CD3+ B-1a Cells as a Mediator of Disease Progression in Autoimmune-Prone Mice.

B-1a cells are distinguishable from conventional B cells, which are designated B-2 cells, on the basis of their developmental origin, surface marker expression, and functions. In addition to the unique expression of the CD5 antigen, B-1a cells are characterized by the expression level of CD23. Although B-1a cells are considered to be independent of T cells and produce natural autoantibodies that induce the clinical manifestations of autoimmune diseases, there is much debate on the role of B-1a cells in the development of autoimmune diseases. We examined the involvement of B-1a cells in autoimmune-prone mice with the lpr gene. MRL/lpr and B6/lpr mice exhibited lupus and lymphoproliferative syndromes because of the massive accumulation of CD3+CD4-CD8-B220+ T cells. Interestingly, the B220+CD23-CD5+ (B-1a) cell population in the peripheral blood and peritoneal cavity increased with age and disease progression. Ninety percent of B-1a cells were CD3 positive (CD3+ B-1a cells) and did not produce tumor necrosis factor alpha, interferon gamma, or interleukin-10. To test the possible involvement of CD3+ B-1a cells in autoimmune disease, we tried to eliminate the peripheral cells by hypotonic shock through repeated intraperitoneal injections of distilled water. The fraction of peritoneal CD3+ B-1a cells decreased, and symptoms of the autoimmune disease were much milder in the distilled water-treated MRL/lpr mice. These results suggest that CD3+ B-1a cells could be mediators of disease progression in autoimmune-prone mice.

An investigation of asymmetric reduction in dopamine transporter density in patients with Parkinson's disease.

Asymmetric motor symptoms and the contralateral side of dopaminergic deficits are commonly observed in patients with Parkinson's disease. The laterality of the specific binding ratio (SBR) for dopamine transporter single-photon emission computed tomography may be useful for estimation of reduced dopamine transporter density in striatum of patients with Parkinson's disease. SBR with Southampton method (S-SBR) is widely used to evaluate in our country, but the results occasionally contradict with that of motor symptoms or visual evaluation in clinical practice, thus preventing a confident diagnosis. We reported dopamine transporter evaluation with distance-weighted histogram (DWH). We hypothesized that the SBR calculated using DWH (DWH-SBR) may also be useful to evaluate the laterality. The purpose of this study was to investigate the laterality of the SBR versus the asymmetry of motor symptoms, and versus visual evaluation. In total, 100 adult patients with Parkinson's disease were enrolled in our study. The symptom-affected side, the visual-affected side, and the lower SBR side were evaluated. The evaluation was performed in a blinded manner. Correlations between the Hoehn and Yahr scale (HY scale) and both the SBRs were also investigated. Concordance of lower DWH-SBR side for visual-affected side was significantly higher (99.0%) than it of lower S-SBR side (86.0%, P < 0.01). The HY scale was significantly related to both lower S-SBR and DWH-SBR (P < 0.01). The DWH method might minimize the disagreement of laterality between the SBR and visual evaluation, and be useful for making a confident diagnosis in patients with Parkinson's disease.

Optimization of the uptake method for estimating renal clearance of 99mTc mercaptoacetyltriglycine.

OBJECTIVE: To improve the estimation of 99mTc mercaptoacetyltriglycine clearance in the renal uptake method by optimizing the conditions of renal depth, background, threshold for renal boundary determination, and time interval for integrating renal counts. METHODS: Dynamic renal imaging was performed in 232 patients with dual energy window acquisition (main, 140 +/- 14keV; sub, 122.5 3.5keV). For drawing renal regions of interest (ROIs), cut-off methods with 50% and 70% of the highest renal pixel counts were used. For drawing the backgrounds, circumferential and lateral-inferior quadrant peri-renal ROIs were used. For setting the time interval, periods of 1-2, 1-2.5, 1.5-2.5, 1.5-3 and 2-3 min post-injection were used. For determining renal depth, three methods of a theoretical exponential function using scatter fraction, Tønnesen's formula, and linear combination of scatter fraction and Tønnesen's formula were used. The scatter fraction was calculated using the counts in renal ROIs in the two energy windows. Using every combination of these conditions, renal uptake was calculated. As a reference, one-sample clearance was calculated from a blood sample taken at 30 min post-injection following Bubeck's formula. According to the methods for estimating renal depth, three non-linear regression models were derived to convert renal uptake to clearance. Using one-sample clearance and integrated renal counts as dependent and independent variables, data were fitted to the models to determine the necessary constants. The correlations between the model estimated clearances and one-sample clearance were investigated. RESULTS: One-sample clearance ranged from 11 to 404 ml x min(-1) per 1.73 m2. More than half of the regression using renal depth determined by the scatter fraction alone failed to converge. Among the successfully converged regressions, all model estimated clearances showed significant correlations (P<0.01) with one-sample clearance. The best correlation was observed in the model using renal depth determined by the combination of scatter fraction and Tønnesen's formulas, renal ROIs by 50% cut-off, lateral-inferior background and time interval of 2-3 min (r=0.898, P<0.001). CONCLUSION: The renal uptake method for estimating the clearance of mercaptoacetyltriglycine can be improved by the processing conditions proposed here.

