Association of apolipoprotein J-positive beta-amyloid plaques with dystrophic neurites in Alzheimer's disease brain

Apolipoprotein J (apoJ), also known as clusterin and SP-40,40, binds soluble beta-amyloid (Abeta and is up-regulated in the Alzheimer's disease (AD) brain. In the present study we classified apoJ-immunopositive Abeta deposits in AD temporal cortex, and found apoJ-immunoreactive plaques were often associated with dystrophic neurites. Quantitative immunohistochemical analysis of five AD brains showed that 29% of Abeta deposited in the parenchyma was associated with apoJ. Of Abeta deposits with apoJ immunopositivity, 71% were associated with phospho-tau-positive dystrophic neurites in the surrounding tissue. Conversely, 64% of phospho-tau-labeled neuritic deposits were labeled with apoJ. ApoJ was found at the core of these deposits, and co-localized with the amyloid staining agent thioflavine-S. To test the direct effects of apoJ on tau metabolism, we treated cells in culture with apoJ-containing conditioned media, and we injected apoJ-containing media into the rat hippocampus. Using both systems, we observed increases in levels of tau and phosphorylated tau. Our findings demonstrate that apoJ immunopositivity strongly correlates with the presence of amyloid and associated neuritic dystrophy in the neuropil of AD temporal cortex, and supports a model where extracellular apoJ facilitates the conversion of diffuse Abeta deposits into amyloid and enhances tau phosphorylation in neurites surrounding these of plaques.     

The usefulness of fractional anisotropy maps in localization of lacunar infarctions in striatum, internal capsule and thalamus

We aimed in this study to assess the clinical usefulness of fractional anisotropy (FA) maps in the evaluation of lacunar infarctions in striatum, internal capsule and thalamus. We retrospectively reviewed 28 patients (18 men, 10 women; mean age 63 years) who had acute lacunar infarction in striatum, internal capsule and thalamus on diffusion weighted MR imaging (DWI). Fractional anisotropy (FA) maps were generated in addition to conventional T2 weighted images (T2WI) and trace maps of DWI. Two radiologists reviewed the location of infarcts in combination with and without FA maps. Exact location of infarction was determined by FA maps, i.e. on the white band of internal capsule or outside the internal capsule. Accuracy and inter-observer agreement on determination of the location of infarction was evaluated. Accuracy of infarct localization by T2WI-DWI only was varied from 72 to 91% according to the observers. Inter-observer agreement value was moderate (Kappa=0.446), when images were interpreted by T2WI-DWI only. Clinical manifestation of each lesions were varied, but sensory motor stroke was mainly observed in thalamic lesion (50%), while pure motor hemiparesis was predominant in the case of infarct involving internal capsule, corona radiata (91%) and basal ganglia (83%). The FA map is useful in the evaluation of lacunar lesions in striatum, internal capsule and thalamus. Clinical presentation varies according to the exact location of lacunar infarctions, and more accurate diagnosis can be made by FA maps as well as conventional T2-weighted image and DWI.     

Three-dimensional venography of the brain with a volumetric interpolated sequence

Informed consent was obtained from all patients before participation; study was approved by institutional review board. Three-dimensional (3D) gradient-echo magnetic resonance sequences can be optimized for rapid acquisition through asymmetric k-space sampling and interpolation of image data. A T1-weighted volumetric interpolated brain examination sequence (acquisition time, 1 minute 24 seconds) was prospectively compared qualitatively and quantitatively with magnetization-prepared rapid acquisition gradient-echo sequence (acquisition time, 6 minutes 6 seconds) for venography of cerebral venous structures in 21 female and seven male consecutive patients (mean age, 52.9 years; range, 16-81 years). Although signal- and contrast-to-noise ratios were substantially lower for volumetric interpolated sequence, difference in the subjective quality of visualization of cerebral venous structures was not significant (P >.05). Volumetric interpolated brain examination seems promising as a more time-efficient alternative for 3D imaging of cerebral venous structures.     

Ureteroscopic lithotripsy under local anesthesia: analysis of the effectiveness and patient tolerability

