Endovascular management of intracranial aneurysms during pregnancy in three cases and review of the literature

We present three cases of cerebral aneurysms (1 unruptured; 2 ruptured) treated with endovascular techniques in pregnancies. The first ruptured case is a 28-year-old female on 20th gestational week. After the endovascular coiling, the patient suffered persistent hemiparesis and delivered a healthy baby by cesarean section. The second ruptured case is a 25-year-old female on 36th week of pregnancy. She died of aneurysm re-rupture after delivery of a healthy baby by cesarean section. The third unruptured case is a 31-year-old woman on the 26th gestational week of pregnancy who died of a giant basilar tip aneurysm after stent-assisted coiling. Ruptured aneurysm obliteration should be prioritized followed by vaginal delivery or cesarean section. The decision regarding the treatment of unruptured aneurysms should be carefully considered on a case-by-case basis. Stent-assisted coiling may be applicable to aneurysm during pregnancy.     

Anatomic variations of internal jugular vein,inferior petrosal sinus and its confluence pattern: Implications in inferior petrosal sinus catheterization

Objective

The purpose of this study is to describe anatomic variations of the internal jugular vein (IJV), inferior petrosal sinus (IPS) and their confluence pattern and implications in IPS catheterization. The anatomic route of IPS after going out of the cranium and its confluence patterns with IJV and will supply knowledge about typing of IPS-IJV junction.

Method

A review of the literature was performed.

Results

There might be different routes for entering the intracranial segment of the IPS and multislice spiral computed tomography (MSCT) is effective in identifying the confluences of the IPS with the IJV and their courses. It is important to find the confluence of IPS with IJV for diagnosis and treatment of intracranial lesions via venous route. Meanwhile, IPS diameter at the confluence can significantly affect success of catheterization.

Conclusion

The classification and the theory of the development of the caudal end of the IPS may be useful in establishing treatment strategies that involve endovascular manipulation via the IPS.     

IL-2诱导类风湿关节炎与骨关节炎T淋巴细胞STAT3 STAT5酪氨酸磷酸化状态的比较

目的观察白细胞介素(IL)-2作用于类风湿关节炎(RA)与骨关节炎(OA)外周血T淋巴细胞前后,T淋巴细胞中STAT3及STAT5的酪氨酸磷酸化活化状态,并进行比较.方法从RA与OA患者的外周血中分离培养单个核细胞,继而纯化得到T淋巴细胞,静息后,用重组人IL-2刺激,在各时相裂解细胞,收获提取蛋白,进行Western blot分析.结果在静息后,RA与OA的外周血T淋巴细胞中STAT3与STAT5均处于极低水平磷酸化的状态;在IL-2作用后,T淋巴细胞中STAT3和STAT5发生时相性的酪氨酸磷酸化,而RA的T淋巴细胞磷酸化程度较OA显著增高.结论IL-2对RA患者T淋巴细胞的STAT3和STAT5过度激活,引起T淋巴细胞中IL-2信号传导的异常放大效应,可能在RA的发病过程中发挥重要作用.     

Etiology of distinct membrane excitability in pre- and posthearing auditory neurons relies on activity of Cl? channel TMEM16A