Improved accuracy in estimation of left ventricular function parameters from QGS software with Tc-99m tetrofosmin gated-SPECT: a multivariate analysis.

UNLABELLED: The purpose of this study was to verify whether the accuracy of left ventricular parameters related to left ventricular function from gated-SPECT improved or not, using multivariate analysis. METHODS: Ninety-six patients with cardiovascular diseases were studied. Gated-SPECT with the QGS software and left ventriculography (LVG) were performed to obtain left ventricular ejection fraction (LVEF), end-diastolic volume (EDV) and end-systolic volume (ESV). Then, multivariate analyses were performed to determine empirical formulas for predicting these parameters. The calculated values of left ventricular parameters were compared with those obtained directly from the QGS software and LVG. RESULTS: Multivariate analyses were able to improve accuracy in estimation of LVEF, EDV and ESV. Statistically significant improvement was seen in LVEF (from r = 0.6965 to r = 0.8093, p < 0.05). Although not statistically significant, improvements in correlation coefficients were seen in EDV (from r = 0.7199 to r = 0.7595, p = 0.2750) and ESV (from r = 0.5694 to r = 0.5871, p = 0.4281). CONCLUSION: The empirical equations with multivariate analysis improved the accuracy in estimating LVEF from gated-SPECT with the QGS software.

Correct localization of epileptogenic focus with I-123 iomazenil cerebral benzodiazepine receptor imaging: a case report of temporal lobe epilepsy with discordant ictal cerebral blood flow SPECT.

A 26-year-old female with intractable epileptic seizures was studied with I-123 iomazenil cerebral benzodiazepine receptor, I-123 IMP inter-ictal and Tc-99m ECD ictal cerebral blood flow SPECT. The ictal cerebral blood flow SPECT indicated the location of the seizures to be in the left temporal lobe, where increased regional cerebral blood flow was noted in marked contrast to the inter-ictal SPECT. Ictal electroencephalograms (EEGs) recorded with scalp and sphenoidal electrodes also suggested the left temporal lobe as the location of the seizures. On I-123 iomazenil SPECT, however, decreased benzodiazepine receptor density was demonstrated in the right temporal lobe. MRI showed mild atrophy and abnormal signal intensity in the right temporal lobe. Ictal EEGs recorded with intracranial electrodes revealed that abnormal electrical activity of the brain always emerged from the right temporal lobe and then propagated to the contralateral side. Based on the findings of intracranial EEGs, partial resection of the right anterior temporal lobe including hippocampus was performed. After the surgery, no seizure occurred. Pathological examination of the surgical specimens revealed hippocampal sclerosis. This case suggested that cerebral benzodiazepine receptor imaging with I-123 iomazenil can be helpful for correct localization of epileptogenic foci.

Comparison of myocardial fatty acid metabolism with left ventricular function and perfusion in cardiomyopathies: by 123I-BMIPP SPECT and 99mTc-tetrofosmin electrocardiographically gated SPECT.

OBJECTIVE: To investigate myocardial fatty acid metabolism and its relationship with left ventricular (LV) function and perfusion in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). METHODS: Thirty-nine patients with cardiomyopathies (58 +/- 14 y), comprising 15 DCM and 24 HCM, and 9 age-matched healthy controls were studied with 123I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and 99mTc-tetrofosmin (TF) electrocardiographically gated SPECT. As parameters of myocardial fatty acid metabolism, the heart-to-mediastinum ratio (H/M) and global washout of BMIPP were calculated from early and delayed planar images, while regional BMIPP uptake and washout were calculated from SPECT. In TF study, the H/M (H/M-TF) and LV ejection fraction (LVEF) were calculated as global parameters of perfusion and function, while regional TF uptake and wall thickening index were calculated as regional parameters of perfusion and function using the Quantitative Gated SPECT software. The differences in the parameters and the correlations between the parameters from the 2 studies were investigated by one-way ANOVA and multiple linear regression analysis. RESULTS: BMIPP uptake was decreased (p < 0.05), and its washout was increased (p < 0.05) in DCM and HCM. In multiple linear regression analysis, global BMIPP parameters showed no significant correlation with LVEF (p > 0.05), but showed a significant correlation with H/M-TF (p < 0.05) in DCM and HCM. According to the partial correlation coefficient, early H/M was the only significant factor (p < 0.05) for predicting H/M-TF in DCM and HCM. Multiple linear regression analysis on regional parameters showed regional BMIPP parameters had no correlation with regional function (p > 0.05) but had a significant correlation with regional perfusion (p < 0.0001) in DCM. In HCM, regional BMIPP parameters showed significant multiple linear correlations with both regional function (p < 0.005) and perfusion (p < 0.0001). According to the partial correlation coefficients, delayed regional BMIPP uptake was the most significant factor for predicting regional function in HCM, while early regional BMIPP uptake was the only or the most significant factor for predicting regional perfusion in DCM and HCM, respectively. CONCLUSION: In DCM, BMIPP uptake and washout could not reflect LV function. In HCM, regional delayed BMIPP uptake might be useful for evaluating regional function. In DCM and HCM, early BMIPP uptake might be largely determined by myocardial perfusion.

