Kazunari Ishii

High Signal Intensity in the Dentate Nucleus and Globus Pallidus on Unenhanced T1-weighted MR Images: Relationship with Increasing Cumulative Dose of a Gadolinium-based Contrast Material

PURPOSE To explore any correlation between the number of previous gadolinium-based contrast material administrations and high signal intensity (SI) in the dentate nucleus and globus pallidus on unenhanced T1-weighted magnetic resonance (MR) images. MATERIALS AND METHODS The institutional review board approved this study, waiving the requirement to obtain written informed consent. A group of 381 consecutive patients who had undergone brain MR imaging was identified for cross-sectional analysis. For longitudinal analysis, 19 patients who had undergone at least six contrast-enhanced examinations were compared with 16 patients who had undergone at least six unenhanced examinations. The mean SIs of the dentate nucleus, pons, globus pallidus, and thalamus were measured on unenhanced T1-weighted images. The dentate nucleus-to-pons SI ratio was calculated by dividing the SI in the dentate nucleus by that in the pons, and the globus pallidus-to-thalamus SI ratio was calculated by dividing the SI in the globus pallidus by that in the thalamus. Stepwise regression analysis was undertaken in the consecutive patient group to detect any relationship between the dentate nucleus-to-pons or globus pallidus-to-thalamus SI ratio and previous gadolinium-based contrast material administration or other factors. A random coefficient model was used to evaluate for longitudinal analysis. RESULTS The dentate nucleus-to-pons SI ratio showed a significant correlation with the number of previous gadolinium-based contrast material administrations (P < .001; regression coefficient, 0.010; 95% confidence interval [CI]: 0.009, 0.011; standardized regression coefficient, 0.695). The globus pallidus-to-thalamus SI ratio showed a significant correlation with the number of previous gadolinium-based contrast material administrations (P < .001; regression coefficient, 0.004; 95% CI: 0.002, 0.006; standardized regression coefficient, 0.288), radiation therapy (P = .009; regression coefficient, -0.014; 95% CI: -0.025, -0.004; standardized regression coefficient, -0.151), and liver function (P = .031; regression coefficient, 0.023; 95% CI: 0.002, 0.044; standardized regression coefficient, 0.107). The dentate nucleus-to-pons and globus pallidus-to-thalamus SI ratios in patients who had undergone contrast-enhanced examinations were significantly greater than those of patients who had undergone unenhanced examinations (P < .001 for both). CONCLUSION High SI in the dentate nucleus and globus pallidus on unenhanced T1-weighted images may be a consequence of the number of previous gadolinium-based contrast material administrations.

Regional cerebral glucose metabolism in dementia with Lewy bodies and Alzheimer's disease

Objective: To delineate the features of regional cerebral metabolic rate of glucose(CMRglc) in dementia with Lewy bodies (DLB). Methods: We compared absolute CMRglc in 12 patients with a clinical diagnosis of DLB, 12 patients with a clinical diagnosis of Alzheimers disease (AD), and 12 normal volunteers (NC), using 18F-fluorodeoxyglucose (FDG) and PET. The three groups were matched for age and sex, and there were no differences in disease duration or severity of cognitive disturbances between the DLB and AD groups. Results: CMRglc was significantly lower in patients with DLB than in that of NC in most parts of the brain, except the sensorimotor cortices, basal ganglia, thalamus, and pons. Between the DLB and AD groups, there were significant regional CMRglc differences in the medial and lateral occipital lobes. In DLB and AD, the CMRglc reduction patterns were similar, though the global metabolic reduction was larger in DLB, and the occipital CMRglc reduction in DLB could differentiate DLB from AD. The relative occipital CMRglc(normalized to the sensorimotor CMRglc) was a useful measure for the differential diagnosis of DLB from AD. The sensitivity and the specificity were 92% when using the minimal value of the normalized occipital CMRglc in the NC group as the cut-off point. Conclusion: These different regional CMRglc reductions substantiate the pathologic, neurochemical, and clinical differences between DLB and AD.

