Voxel-based comparison of regional cerebral glucose metabolism between PSP and corticobasal degeneration

OBJECTIVES: Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are neurodegenerative disorders that may be accompanied by dementia and parkinsonism as clinical symptoms. The purpose of this study was to elucidate cerebral metabolic differences of these two diseases with cognitive impairments by [18F] fluorodeoxyglucose (FDG) and positron emission tomography (PET). METHODS: A total of 12 patients with PSP (age: 62.8+/-6.0 years old, m: 7, f: 5, Mini-Mental State Examination (MMSE): 23.4+/-2.6), 12 patients with CBD (age: 64.8+/-6.3 years old, m: 6, f: 6, MMSE: 22.9+/-4.5), and age-matched healthy subjects (normal control (NC)) (age: 63.8+/-7.7 years old, m: 7, f: 5) were subjected to FDG-PET to obtain glucose metabolic images. We compared regional cerebral metabolic images by a voxel-by-voxel analysis with statistical parametric mapping (SPM) among PSP, CBD, and NC subjects, and evaluated differences of hypometabolic regions. RESULTS: The patients with PSP showed reduced cerebral glucose metabolism in the medial and lateral frontal gyri, basal ganglia, and midbrain compared with NC, whereas the patients with CBD showed significant reduction in the parietal lobes (p<0.001). SPM also revealed parietal hypometabolism in CBD patients compared with PSP patients (p<0.001). CONCLUSIONS: The predominant parietal glucose metabolic reduction in CBD patients was different from previously reported findings. This finding would be the characteristic substance of patients with CBD accompanying cognitive impairments. Our findings suggest that measurement of glucose metabolism by PET and a voxel-based analysis is useful to understand the pathophysiology of these two diseases with cognitive impairments.     

Colocalization of CA19-9 and KL-6 to epithelial cells in dilated bronchioles in a patient with idiopathic pulmonary fibrosis complicated by diffuse alveolar damage

A 73-year-old woman with idiopathic pulmonary fibrosis (IPF) had an elevated serum CA19-9 level, but not KL-6. Her condition worsened and she subsequently died and this was associated with a rise in the serum KL-6 level. At autopsy, the lung showed a honeycomb appearance macroscopically and, microscopically, hyaline membrane formation was seen. Immunohistochemical staining revealed partial colocalization of KL-6 and CA19-9 to dilated bronchiolar cells. These features suggest that the mechanisms that cause the synthesis and release of CA19-9 and KL-6 from damaged lung tissue in IPF are likely to differ from those in diffuse alveolar damage. In addition, serum KL-6 levels may reflect the severity of disease more sensitively than CA19-9 levels.     

Increased clusterin (apolipoprotein J) expression in human and mouse brains infected with transmissible spongiform encephalopathies

Clusterin (apolipoprotein J), a multifunctional protein involved in amyloidogenesis in Alzheimer's disease, was studied immunohistochemically in both human transmissible spongiform encephalopathies (TSEs) and a mouse model of human TSE. Clusterin immunoreactivity was co-localized with plaque-type deposits but not with punctate-type prion protein (PrP) deposits in human TSEs. On the other hand, clusterin-positive astrocytes were readily demonstrated in the regions of punctate PrP deposits, but not around plaque PrP deposits despite the presence of surrounding astrocytes. Clusterin expression in astrocytes was not disease specific, but the punctate immunoreactivity for clusterin was more prominently demonstrated in TSEs with punctate PrP deposits. Serial analysis in the mouse model of human TSE revealed that clusterin expression in astrocytes was enhanced in the lesions with punctate-type PrP deposits during the disease progression. Thus, the induction of clusterin expression in astrocytes could be more enhanced by punctate-type PrP deposits than by plaque-type deposits. The clusterin molecules co-localized in plaque PrP deposits might be derived not from surrounding astrocytes but from other resources such as cerebrospinal fluid and blood plasma, both of which contain clusterin in significant amounts. Taken together with previously reported findings of the anti-amyloidogenic property in clusterin, our findings suggest that clusterin may be induced as one of the important molecules participating in the neurodegeneration caused by abnormally deposited PrP.     

Combined Analysis of CSF Tau Levels and [(123)I]Iodoamphetamine SPECT in Mild Cognitive Impairment: Implications for a Novel Predictor of Alzheimer's Disease

OBJECTIVE: The aim of this study was to establish an objective and reliable index to predict the development of Alzheimer's disease in a large pool of elderly patients with mild cognitive impairment. METHOD: Twenty-three patients with probable Alzheimer's disease, 22 patients with mild cognitive impairment who eventually developed Alzheimer's disease, eight patients with mild cognitive impairment who did not develop dementia, and 19 cognitively normal subjects were included in the study. The authors constructed a new diagnostic index, the CSF-CBF index, based on CSF tau levels divided by regional cerebral blood flow (CBF) in the posterior cingulate cortex. RESULTS: Receiver operating characteristic analysis showed that applying a cutoff value for the CSF-CBF index of 296.0 achieved a sensitivity of 88.5% and a specificity of 90.0% in discriminating mild cognitive impairment that progressed to Alzheimer's disease from mild cognitive impairment that did not progress to Alzheimer's disease. CONCLUSIONS: The CSF-CBF index is useful in predicting Alzheimer's disease in subjects with mild cognitive impairment.     

Platelet reactivity in spontaneously diabetic rats is independent from blood glucose and insulin levels

Diabetes is associated with thrombotic disorders. Chemically induced and spontaneously induced diabetic animals and various in vitro tests have been used to reveal the prothrombotic state of diabetic patients. However, the results are not consistent. In the present study, platelet reactivity of spontaneously diabetic Goto-Kakizaki rats in vivo and in vitro was evaluated by laser-induced and shear-induced thrombosis models, which are physiologically relevant to thrombosis. Both results showed platelet hyperreactivity.     

Is the gastric epithelial barrier regulated by cadherin recruitment?

While still highly controversial, regulation of junctional structure remains an important feature in many physiological/pathological conditions. Mizuno et al. here report a mechanism in stomach epithelia where additional copies of cadherins appear to be recruited to the cell surface, apparently to maintain the solute barrier. This phenomenon may represent an important novel mechanism which epithelia may use to enhance barrier.     

Autosomal dominant precocious osteoarthropathy due to a mutation of the cartilage oligomeric matrix protein (<Emphasis Type="Italic">COMP</Emphasis>) gene: further expansion of the phenotypic variations of <Emphasis Type="Italic">COMP</Emphasis> defects

We report on a Japanese family of four generations with an autosomal dominant precocious osteoarthropathy. The cardinal clinical manifestations of affected individuals were painful weight-bearing large joints, which started in late childhood or adolescence. The radiological hallmarks included coxa plana, mild epiphyseal dysplasia of the knee, and round talar domes with tibiotalar slant in childhood, which evolved into degenerative joint diseases in adulthood. The disease phenotype was cosegregated with a mutation of the cartilage oligomeric matrix protein (COMP) gene in the family members, who underwent molecular evaluation. COMP mutations have been reported in a mild form of multiple epiphyseal dysplasia (MED), Ribbing type, as well as allied disorders with more severe manifestations, such as MED Fairbank type and pseudoachondroplasia. Unlike previously reported cases with the Ribbing type, the present patients did not have short stature or brachydactyly. This report expands further the phenotypic variations of COMP defects.