Moderately T2-weighted images obtained with the single-shot fast spin-echo technique: differentiating between malignant and benign urinary obstructions.

The purpose of this study was to determine whether a distinction could be made between benign and malignant urinary obstructions in moderately T(2)-weighted images obtained with the single-shot fast spin-echo technique. Forty-four lesions in 39 patients with urinary obstruction were evaluated with the single-shot fast spin-echo (SSFSE) technique with an effective TE of 90-100 ms and without fat saturation. Benign and malignant lesions were compared for the presence of ureteral wall thickening and a signal intensity relative to the proximal ureteral wall. Statistically significant differences were found between benign and malignant lesions in both morphologic change (P<0.0001) and signal intensity of the lesions at the obstruction position (P<0.0001). The combination of wall thickening and increased signal intensity as a predictor of malignant disease yielded a sensitivity of 88% and a specificity of 100%. Neither increased signal intensity nor wall thickening as a predictor of benign disease yielded a sensitivity of 89% and a specificity of 88%. The moderately T(2)-weighted SSFSE technique without fat saturation can accurately distinguish between benign and malignant urinary obstructions.

Impaired cardiac sympathetic nerve function in patients with Kawasaki disease: comparison with myocardial perfusion.

Kawasaki disease (KD) is a leading cause of CAD in children. The impairment of cardiac sympathetic nerve function (CSNF) in the adult patients with coronary artery disease (CAD) could often be seen. However, little is known concerning the impairment of CSNF in KD patients. We investigated CSNF and its relationship with myocardial perfusion in KD patients. Eleven children with KD and 4 controls were studied with 123I-metaiodobenzylguanidine (MIBG) and stressed 201Tl single photon emission computed tomography. By the findings on coronary artery angiography (CAG), the patients were divided into 2 groups: A, without stenosis; B, with significant stenosis and/or old myocardial infarction. CSNF was evaluated from the uptake of 123I-MIBG. While myocardial perfusion was evaluated from 201Tl uptake. The numbers of patients in the groups A and B were 7 and 4. Perfusion defect was found in 0, and 2 patients in group A (0%), and B (50%). 123I-MIBG defects were found in 1 and 4 patients in the group A (14%) and B (100%). There were excellent concordances between the finding of 201Tl and 123I-MIBG in group A. While in group B, the coronary territories with 123I-MIBG defects were significantly more than those with perfusion defects (p < 0.05). In KD patients, the impairment of CSNF might be subsequent to coronary artery stenosis and was more severe than the injury of myocardial perfusion.

Low-field-strength MR imaging of failed hip arthroplasty: association of femoral periprosthetic signal intensity with radiographic, surgical, and pathologic findings.

