南京“5.7”192Ir源放射事故患者早期物理剂量估算

目的 对南京"5.7"¹⁹²Ir源放射事故中,1例局部受大剂量外照射的患者的受照剂量进行快速估算。方法 在获知放射源参数、照射方式和照射时间的基础上,基于东亚人体素体模和受照者主要生理特征,利用蒙特卡罗模拟软件包MCNP建立模型并估算。结果 估算了受照患者16个器官的吸收剂量,数值范围为0.03~9.16 Gy。腿部皮肤的等剂量曲线清晰显示了左、右腿部皮肤的剂量差异。受照者睾丸、前列腺受照剂量较大,吸收剂量数值约9.16 Gy。大腿皮肤受到局部大剂量照射,双腿皮肤剂量估算结果与红外热成像仪探测结果基本一致。结论 结合恰当受照模型的蒙特卡罗技术和模拟软件包可有效用于放射事故患者的早期物理剂量估算。     

Emergence of spatial impairment in rats following specific cholinergic depletion of the medial septum combined with chronic stress

A consistent finding in patients suffering from Alzheimer's disease is a loss of the cholinergic neurons of the basal forebrain that project to the hippocampus. However, the role this depletion plays in the development of Alzheimer's disease remains unclear. The loss of this ascending neurotransmitter system could potentially render hippocampal neurons more susceptible to further insult, such as chronic stress, ultimately resulting in neuronal death and memory loss. We explored this possibility by using the highly specific toxin 192 IgG-Saporin to destroy the majority of cholinergic activity in the septo-hippocampal pathway in rats. Following depletion, rats were subjected to 2 weeks of restraint stress. Rats were divided into two groups and were tested either on a hippocampal-dependent (water maze) task or a hippocampal-independent task (fear conditioning to tone and context). We showed that cholinergic depletion or stress alone had no effect on the successful performance of either of the tasks. However, rats with a combination of cholinergic depletion and stress were significantly impaired on the water-maze task. No deficits were apparent in the combined group that was tested on fear conditioning to tone or context, suggesting that this impairment is specific to spatial working memory. These rats had no obvious hippocampal neuronal loss or damage; however, there were likely subtle changes in hippocampal processing that led to the observed deficit on the hippocampal-dependent task. These findings support our theory that cholinergic depletion of the medial septum increases hippocampal vulnerability to further insults such as stress.     

Reduced cholinergic status in hippocampus produces spatial memory deficits when combined with kainic acid induced seizures

Alzheimer's disease is the most common form of dementia in North America today. Though many risk factors have been suggested to increase the likelihood of developing this disease, an accurate etiology has yet to be described. One of these risk factors commonly associated with Alzheimer's disease is the loss of cholinergic neurons of the medial septum that project to the hippocampus, leading to depletion in cholinergic activity. A second risk factor is the presence of seizures, which can increase the risk of excitotoxic cell death. To examine the interaction between these two common risk factors, we gave rats a focal cholinergic lesion of the medial septum using the specific immunotoxin 192-IgG Saporin, followed 2 weeks later by a non-convulsive dose of kainic acid. We then assessed the rats for seizure severity, hippocampal damage and performance on a spatial memory task. The combination of the two factors resulted in a trend towards increased seizure severity in the cholinergic depleted rats, but more importantly, the lesioned rats that had non-convulsive seizures were significantly impaired on a spatial version of the Morris water maze when compared with either the rats with a cholinergic depletion or non-convulsive seizure alone. This result could not be explained by seizure severity or the extent of hippocampal damage, suggesting a more subtle interaction between these two risk factors in the development of a hippocampal based memory impairment.     

microRNA-192在结直肠癌中的表达及意义

目的 探讨microRNA-192在结直肠癌组织中的表达及意义.方法 选取2010-01—2014-12南方医科大学附属东莞医院手术切除的结直肠癌患者45例,腺瘤25例,增生性息肉25例.采用荧光定量PCR技术检测上述组织中microRNA-192的表达水平.利用脂质体将microRNA-192模拟物瞬时转染至人肠癌细...     

Expression of Amyloid precursor protein, tau and presenilin RNAs in rat hippocampus following deafferentation lesions

In this study, entorhinal cortex lesions and/or medial septal area cholinergic lesions were used in the rat to mimic some of the principal and earliest affects in Alzheimer's disease, namely hippocampal deafferentation. We wished to test the hypothesis that deafferentation lesions cause changes in the regulation of three proteins that are known to be important in Alzheimer's disease pathology, namely amyloid precursor protein, presenilin and tau. Expression of amyloid precursor protein mRNA was increased in several subfields of hippocampus when examined 1 week after entorhinal cortex lesion, but was reduced, compared to sham operated controls, after medial septal area cholinergic lesions. Cholinergic lesions were combined with entorhinal cortex lesions and produced no change in APP mRNA levels compared to controls. No significant changes were observed in the parietal cortex after entorhinal cortex or cholinergic lesions either alone or in combination. Tau mRNA level in hippocampus was unchanged after lesions. Presenilin-1 mRNA was expressed in the hippocampus at very low levels, and appeared to be increased following entorhinal cortex lesion. Our results support the hypothesis that amyloid precursor protein expression in hippocampal neurons is differentially affected by glutamatergic and cholinergic afferent input, and that presenilin-1, but not tau, may be subject to the same type of control in vivo.     