WSX-1 Is Required for Resistance to Trypanosoma cruzi Infection by Regulation of Proinflammatory Cytokine Production

WSX-1 is a class I cytokine receptor with homology to the IL-12 receptors and is essential for resistance to Leishmania major infection. In the present study, we demonstrated that WSX-1 was also required for resistance to Trypanosoma cruzi. WSX-1-/- mice exhibited prolonged parasitemia, severe liver injury, and increased mortality over wild-type mice. WSX-1-/- splenocytes produced enhanced levels of Th2 cytokines, which were responsible for the prolonged parasitemia. Massive necroinflammatory lesions were observed in the liver of infected WSX-1-/- mice, and IFN-gamma that was overproduced in WSX-1-/- mice compared with wild-type mice was responsible for the lesions. In addition, vast amounts of various proinflammatory cytokines, including IL-6 and TNF-alpha, were produced by liver mononuclear cells in WSX-1-/- mice. Thus, during T. cruzi infection, WSX-1 suppresses liver injury by regulating production of proinflammatory cytokines, while controlling parasitemia by suppression of Th2 responses, demonstrating its novel role as an inhibitory regulator of cytokine production.

Regional cerebral blood flow difference between dementia with Lewy bodies and AD

Article abstract The authors studied 14 patients with dementia with Lewy bodies (DLB), 14 patients with AD, and 14 healthy control subjects with N-isopropyl-p-[123I]iodoamphetamine SPECT. Comparison with the statistical parametric mappings revealed that relative cerebral blood flow was lower in the occipital lobes and higher in the right medial temporal lobe in the DLB group than in the AD group. Decreased occipital perfusion and relatively well preserved medial temporal perfusion are features that distinguish DLB from AD.

Frontal lobe hypometabolism and depression in Alzheimer's disease

Depression is common in Alzheimers disease (AD). Clinicoanatomic studies in focal brain injuries and functional imaging studies both in primary depression and in depression secondary to neurologic diseases have demonstrated involvement of the frontal lobe. Frontal involvement has not been established in the depression of AD. We studied the correlation between focal brain metabolic abnormalities and depression in AD. In 53 patients with probable AD of minimal to moderate disability, we assessed the severity of depression using the Neuropsychiatric Inventory and correlated the depression score with regional cerebral glucose metabolism determined by 18F-fluorodeoxyglucose and PET. Depression was present in 19 patients (36%). The depression score correlated significantly with normalized glucose metabolic rates in the bilateral superior frontal and left anterior cingulate cortices. These results indicated an association between depression and decreased activity in the frontal lobe in AD and support frontal involvement, especially in the left side, in depression, irrespective of disease etiology.

Estimation of liver function using T1 mapping on Gd-EOB-DTPA-enhanced magnetic resonance imaging.

Objectives:To investigate the ability of T1 mapping of liver on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging for the estimation of liver function. Materials and Methods:Local institutional review board approved this study. Ninety-one patients (64 men, 27 women; mean age, 67.4 years) were classified into 4 groups as follows: normal liver function (NLF), n = 16; chronic hepatitis (CH), n = 38; liver cirrhosis with Child-Pugh A (LCA), n = 20; and liver cirrhosis with Child-Pugh B (LCB), n = 17. Look-Locker sequences (single slice multiphase imaging using gradient-echo sequence with inversion recovery pulse) were obtained before and at 3, 8, 13, and 18 minutes after Gd-EOB-DTPA administration. T1 mapping of liver parenchyma was calculated from the Look-Locker sequence. T1 relaxation time of liver and reduction rate of T1 relaxation time between pre- and postcontrast enhancement were measured. The Bonferroni t test was used for comparisons between the 4 groups. Results:Precontrast T1 relaxation times were significantly longer for LCA and LCB than for NLF, and that of LCB was longer than that of chronic hepatitis (P < 0.05). Postcontrast T1 relaxation times were significantly longer for LCB than for other groups at all time points. Those of LCA were longer than those of NLF at all time points. Reduction rates were significantly lower for LCB than for the other groups at ≥8 minutes. Conclusions:Evaluation of hepatic uptake of Gd-EOB-DTPA using T1 mapping of liver parenchyma can help estimate liver function.