OBJECTIVES: We tried to evaluate the feasibility and effectiveness of ureteroscopic lithotripsy under local anesthesia. METHODS: We evaluated the results of ureteroscopic lithotripsy under local anesthesia performed on 200 patients (male 91; female 109). We compared the pain perception during local ureteroscopic procedure to that of cystoscopy using a visual analogue pain scale recorded by the patient. RESULTS: The overall success rate was 93% (185/200). The success rates of the upper, mid and lower ureteral calculi were 83% (5/6), 78% (14/18), and 94% (166/176), respectively. The success rate was 94% (166/176) in calculi less than 10 mm, and 86% (30/35) in those more than 10 mm. There were 5 cases (3%) of complications: ureteral injury (1), pyelonephritis (2), and ureteral stricture (2). Although the mean pain scale score was higher in the ureteroscopy group (3.36+/-1.75) than in the cystoscopy group (3.13+/-1.92), the difference between the two groups was not statistically significant (p>0.05). Most of the patients tolerated pain during the procedure and only two patients required general anesthesia. Postoperative pain was also tolerable in most patients and only 8 (4%) patients required additional analgesics after the procedure. CONCLUSION: As the effectiveness and morbidity of ureteroscopic lithotripsy under local anesthesia are comparable to those of many other previous reports and as most of the patients could tolerate the pain of the procedure, we suggest that ureteroscopic lithotripsy can be performed effectively and safely under local anesthesia.     

Ischemic cardiomyopathy: value of different MRI techniques for prediction of functional recovery after revascularization

OBJECTIVE: The purpose of this study was to compare the value of different MRI techniques for the assessment of myocardial viability. SUBJECTS AND METHODS. Eighteen infarct patients (mean age +/- SD, 62 +/- 8 years) with myocardial ischemia were examined using MRI before and after revascularization. The MRI study before treatment consisted of an evaluation of first-pass perfusion, contractile function at rest and during dobutamine stress, and delayed hyperenhancement. Findings were correlated with segmental and global cardiac function after revascularization. RESULTS: In initially dysfunctional segments, the likelihood of functional recovery after revascularization was 91% for segments without delayed hyperenhancement, 43% for segments with delayed hyperenhancement with transmural extent of 75% or less, and 8% for segments with delayed hyperenhancement with transmural extent of more than 75% (p < 0.05). Improved function at dobutamine stress MRI indicated functional recovery in 87%, whereas functional recovery was observed in only 30% of segments not responding at dobutamine stress MRI (p < 0.05). No significant correlation was found between the results of first-pass perfusion MRI and functional recovery. The ejection fraction after revascularization was best predicted by the MRI-derived infarct volume (p < 0.001, R(2) = 0.63). CONCLUSION: A simple protocol consisting of baseline contractility and delayed enhancement MRI studies is adequate to differentiate dysfunctional but viable from nonviable myocardium. Dobutamine stress and perfusion MRI studies offer little or no additional information.     

Loss of Heterozygosity Analysis of Chromosome 17p13.1–13.3 and its Correlation with Clinical Outcome in Medulloblastomas

Cytogenetic and molecular genetic studies have shown that deletions on the short arm of chromosome 17 distal to p53 locus are the most common genetic events in medulloblastoma. We examined the occurrences and frequencies of allelic deletions on chromosome 17p13.1-13.3 by loss of heterozygosity (LOH) analysis to investigate the possible involvement of 17p13.1-13.3 in medulloblastoma development. We also performed survival analysis to determine whether LOH analysis of 17p13.1-13.3 can be used to predict prognosis in medulloblastoma. Loss of heterozygosity was analyzed by polymerase chain reaction on chromosome 17p13.1-13.3 using three microsatellite markers, TP53 on 17p13.1, D17S796 on 17p13.1-13.2, and D17S1574 on 17p13.3, in 17 medulloblastoma DNAs extracted either from archival tissue or fresh frozen tissue specimens. Allelic deletions were detected in five of 17 informative cases (29%) on TP53, eight of 17 informative cases (47%) on D17S796, and four of 17 informative cases (24%) on D17S1574. Overall, nine of 17 cases (53%) showed LOH on chromosome 17p13.1-13.3. The 5-year progression free survival (PFS) and 5-year overall survival rates were identical (59%). The 5-year PFS for nine medulloblastoma patients with LOH on 17p13.1-13.3 was 56%, and the 5-year PFS for eight medulloblastoma patients without LOH on 17p13.1-13.3 was 63%. In our survival analysis, we did not find a significant association between survival and LOH on 17p13.1-13.3. Our results support the notion that deletions of chromosome 17p13.1-13.3 may be involved in the pathogenesis of medulloblastoma. From survival analysis, we conclude that LOH on chromosome 17p13.1-13.3 may not be a significant predictor of prognosis in medulloblastoma.     