Planning of Ir-192 seed implants for boost irradiation to the breast

The conservative management of early stage breast cancer with tumor excision and irradiation of the breast is becoming increasingly accepted as an alternative to modified radical mastectomy. The radiotherapy typically consists of 45 to 50 Gy delivered with external beam irradiation, followed by boost irradiation of 15 to 20 Gy to the tumor bed using electron beams or interstitial implantation. Pathological evaluation of the excised tumor, clinical assessment, and mammography are used to determine the tissue volume potentially containing a residual tumor burden and therefore requiring boost irradiation. In this paper we describe planning and implantation procedures for Quimby-type breast implants using Ir-192 seeds encapsulated in nylon tubing. This system deviates in several important respects from the requirements of the standard brachytherapy systems. For double-plane implants, optimized values of the interplanar spacing are given for a range of implant sizes, along with the corresponding target dose rates for 1.0 mCi seeds. We also describe a modification of the angiocatheter implantation technique, which allows the radioactive sources to be secured in place by a magnetic cap and washer, thus greatly facilitating the removal of the sources at the end of treatment.     

Selective changes in hippocampal neuropeptide Y neurons following removal of the cholinergic septal inputs

The number and distribution of subpopulations of hilar interneurons containing neuropeptide Y (NPY), somatostatin (SOM), or γ-aminobutyric acid (GABA) immunoreactivities were examined in the hilus of the dentate gyrus following removal of the cholinergic septal inputs. One, 2, 4, 8, 12, and 24 weeks after intracerebroventricular injections of immunotoxin, consisting of antibody to the low-affinity nerve growth factor receptor conjugated to saporin (192 IgG-saporin), lesioned rats were processed simultaneously with controls for NPY, SOM, or GABA immunolabeling. Across all time points, the number of NPY-labeled neurons was reduced to a statistically significant level (paired t-test, P = 0.001) in the injected rats (73% of control values, on average). The decrease in the number of NPY-labeled neurons was not limited to any particular subregion rostrally but appeared greater in the central region caudally. The size of NPY-labeled neurons did not differ statistically between control and immunolesioned rats examined at 1, 2, and 24 week time points. In contrast, the number of both SOM- and GABA-immunoreactive neurons in injected rats did not appear to be affected in any consistent manner. Examination of the hilus in adjacent Nissl-stained sections with the optical dissector revealed that although the total number of small nonprincipal cells (5–15 μm in diameter) did not appear affected at the 4-week time point, there was a statistically significant (P = 0.03) reduction across the 8–24-week time points (to 80% of control values, on average). Dual-labeling studies on separate rats showed that a small subpopulation of the NPY- and SOM-labeled neurons, primarily in the infragranular hilus, were colocalized with neurons containing GABA immunoreactivity (18% and 5%, respectively). These studies demonstrate that removal of the cholinergic septal inputs (1) can cause relatively rapid, selective decreases in the number of NPY-immunoreactive hippocampal interneurons and (2) appears to lead to the death of hippocampal interneurons over a longer time course. The changes in NPY immunoreactivity seem to occur in the portion of interneurons that probably does not contain either SOM or GABA immunoreactivity. J. Comp. Neurol. 386:46–59, 1997. © 1997 Wiley-Liss, Inc.     

Potentiation of glutamatergic EPSPs in rat CA1 hippocampal neurons after selective cholinergic denervation by 192 IgG-saporin

A complete and selective destruction of the basal forebrain cholinergic neurons projecting to the cerebral cortex and the hippocampus was induced in the rat by the toxin 192 IgG-saporin. Using electrophysiologic techniques, we have investigated the consequences of this cholinergic denervation on inhibitory and excitatory synaptic responses of CA1 pyramidal cells in rat hippocampal slices ex vivo. Histochemical experiments were performed in slices from control and 192 IgG-saporin–treated rats to check the efficacy of the intracerebroventricular injection of the immunotoxin. Stimulation of stratum radiatum elicits a glutamatergic excitatory postsynaptic potentials followed by a biphasic GABAergic inhibitory postsynaptic potential (IPSP). No significant change in IPSP was observed in 192 IgG-saporin–treated rats. By contrast, the N-methyl-d-aspartate (NMDA) and to a lesser extent the non-NMDA components of the glutamatergic response were potentiated in these animals. The possible pre- and postsynaptic mechanisms of this potentiation were discussed. Synapse 26:292–300, 1997. © 1997 Wiley-Liss Inc.     

Selective immunolesions of hippocampal cholinergic input fail to impair spatial working memory

The septo-hippocampal cholinergic pathway has traditionally been thought of as essential for spatial memory. Recent studies have demonstrated intact spatial learning following removal of this pathway with an immunotoxin selective for cholinergic neurons. In the present experiment, rats with selective removal of hippocampal cholinergic input were tested in a delayed nonmatching-to-position task in a water version of the radial arm maze. This allowed us to increase and parametrically vary the memory load compared with the standard Morris water maze (by varying the delay between the initial four choices and the final four choices) to determine if this would reveal a deficit in rats with lesions of septo-hippocampal cholinergic projections. Male Long-Evans rats were given injections of 192 lgG-saporin, a selective immunotoxin for cholinergic neurons, into the medial septum/vertical limb of the diagonal band (MS/VDB) to remove cholinergic projections to the hippocampus, or a control surgery. The rats were trained on the radial maze task following surgery. An escape platform was located at the end of each arm of the maze and was removed after an arm was utilized for escape. After initial training, a delay was interposed between the first four trials and the second four trials. Errors during the second four-trial component were scored in two categories: retroactive (reentering an arm chosen before the delay) and proactive (reentering an arm chosen after the delay). Retroactive errors increased as delay increased (from 60 s to 6 h) but were equivalent in control and MS/VDB-lesion groups. Proactive errors did not vary with delay and were also unaffected by the lesion. Radioenzymatic assays for choline acetyltransferase activity in the hippocampus of lesioned rats confirmed a significant loss of cholinergic input from the MS/VDB. These results indicate that normal spatial working memory is possible after substantial loss of septo-hippocampal cholinergic projections. Hippocampus 7:130–136, 1997. © 1997 Wiley-Liss, Inc.