Differences in cerebral metabolic impairment between early and late onset types of Alzheimer's disease.

UNLABELLED The purpose of this study was to delineate the specific patterns of cerebral glucose metabolism with regard to the time of onset of Alzheimers disease (AD). METHODS Two groups of 20 AD patients with different ages of onset were examined. The early onset (EO) and late onset (LO) groups had mean ages of onset of 53.9 and 72.7 years. Groups of age-matched normal subjects were used as controls. A regional relative cerebral glucose metabolic image of each subject was obtained by 2-[18F] fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). NEUROSTAT program was used for spatial normalization and voxel-based statistical parametric mapping (SPM) 99 was used for statistical analyses. RESULTS Both AD groups had significant hypometabolic regions in the bilateral parieto-temporal regions compared with the age-matched groups. The EO group had more severe hypometabolism in the bilateral parietal and posterior cingulate cortices and precuneus region than the LO group. However, LO group showed no significant hypometabolic regions compared to the EO group. CONCLUSION The effects of time of AD onset were delineated as a double dissociation, that is, EO AD patients have a more severe reduction of glucose metabolism. Our finding suggests the existence of biological subtypes of AD.

Visual hallucinations and regional cerebral metabolism in dementia with lewy bodies (DLB)

To investigate the neurobiological bases of visual hallucinations in dementia with Lewy bodies (DLB), regional cerebral glucose metabolism was compared among three patient groups; DLB with visual hallucinations, DLB without visual hallucinations and Alzheimers disease (AD) without visual hallucinations. The regional metabolism was significantly lower in both DLB groups than in the AD group in the primary visual area and the posterior temporal, parietal and lateral occipital association areas. The hypometabolism in the right posterior temporal and parietal areas was significantly milder in DLB with visual hallucinations than in DLB without hallucinations. The hypometabolism in the primary visual cortex and the relatively preserved metabolism in the right temporoparietal association cortices may be associated with the occurrence of visual hallucinations in DLB patients.

Function of sigma1 receptors in Parkinson's disease

Objective –  The objective of this study was to investigate the mapping of sigma1 receptors in Parkinsons disease (PD) using [11C]SA4503 and positron emission tomography (PET), and to assess whether sigma1 receptors are involved in the damaged dopaminergic system in PD patients.

Nippocystatin, a cysteine protease inhibitor from Nippostrongylus brasiliensis, inhibits antigen processing and modulates antigen-specific immune response.

ABSTRACT During infection, parasites evade the host immune system by modulating or exploiting the immune system; e.g., they suppress expression of major histocompatibility complex class II molecules or secrete cytokine-like molecules. However, it is not clear whether helminths disturb the immune responses of their hosts by controlling the antigen-processing pathways of the hosts. In this study, we identified a new cysteine protease inhibitor, nippocystatin, derived from excretory-secretory (ES) products of an intestinal nematode,Nippostrongylus brasiliensis. Nippocystatin, which belongs to cystatin family 2, consists of 144 amino acids and is secreted as a 14-kDa mature form. In vivo treatment of ovalbumin (OVA)-immunized mice with recombinant nippocystatin (rNbCys) profoundly suppressed OVA-specific proliferation of splenocytes but not non-antigen-specific proliferation of splenocytes. OVA-specific cytokine production was also greatly suppressed in rNbCys-treated mice. Although the serum levels of both OVA-specific immunoglobulin G1 (IgG1) and IgG2a were not affected by rNbCys treatment, OVA-specific IgE was preferentially downregulated in rNbCys-treated mice. In vitro rNbCys inhibited processing of OVA by lysosomal cysteine proteases from the spleens of mice. Mice with anti-nippocystatin antibodies became partially resistant to infection with N. brasiliensis. Based on these findings, N. brasiliensis appears to skillfully evade host immune systems by secreting nippocystatin, which modulates antigen processing in antigen-presenting cells of hosts.