Effects of diabetes mellitus on astrocyte GFAP and glutamate transporters in the CNS

Diabetes mellitus increases the risk of central nervous system (CNS) disorders such as stroke, seizures, dementia, and cognitive impairment. The cellular mechanisms responsible for the increased risk of these disorders are incompletely understood. Astrocytes are proving critical for normal CNS function, and alterations in their activity could contribute to diabetes-related disturbances in the brain. We examined the effects of streptozotocin (STZ)-induced diabetes in rats on the level of the astrocyte intermediate filament protein, glial fibrillary acidic protein (GFAP), number of astrocytes, and levels of the astrocyte glutamate transporters, glutamate transporter-1 (GLT-1) and glutamate/aspartate transporter (GLAST), in the cerebral cortex, hippocampus, and cerebellum by Western blotting (WB) and immunohistochemistry (IH). Studies were carried out at 4 and 8 weeks of diabetes duration. Diabetes resulted in a significant decrease in GFAP protein levels (WB) in the hippocampus and cerebellum at 4 weeks and in the cerebral cortex, hippocampus and cerebellum by 8 weeks. Attenuated GFAP immunoreactivity (IH) was evident in the hippocampus, cerebellum and white matter regions such as the corpus callosum and external capsule at both 4 and 8 weeks of diabetes. Astrocyte cell counts of adjacent sections immunoreactive for S-100B were not different between control and diabetic animals. No significant differences were noted in astrocyte glutamate transporter levels in the cerebral cortex, hippocampus, or cerebellum at either time period (WB, IH). With the expanding list of astrocyte functions in the CNS, the role of astrocytes in diabetes-induced CNS disorders clearly warrants further investigation.     

Vestibular imbalance associated with a lesion in the nucleus prepositus hypoglossi area

BACKGROUND: The nucleus prepositus hypoglossi (NPH) is known to be a neural integrator of horizontal eye movements. Although the role of the human NPH is not well known, it may also function in postural balance, in view of its anatomic connections with the vestibular nuclei and vestibulocerebellum and of lesion studies in experimental animals. OBJECTIVE: To show that the human NPH contributes to vestibular function in addition to eye movement control. DESIGN: Case series. SETTING: University hospital.Patients Six patients with small and discrete brainstem infarctions that predominantly involved the NPH region.Main Outcome Measure Findings on magnetic resonance images. RESULTS: The NPH was affected at the lower pontine level in 2 patients and at the upper medullary level in 4. In addition to gaze-evoked nystagmus, all patients had vertigo, vomiting, and postural ataxia, suggesting vestibular dysfunction. The patients typically fell contralaterally or bilaterally to the lesion side. CONCLUSION: The NPH serves a vestibular function in addition to its oculomotor control function.     

Persistent increase of matrix metalloproteinases in cerebrospinal fluid of tuberculous meningitis

Matrix metalloproteinase (MMP)-2 and MMP-9 were analyzed by gelatin zymography and an enzyme-linked immunosorbent assay (ELISA) in a cerebrospinal fluid (CSF) from patients with tuberculous meningitis (n=24), acute aseptic meningitis (n=23) and the control (n=10). The MMP-2 and MMP-9 levels were significantly higher in the samples from the tuberculous meningitis patients than those from either the aseptic meningitis patients or the controls. In tuberculous meningitis, the patients with late neurologic complications had higher MMP-2 and MMP-9 levels than those without. The persistent increase in the MMP-2 and MMP-9 levels was associated with the development of complications following tuberculous meningitis. Inhibiting the MMPs may be an effective strategy for preventing or reducing the complications in tuberculous meningitis.     

Simple retrograde balloon dilation for treatment of ureteral strictures: etiology-based analysis

This study consists of an analysis of the results of simple retrograde balloon dilation in the treatment of ureteral strictures for the evaluation of the long-term efficacy of this procedure, and the factors affecting its success rate. A prospective study was performed on 43 ureteral strictures (22 malignant, 21 benign) from 37 patients treated with retrograde balloon dilation from October 1997 to May 1999. After the stricture segments were dilated, ureteral stents were indwelled uniformly for 3 weeks. Strictures were postoperatively followed up radiographically at 1, 3, 6 and 12 months, and annually thereafter. Success was defined by symptomatic and radiographic improvement. The follow-up periods ranged from 8 to 57 months (mean 41 months). The success rates of the benign strictures at 12 and 36 months were much higher than those of the malignant strictures (67 and 57% vs., 18 and 14%, p=0.0009). While 56% and 47% of the patients with strictures shorter than 2 cm were successful at 12 and 36 months, respectively, none with strictures longer than 2 cm were successful at the same follow-up periods (p=0.0002). Of the successful benign cases with a shorter segment at 12 months, 12 out of 14 (86%) showed persistent long-term successes at the 36 months follow-up. Other prognostic factors, such as sex, age, location, disappearance of a waist, dilation time and grade of hydronephrosis, were not found to influence the success rate. A multivariate analysis revealed the etiology and stricture length were the only significant prognostic factors affecting the final outcome (p=0.030 and p=0.0262, respectively, by Cox's proportional hazards model). In consideration of its minimal invasiveness and acceptable long-term outcome, simple retrograde balloon dilation is an effective treatment modality for benign ureteral stricture with a short segment (< or = 2 cm), and a shorter duration of stenting (3-weeks) is viable.