Dissociation of Progressive Dopaminergic Neuronal Death and Behavioral Impairments by Bax Deletion in a Mouse Model of Parkinson's Diseases

Parkinson's disease (PD) is a common, late-onset movement disorder with selective degeneration of dopaminergic (DA) neurons in the substantia nigra (SN). Although the neurotoxin 6-hydroxydopamine (6-OHDA) has been used to induce progressive degeneration of DA neurons in various animal models of PD, the precise molecular pathway and the impact of anti-apoptotic treatment on this neurodegeneration are less understood. Following a striatal injection of 6-OHDA, we observed atrophy and progressive death of DA neurons in wild-type mice. These degenerating DA neurons never exhibited signs of apoptosis (i.e., caspase-3 activation and cytoplasmic release of cytochrome C), but rather show nuclear translocation of apoptosis-inducing factor (AIF), a hallmark of regulated necrosis. However, mice with genetic deletion of the proapoptotic gene Bax (Bax-KO) exhibited a complete absence of 6-OHDA-induced DA neuron death and nuclear translocation of AIF, indicating that 6-OHDA-induced DA neuronal death is mediated by Bax-dependent AIF activation. On the other hand, DA neurons that survived in Bax-KO mice exhibited marked neuronal atrophy, without significant improvement of PD-related behavioral deficits. These findings suggest that anti-apoptotic therapy may not be sufficient for PD treatment, and the prevention of Bax-independent neuronal atrophy may be an important therapeutic target

Arrhythmia surgery for atrial fibrillation associated with atrial septal defect: Right-sided maze versus biatrial maze

BackgroundAlthough it has been inferred that a biatrial maze procedure for atrial fibrillation in left-sided heart lesions may lead to better outcomes compared with a limited left atrial lesion set, it remains controversial whether the biatrial maze procedure is superior to the right atrial maze procedure in right-sided heart lesions.MethodsA retrospective review was performed for 56 adults who underwent surgical closure of atrial septal defect and various maze procedures for atrial fibrillation between June 1998 and February 2011. The median age at operation was 59 years (range, 34-79 years). Clinical manifestations of atrial fibrillation were paroxysmal in 8 patients, persistent in 15 patients, and long-standing persistent in 33 patients. A right atrial maze procedure was performed in 23 patients (group 1), and a biatrial maze procedure was performed in 33 patients (group 2). Treatment failure was defined as atrial fibrillation recurrence, development of atrial flutter or other types of atrial tachyarrhythmia, or implantation of a permanent pacemaker. The Cox proportional hazards model was used to identify risk factors for decreased time to treatment failure.ResultsDuring the median follow-up period of 49 months (range, 5-149 months), there was no early death and 1 late noncardiac death. On Cox survival model, group 1 showed a significantly decreased time to treatment failure in comparison with group 2 (hazard ratio, 5.11; 95% confidence interval, 1.59-16.44; P = .006). Maintenance of normal sinus rhythm without any episode of atrial fibrillation recurrence at 2 and 5 years postoperatively was 57% and 45% in group 1, respectively, and 82% and 69% in group 2, respectively.ConclusionsLeft-sided ablation in addition to a right atrial maze procedure leads to better electrophysiologic outcome in atrial fibrillation associated with atrial septal defect

An accurate method for quantifying and analyzing copy number variation in porcine KIT by an oligonucleotide ligation assay

<p>Abstract</p> <p>Background</p> <p>Aside from single nucleotide polymorphisms, copy number variations (CNVs) are the most important factors in susceptibility to genetic disorders because they affect expression levels of genes. In previous studies, pyrosequencing, mini-sequencing, real-time PCR, invader assays and other techniques have been used to detect CNVs. However, the higher the copy number in a genome, the more difficult it is to resolve the copies, so a more accurate method for measuring CNVs and assigning genotype is needed.</p> <p>Results</p> <p>PCR followed by a quantitative oligonucleotide ligation assay (qOLA) was developed for quantifying CNVs. The accuracy and precision of the assay were evaluated for porcine <it>KIT</it>, which was selected as a model locus. Overall, the root mean squares of bias and standard deviation of qOLA were 2.09 and 0.45, respectively. These values are less than half of those in the published pyrosequencing assay for analyzing CNV in porcine <it>KIT</it>. Using a combined method of qOLA and another pyrosequencing for quantitative analysis of <it>KIT </it>copies with spliced forms, we confirmed the segregation of <it>KIT </it>alleles in 145 F₁animals with pedigree information and verified the correct assignment of genotypes. In a diagnostic test on 100 randomly sampled commercial pigs, there was perfect agreement between the genotypes obtained by grouping observations on a scatter plot and by clustering using the nearest centroid sorting method implemented in PROC FASTCLUS of the SAS package. In a test on 159 Large White pigs, there were only two discrepancies between genotypes assigned by the two clustering methods (98.7% agreement), confirming that the quantitative ligation assay established here makes genotyping possible through the accurate measurement of high <it>KIT </it>copy numbers (>4 per diploid genome). Moreover, the assay is sensitive enough for use on DNA from hair follicles, indicating that DNA from various sources could be used.</p> <p>Conclusion</p> <p>We have established a high resolution quantification method using an oligonucleotide ligation assay to measure CNVs, and verified the reliability of genotype assignment for random animal samples using the nearest centroid sorting method. This new method will make it more practical to determine <it>KIT </it>CNV and to genotype the complicated <it>Dominant White/KIT </it>locus in pigs. This procedure could have wide applications for studying gene or segment CNVs in other species.</p

