Accumulation of L-type Bovine Prions in Peripheral Nerve Tissues

We recently reported the intraspecies transmission of L-type atypical bovine spongiform encephalopathy (BSE). To clarify the peripheral pathogenesis of L-type BSE, we studied prion distribution in nerve and lymphoid tissues obtained from experimentally challenged cattle. As with classical BSE prions, L-type BSE prions accumulated in central and peripheral nerve tissues.     

Enhancement of amyloid beta 42 secretion by 28 different presenilin 1 mutations of familial Alzheimer's disease.

Families bearing mutations in the presenilin 1 (PS1) gene develop early onset familial Alzheimer's disease (FAD). Further, some PS1 mutants enhance secretion of the longer form of amyloid beta protein (Abeta42). We constructed cDNAs encoding human PS1 harboring 28 FAD-linked mutations, and examined the effects of the expressed PS1 mutants on Abeta42 secretion in beta amyloid precursor producing COS-1 cells. All the mutants significantly enhanced the ratio of Abeta42 to total Abeta compared with wild-type PS1. However, the increase in Abeta42 ratio in cells with each PS1 mutation did not correlate with the reported age of onset of FAD caused by that mutation. These results suggest that increased Abeta42 secretion is important for the development of Alzheimer's disease (AD), but may not be the only factor contributing to the onset of AD.     

Evidence of [Ca(2+)]i elevation by anti-calreticulin immunoreactive protein in neurons

Calreticulin is a multifunctional Ca(2+)-binding protein. The effect of anti-calreticulin antibody on intracellular free calcium concentration [Ca(2+)]i was studied in cultured neurons using fura-2 based microfluorometry. Anti-calreticulin increased [Ca(2+)]i in a dose dependent manner. The anti-calreticulin antibody produced a rapid transient [Ca(2+)]i peak followed by a long slowly decaying plateau. Anti-calreticulin induced extracellular Ca(2+) influx in cultured neuron cells was blocked partially by N-methyl-D-aspartate receptor (NMDAR) antagonist 2-amino-5-phosphonovaleric acid (AP5) and spider polyamine toxin JSTX-3, which is recognized as a blocker of glutamatergic nervous system. Furthermore, anti-calreticulin induced intracellular Ca(2+) desensitized NMDAR. Dual immunofluorescent staining studies revealed that NMDAR co-localized with calreticulin in the cultured neurons. Thus, the signal transduction system of NMDA might be closely concerned with the extracellular calreticulin like protein.     

Pulmonary dirofilariasis: computed tomography findings and correlation with pathologic features

OBJECTIVE: The purpose of this study was to describe the computed tomography (CT) and pathologic features of 5 nodules of pulmonary dirofilariasis in 4 patients. METHODS: Four patients with 5 nodules of pathologically confirmed pulmonary dirofilariasis who under went CT were enrolled, and the imaging interpretations were retrospectively compared with the histopathologic characteristics. RESULTS: Three of the 4 patients had a solitary nodule, and the remaining patient had 2 nodules. All the nodules were distributed in the right lower lobe and were attached to the pleura. They were all round or oval in shape and ranged in size from 11 to 22 mm in largest diameter (mean=17 mm). On thinner section CT, the nodules had a well-defined smooth margin with or without a shallow notch; they were connected to the arterial branch and, occasionally, to the venous branch. On contrast-enhanced CT, all the nodules contained a homogeneous low-attenuation area, which corresponded to areas of coagulative necrosis on histopathologic examination. CONCLUSION: Although the CT findings of a pulmonary dirofilariasis nodule are nonspecific, awareness of the findings on contrast-enhanced CT and the pathologic appearance of this rare benign condition may facilitate its differentiation from a malignant nodule.     

Proposal of blood volume-corrected model for quantification of regional cerebral blood flow with H2 15O-PET and its application to AVF

Purpose It is generally assumed that vascular tracer activity is negligible in the quantification of regional cerebral blood flow (rCBF) with H₂¹⁵O and positron emission tomography (PET) under normal conditions. We attempted to surpass the assumption of abnormal vascular conditions where the vascular tracer activity is significant by introducing the vascular component into the model. Materials and methods H₂¹⁵O-dynamic and C¹⁵O PET scans were performed in an arteriovenous fistula (AVF) patient. Time–activity curves of regions of interest (ROIs) were analyzed with nonlinear least-square approximation to estimate the rCBF and fractional arterial blood volume (v_a) simultaneously with the proposed model and the standard model. Results The proposed model curve showed a fit to the time–activity curve of H₂¹⁵O at an ROI containing an enlarged vascular space induced by the AVF. The relation between the estimated v_a and CBV obtained with C¹⁵O-PET revealed that the ratio of v_a to CBV was approximately 0.23. The estimated rCBF with the proposed model in nonlesion ROIs corresponded to those of the standard model, with the estimated V_d 0.94 ml/ml. Conclusion The results supported the hypothesis that the blood volume-corrected model is applicable to the quantification of rCBF in a region with abnormal vascular structure. Furthermore, one of the advantages of the model is the feasibility of simultaneous estimation of the rCBF and arterial blood volume with dynamic-H₂¹⁵O PET scans.     