The developmental rehearsal for the debut of hearing is marked by massive changes in the membrane properties of hair cells (HCs) and spiral ganglion neurons (SGNs). Whereas the underlying mechanisms for the developing HC transition to mature stage are understood in detail, the maturation of SGNs from hyperexcitable prehearing to quiescent posthearing neurons with broad dynamic range is unknown. Here, we demonstrated using pharmacological approaches, caged-Ca²⁺ photolysis, and gramicidin patch recordings that the prehearing SGN uses Ca²⁺-activated Cl⁻ conductance to depolarize the resting membrane potential and to prime the neurons in a hyperexcitable state. Immunostaining of the cochlea preparation revealed the identity and expression of the Ca²⁺-activated Cl⁻ channel transmembrane member 16A (TMEM16A) in SGNs. Moreover, null deletion of TMEM16A reduced the Ca²⁺-activated Cl⁻ currents and action potential firing in SGNs. To determine whether Cl⁻ ions and TMEM16A are involved in the transition between pre- and posthearing features of SGNs we measured the intracellular Cl⁻ concentration [Cl⁻]_i in SGNs. Surprisingly, [Cl⁻]_i in SGNs from prehearing mice was ∼90 mM, which was significantly higher than posthearing neurons, ∼20 mM, demonstrating discernible altered roles of Cl⁻ channels in the developing neuron. The switch in [Cl⁻]_i stems from delayed expression of the development of intracellular Cl⁻ regulating mechanisms. Because the Cl⁻ channel is the only active ion-selective conductance with a reversal potential that lies within the dynamic range of SGN action potentials, developmental alteration of [Cl⁻]_i, and hence the equilibrium potential for Cl⁻ (E_Cl), transforms pre- to posthearing phenotype.The dynamic range of neuronal action potentials (APs) resides within voltages that are outside the reversal potentials (E_rev) of most ion currents except Cl⁻ currents, making Cl⁻ conductance the most versatile one in a course of a single AP. Neurons use this adaptable feature of Cl⁻ conductance with respect to the resting membrane potential (RMP) of neurons to confer synaptic plasticity by altering intracellular Cl⁻ (Cl⁻_i) homeostasis during development. This process transforms depolarizing GABA/glycinergic-mediated responses in immature to hyperpolarizing responses in mature neurons (1, 2). A similar synaptic switch has been described in auditory brainstem neurons, where the mature GABA/glycinergic-induced inhibitory neurotransmission contributes strongly toward the computation of interaural level and time differences required for sound source localization (3–6). The depolarization mediated by GABA/glycine in early postnatal development may increase intracellular Ca²⁺ concentration ([Ca²⁺]_i), which is predicted to promote synapse stabilization in the CNS (1). We hypothesized that besides synaptic plasticity one mechanism that alters the firing phenotype of developing neurons is via changes in intracellular Cl⁻ concentration ([Cl]_i) and activation of voltage and Ca²⁺-activated Cl⁻ channels (CaCCs).CaCCs are encoded by anoctamin 1 and 2 (ANO1 and 2), also known as transmembrane member 16A and B (TMEM16A and B) genes, which are expressed in epithelia and smooth muscle cells (7, 8) and in sensory cells such as nociceptive dorsal root ganglion neurons (9, 10), cilia of olfactory cells (11), and in rods and cones (12). The prevailing functions of CaCCs are ascribed to the amplification of pain sensation (10), cone responses (12), and olfactory signal transduction (13, 14), although recent reports using TMEM16B knockout mice suggest that CaCCs may play a limited role in signal amplification of olfactory transduction (11). TMEM16A has been identified in the cochlea in a cell-type-specific manner, showing robust labeling in basal cells of the stria vascularis and efferent endings of the auditory nerve (15), but its role in the inner ear has not been determined.The trademark of the developing auditory neuron is the rhythmic and burst-patterned spontaneous AP (SAP), which is thought to shape synapse formation and refinement in the brainstem (16, 17). In the inner ear, inputs from Ca²⁺-mediated SAPs from developing hair cells (HCs) sculpt the firing patterns of spiral ganglion neurons (SGNs) (18, 19). However, SGNs evolve from depolarizing hyperexcitable to hyperpolarized mature neurons with a wide dynamic range (20). Mechanisms underlying the remarkable changes in SGN phenotype during development are not well understood. Here, we demonstrate the origin and molecular mechanisms of the transition from primordial to mature auditory neurons. SGNs undergo marked alterations in intracellular Cl⁻ concentration ([Cl⁻]_i) handling during development and in doing so transform a predominantly inwardly driven Cl⁻ current into outwardly directed current through activation of TMEM16 channels.     

Cell membrane gp96 facilitates HER2 dimerization and serves as a novel target in breast cancer

HER2 receptor dimerization is a critical step in the HER2 activation process. Here, we demonstrated that heat shock protein gp96 on cell membrane interacts with HER2, facilitates HER2 dimerization and promotes cell proliferation. Cell membrane gp96 levels were observed to correlate with HER2 phosphorylation in primary breast tumors. Finally, we provide evidence that targeting gp96 with a specific monoclonal antibody led to decreased cell growth and increased apoptosis in vitro, and suppression of tumor growth in vivo. Our work represents a new therapeutic strategy for inhibiting HER2 signaling in cancer.     

血管内皮生长因子和基质金属蛋白酶-2在上皮性膀胱癌组织中的表达

目的：探讨上皮性膀胱癌组织中血管内皮生长因子（VEGF）和基质金属蛋白酶-2（MMP-2）的表达及临床意义。方法采用免疫组化S-P法检测67例上皮性膀胱癌及其癌旁组织中VEGF和MMP-2的表达,并分析两者与患者临床病理特征的关系。结果上皮性膀胱癌组织中VEGF和MMP-2的表达均高于癌旁组织（ P均＜0.05）。上皮性膀胱癌组织中VEGF和MMP-2的表达与其病理分级和临床分期有关（ P均＜0.05）。上皮性膀胱癌组织中VEGF和MMP-2的表达呈正相关关系（ r=0.468,P＜0.05）。结论上皮性膀胱癌组织中VEGF和MMP-2高表达,两者可能参与了上皮性膀胱癌的疾病进展。