Serial CT Findings of Paragonimus Infested Dogs and the Micro-CT Findings of the Worm Cysts

OBJECTIVE: To investigate the serial CT findings of Paragonimus westermani infected dogs and the microscopic structures of the worm cysts using Micro-CT. MATERIALS AND METHODS: This study was approved by the committee on animal research at our institution. Fifteen dogs infected with P. westermani underwent serial contrast-enhanced CT scans at pre-infection, after 10 days of infection, and monthly thereafter until six months for determining the radiologic-pathologic correlation. Three dogs (one dog each time) were sacrificed at 1, 3 and 6 months, respectively. After fixation of the lungs, both multi-detector CT and Micro-CT were performed for examining the worm cysts. RESULTS: The initial findings were pleural effusion and/or subpleural ground-glass opacities or linear opacities at day 10. At day 30, subpleural and peribronchial nodules appeared with hydropneumothorax and abdominal or chest wall air bubbles. Cavitary change and bronchial dilatation began to be seen on CT scan at day 30 and this was mostly seen together with mediastinal lymphadenopathy at day 60. Thereafter, subpleural ground-glass opacities and nodules with or without cavitary changes were persistently observed until day 180. After cavitary change of the nodules, the migratory features of the subpleural or peribronchial nodules were seen on all the serial CT scans. Micro-CT showed that the cyst wall contained dilated interconnected tubular structures, which had communications with the cavity and the adjacent distal bronchus. CONCLUSION: The CT findings of paragonimiasis depend on the migratory stage of the worms. The worm cyst can have numerous interconnected tubular channels within its own wall and these channels have connections with the cavity and the adjacent distal bronchus

Pulmonary nodular ground-glass opacities in patients with extrapulmonary cancers: what is their clinical significance and how can we determine whether they are malignant or benign lesions?

BACKGROUND: The clinical significance of pulmonary nodular ground-glass opacities (NGGOs) in patients with extrapulmonary cancers is not known, although there is an urgent need for study on this topic. The purpose of this study, therefore, was to investigate the clinical significance of pulmonary NGGOs in these patients, and to develop a computerized scheme to distinguish malignant from benign NGGOs. METHODS: Fifty-nine pathologically proven pulmonary NGGOs in 34 patients with a history of extrapulmonary cancer were studied. We reviewed the CT scan characteristics of NGGOs and the clinical features of these patients. Artificial neural networks (ANNs) were constructed and tested as a classifier distinguishing malignant from benign NGGOs. The performance of ANNs was evaluated with receiver operating characteristic analysis. RESULTS: Twenty-eight patients (82.4%) were determined to have malignancies. Forty NGGOs (67.8%) were diagnosed as malignancies (adenocarcinomas, 24; bronchioloalveolar carcinomas, 16). Among the rest of the NGGOs, 14 were atypical adenomatous hyperplasias, 4 were focal fibrosis, and 1 was an inflammatory nodule. There were no cases of metastasis appearing as NGGOs. Between malignant and benign NGGOs, there were significant differences in lesion size; the presence of internal solid portion; the size and proportion of the internal solid portion; the lesion margin; and the presence of bubble lucency, air bronchogram, or pleural retraction (p < 0.05). Using these characteristics, ANNs showed excellent accuracy (z value, 0.973) in discriminating malignant from benign NGGOs. CONCLUSIONS: Pulmonary NGGOs in patients with extrapulmonary cancers tend to have high malignancy rates and are very often primary lung cancers. ANNs might be a useful tool in distinguishing malignant from benign NGGOs

A Large Cystic Phyllodes Tumor of the Prostate

We report a 65 year-old man with a large cystic phyllodes tumor of the prostate. The patient complained of abdominal discomfort and had a soft palpable mass. Computer tomography showed a solid and cystic mass in the pelvic fossa; the mass was adjacent only to the prostate. We excised the mass. Microscopic findings of the mass showed hyperplastic epithelium lined cysts with leaf-like intraluminal epithelia lined stromal projections, less than 2 mitotic counts/10 HPF, low-to-moderated cellularity, and mild-to-moderate cytoplasm atypia. The pathological findings were consistent with a phyllodes tumor of the prostate, a low-grade tumor. Twenty-eight months after the operation, the patient was well with no recurrence or metastases

Seborrheic Keratosis of the Conjunctiva: A Case Report

Seborrheic keratosis is a benign epithelial neoplasia that occurs mainly in the skin of the eyelids and face. We describe a case of seborrheic keratosis of the conjunctiva confirmed by histopathology. A 72-year-old man presented with a recurrent conjunctival mass involving the nasal side of his right eye. Clinically, a diagnosis of conjunctival papilloma was made, and a mass excision was performed. The histopathological analysis evidenced a conjunctival-covering epithelium with papillomatous changes and irregular acanthosis, at the expense of a proliferation of basaloid cells. In addition, the lesion exhibited multiple pseudohorn cysts containing keratin. With the above findings, a diagnosis of conjunctival seborrheic keratosis was established. The occurrence of seborrheic keratosis on the conjunctiva is rare. In this case, seborrheic keratosis was confirmed by pathologic report despite its similar appearance with papilloma. Seborrheic keratosis should be considered in the differential diagnosis of conjunctival lesions