Self-expandable metallic stent placement for patients with inoperable esophageal carcinoma: investigation of the influence of prior radiotherapy and chemotherapy

Purpose The aim of this study was to evaluate the efficacy and complications of self-expandable metallic stent placement for patients with inoperable esophageal carcinoma after radiotherapy and/or chemotherapy. Materials and methods We obtained data from 19 patients with advanced or recurrent esophageal carcinoma between 1996 and 2000. In all patients, a self-expandable metallic stent was placed under fluoroscopic guidance. Dysphagia before and after stent placement was graded. Complications after stent placement were also evaluated. Data were compared between patients with and without prior radiotherapy and/or chemotherapy. Results The procedure was technically successful in all but one patient. The dysphagia grade improved in all patients. No life-threatening complications occurred. The other major complications such as mediastinitis occurred in two patients, and pneumonia and funnel phenomenon occurred in one patient each. These patients had a history of radiotherapy and/or chemotherapy prior to stent placement. Eight of the twelve patients with prior radiotherapy and/or chemotherapy compared with one of seven patients without prior therapy had persistent chest pain, which was a statistically significant difference (P < 0.05). Conclusion Placement of self-expandable metallic stents was effective for patients with advanced or recurrent esophageal carcinoma. However, prior irradiation and/or chemotherapy increased the risk of persistent chest pain after stent placement.     

Differences in vertebral,tibial, and iliac cancellous bone metabolism in ovariectomized rats

Bone histomorphometry is usually performed on the iliac bone in humans and the tibia or vertebrae in rats. Bone metabolism differences among skeletal sites may be problematic when translating experimental results from rats to humans, but data on such differences in rats are lacking. Therefore, we examined the differences in bone structure and metabolism among skeletal sites using the lumbar vertebra (LV), tibia, and iliac bone obtained from ovariectomized or sham-operated rats preoperatively and at various times from 3 days to 26 weeks postoperatively. The trabeculae were thicker in the LV, where bone metabolism was less active than at other sites, and numerous fine trabeculae were observed in the tibia, where bone metabolism was more active. The iliac bone structure and metabolism were intermediate between those of the tibia and LV. Ovariectomy induced lower bone volume and higher bone metabolism in all skeletal sites, but the changes were greatest and occurred earliest in the tibia, followed by the iliac bone and then LV. Ovariectomy caused changes in bone metabolic markers, which occurred earlier than those in bone tissue. Activation frequency (Ac.f) increased after ovariectomy. At week 26 in ovariectomized rats, Ac.f was highest in the tibia (3.13 N/year) but similar between iliac bone (0.87 N/year) and LV (1.39 N/year). Ac.f is reportedly 0.3–0.4 N/year in the iliac bone of postmenopausal women, suggesting that bone turnover in rats is several times higher than in humans. The reference values reported here are useful for translating experimental results from rats to humans.     

Guglielmi detachable coil embolization of cerebral aneurysms: 11 years' experience

OBJECT: The authors report on their 11 years' experience with embolization of cerebral aneurysms using Guglielmi Detachable Coil (GDC) technology and on the attendant anatomical and clinical outcomes. METHODS: Since December 1990, 818 patients harboring 916 aneurysms were treated with GDC embolization at University of California at Los Angeles Medical Center. For comparative purposes, the patients were divided into two groups: Group A included their initial 5 years' experience with 230 patients harboring 251 aneurysms and Group B included the later 6 years' experience with 588 patients harboring 665 aneurysms. Angiographically demonstrated complete occlusion was achieved in 55% of aneurysms and a neck remnant was displayed in 35.4% of lesions. Incomplete embolization was performed in 3.5% of aneurysms, and in 5% occlusion was attempted unsuccessfully. A comparison between the two groups revealed a higher complete embolization rate in patients in Group B compared with that in Group A patients (56.8 and 50.2%, respectively). The overall morbidity/mortality rate was 9.4%. Angiographic follow ups were obtained in 53.4% of cases of aneurysms, and recanalization was exhibited in 26.1% of aneurysms in Group A and 17.2% of those in Group B. The overall recanalization rate was 20.9%. Note that recanalization was related to the size of the dome and neck of the aneurysm. Overall incidence of delayed aneurysm rupture was 1.6%, a rate that improved in the past 5 years to 0.5%. Ten of 12 delayed ruptures occurred in large or giant aneurysms. CONCLUSIONS: The clinical and postembolization outcomes in patients treated with the GDC system have improved in the past 5 years. Aneurysm recanalization, however, is still a major limitation of current GDC therapy. Follow-up angiography is mandatory after GDC embolization of cerebral aneurysms. Further technical and device improvements are mandatory to overcome current GDC limitations.     

Three presenile patients in which neuropsychological and neuroimaging examinations suggest possible progression to dementia with Lewy bodies

We report three presenile patients who were initially suspected of having Alzheimer's disease (AD) or being in the prodromal stage of AD, regardless of visuoperceptual dysfunctions in daily living, because they lacked the core features and prodromal non‐motor symptoms of dementia with Lewy bodies. Subsequently, progression to dementia with Lewy bodies was suspected based on neuropsychological and neuroimaging findings; additionally, one of the three patients suffered from visual hallucinations. Neuropsychological examinations such as subjective contours, cube copying and block design in the Wechsler Adult Intelligence Scale‐III revealed visuoperceptual dysfunction in all three patients even when other cognitive functions were rather preserved. Brain magnetic resonance imaging revealed no significant brain atrophy, including in the parieto‐occipital area and the hippocampus, while brain ¹⁸F‐fluorodeoxyglucose positron emission tomography demonstrated right dominant metabolic reductions in the occipital lobe, including the primary visual cortex, in all three patients. We suggest the possibility of progression to dementia with Lewy bodies, but not AD or posterior cortical atrophy. Regardless of the presence of core features and prodromal non‐motor symptoms, this progression is suggested when there are difficulties only in higher‐level visual processing such as subjective contours and block design in the Wechsler Adult Intelligence Scale‐III, no significant atrophy of the parieto‐occipital area and hippocampus on brain magnetic resonance imaging, and hypometabolism in the occipital lobe including the primary visual cortex on brain ¹⁸F‐fluorodeoxyglucose positron emission tomography.