PURPOSE: To investigate the association between periprosthetic signal intensity at low-field-strength magnetic resonance (MR) imaging after failed hip arthroplasty and radiographic, surgical, and pathologic findings. MATERIALS AND METHODS: The study group comprised 22 consecutive women who underwent hip arthroplasty (mean age, 62 years; age range, 35-74 years). All patients underwent MR imaging prior to revision surgery. Coronal fast short inversion time inversion-recovery (STIR) images and spin-echo T1-weighted images were obtained with a 0.5-T MR imaging unit before and after administration of contrast material. The periprosthetic region was divided into the seven femoral Gruen zones. Two observers retrospectively analyzed signal intensity patterns. Association of signal intensity patterns with radiographic, surgical, and pathologic findings was determined with chi2 analysis and generalized estimating equations. RESULTS: Diagnostic-quality images were obtained for 150 zones. Periprosthetic signal intensity was greater than that of bone marrow in the distal femur on the fast STIR images, and no contrast enhancement was seen on the T1-weighted images (type I signal intensity pattern) in 11 zones. Signal intensity was greater than that of bone marrow on the fast STIR images, and contrast enhancement was seen on the T1-weighted images (type II signal intensity pattern) in 45 zones. Signal intensity was less than or equal to that of bone marrow on the fast STIR images, and no contrast enhancement was seen on the T1-weighted images (type III signal intensity pattern) in 94 zones. Type I and II patterns were associated with focal or nonfocal lucency, an unstable stem, and fibrosis or granuloma. A type III pattern was associated with a normal radiographic appearance, a stable stem, and normal bone tissue. Significant association was demonstrated between periprosthetic signal intensity and radiographic (P <.001, chi2 test and generalized estimating equations), surgical (P <.05, Mantel-Haenszel chi2 test and generalized estimating equations), and pathologic findings (P <.05, chi2 test). CONCLUSION: Low-field-strength MR imaging depicted periprosthetic tissue signal intensity that was significantly associated with radiographic, surgical, and pathologic findings.

[Imaging findings of pulmonary vascular disorders in portal hypertension].

PURPOSE: The purpose of this study was to demonstrate and compare the imaging findings of hepatopulmonary syndrome and portopulmonary hypertension. MATERIALS AND METHODS: We retrospectively reviewed the imaging findings of five patients with hepatopulmonary syndrome and four patients with portopulmonary hypertension. We evaluated chest radiographs, chest and abdominal computed tomography (CT) scans, 99mTc-macroaggregated albumin (MAA) lung perfusion scans, and pulmonary angiograms. RESULTS: In patients with hepatopulmonary syndrome, the presence of peripheral pulmonary vascular dilatation was detected by chest radiograph, chest CT scan, and pulmonary angiogram, especially the basilar segment. 99mTc-MAA lung perfusion scan showed extrapulmonary tracer distribution (brain, thyroid, and kidney), which revealed pulmonary R-L shunting. In patients with portopulmonary hypertension, chest radiographs and chest CT scans showed the classic findings of primary pulmonary hypertension. In patients with both disorders, extrahepatic features of portal hypertension including ascites, splenomegaly, and portosystemic collateral vessels were seen on abdominal CT. CONCLUSION: In conclusion, chest radiographs and CT in hepatopulmonary syndrome usually showed peripheral pulmonary vascular dilatation, whereas those in portopulmonary hypertension showed central pulmonary artery dilatation. The extrahepatic features of portal hypertension might be helpful for the diagnosis of both disorders.

[Evaluation of ultra-low-dose thoracic multi-detector-row CT using different reconstruction kernels and new reconstruction algorithms].

CT has great advantages in detecting early-stage small lung cancer and is becoming common in lung cancer screening. Multi-detector-row CT (MDCT) can provide thin-slice images with low radiation exposure. In this study, ultra-low-dose (5 mAs: 10 mAs, 0.5 sec/rot) thoracic MDCT images were evaluated. We describe the differences in image quality and quantity between the different reconstruction kernels. We also propose a new reconstruction algorithm (ultra-low-dose reconstruction algorithm: ULR) for ultra-low-dose thoracic CT, to reduce noise and streak artifacts. We are convinced of the usefulness and possibility of ultra-low-dose thoracic MDCT with ULR algorithms for lung cancer screening.

Molecular analysis of congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS or Ondine's curse; OMIM 209880) is a disorder characterized by an idiopathic failure of the automatic control of breathing. CCHS is frequently complicated with neurocristopathies such as Hirschsprung's disease (HSCR). The genes involved in the RET-GDNF signaling and/or EDN3-EDNRB signaling pathways have been analyzed as candidates for CCHS; however, only a few patients have mutations of the RET, EDN3, and GDNF genes. Recently, mutations of the PHOX2B gene, especially polyalanine expansions, have been detected in two thirds of patients. We studied the RET, GDNF, GFRA1, PHOX2A, PHOX2B, HASH-1, EDN1, EDN3, EDNRB, and BDNF genes in seven patients with isolated CCHS and three patients with HSCR. We detected polyalanine expansions and a novel frameshift mutation of the PHOX2B gene in four patients and one patient, respectively. We also found several mutations of the RET, GFRA1, PHOX2A, and HASH-1 genes in patients with or without mutations of the PHOX2B gene. Our study confirmed the prominent role of mutations in the PHOX2B gene in the pathogenesis of CCHS. Mutations of the RET, GFRA1, PHOX2A, and HASH-1 genes may also be involved in the pathogenesis of CCHS. To make clear the pathogenesis of CCHS, the analysis of more cases and further candidates concerned with the development of the autonomic nervous system is required.