toxin and the other intact side was manipulated by injection of PKA inhibitors. In the second approach, we examined temporal changes in PKA activities of these two pathways in the formation of aversive memory by monitoring Förster resonance energy transfer (FRET) responses of PKA selective for either dMSNs or iMSNs with the aid of in vivo microendoscopic analysis (29, 30). These two different approaches explicitly demonstrated that the activation of PKA in iMSNs plays a key role in both the formation and the retention of aversive memory.