Determination of medullasin levels for the diagnosis of multiple sclerosis

Medullasin levels in granulocytes of patients with neurological diseases and healthy volunteers were determined by the enzyme immunoassay using mouse monoclonal antibodies against human medullasin and o-phenylenediamine-H2O2 as the detection system of the enzyme activity. One hundred twenty-one out of 159 patients with multiple sclerosis (76.1%) showed positive results (above means of normals + 2SD) in this test, while only 16.9% (24/142) of patients with non-inflammatory neurological diseases had positive results. This enzyme immunoassay method for medullasin is considered to be an useful paraclinical test for the diagnosis of multiple sclerosis.     

Enlarged longitudinal dose profiles in cone-beam CT and the need for modified dosimetry

In order to examine phantom length necessary to assess radiation dose delivered to patients in cone-beam CT with an enlarged beamwidth, we measured dose profiles in cylindrical phantoms of sufficient length using a prototype 256-slice CT-scanner developed at our institute. Dose profiles parallel to the rotation axis were measured at the central and peripheral positions in PMMA (polymethylmethacrylate) phantoms of 160 or 320 mm diameter and 900 mm length. For practical application, we joined unit cylinders (150 mm long) together to provide phantoms of 900 mm length. Dose profiles were measured with a pin photodiode sensor having a sensitive region of approximately 2.8 x 2.8 mm2 and 2.7 mm thickness. Beamwidths of the scanner were varied from 20 to 138 mm. Dose profile integrals (DPI) were calculated using the measured dose profiles for various beamwidths and integration ranges. For the body phantom (320-mm-diam phantom), 76% of the DPI was represented for a 20 mm beamwidth and 60% was represented for a 138 mm beamwidth if dose profiles were integrated over a 100 mm range, while more than 90% of the DPI was represented for beamwidths between 20 and 138 mm if integration was carried out over a 300 mm range. The phantom length and integration range for dosimetry of cone-beam CT needed to be more than 300 mm to represent more than 90% of the DPI for the body phantom with the beamwidth of more than 20 mm. Although we reached this conclusion using the prototype 256-slice CT-scanner, it may be applied to other multislice CT-scanners as well.     

Computer-Aided Diagnosis for Detection of Lacunar Infarcts on MR Images: ROC Analysis of Radiologists’ Performance

The purpose of this study was to retrospectively evaluate radiologist performance in detection of lacunar infarcts on T1- and T2-weighted images, without and with the use of a computer-aided diagnosis (CAD) scheme. Thirty T1-weighted and 30 T2-weighted MR images obtained from 30 patients were used for assessing observer performance. These images were acquired using the fast spin-echo sequence with a 1.5-T MR imaging scanner. The group included 15 patients (age range, 48-83 years; mean age, 67.2 years; 10 men and five women) with a lacunar infarct and 15 patients (age range, 39-76 years; mean age, 64.0 years; eight men and seven women) without lacunar infarcts. Nine radiologists participated in the study. The radiologists initially interpreted the T1- and T2-weighted images without and then with the use of CAD, which indicated their confidence levels regarding the presence (or absence) of lacunar infarcts and the most likely position of a lesion on each MR scan. The observers' performance without and with the computer output was evaluated by performing receiver operating characteristic analysis. For the nine radiologists, the mean area under the best-fit binormal receiver operating characteristic curve plotted for unit square values of radiologists who interpreted the images without and with the scheme were 0.891 and 0.937, respectively. The performance of the radiologists improved significantly when they used the computer output (p=0.032). The CAD scheme has potential to improve the accuracy of radiologists' performance in detection of lacunar infarcts.     

Pathological classification of hepatic inflammatory pseudotumor with respect to IgG4-related disease.

Recently, much attention has focused on IgG4-related disease, which is characterized by abundant IgG4-positive plasma cell infiltration and high serum IgG4 levels. IgG4-related disease sometimes manifests as tumorous lesions, and its relationship to inflammatory pseudotumor has been suggested. In this study, we examined clinicopathological features of a total of 16 cases of hepatic inflammatory pseudotumor (11 men and 5 women with an average age of 67 years) with respect to IgG4-related disease. The tumors could be pathologically classified into two types: fibrohistiocytic (10 cases) and lymphoplasmacytic (6 cases). Fibrohistiocytic inflammatory pseudotumors were characterized by xanthogranulomatous inflammation, multinucleated giant cells, and neutrophilic infiltration, and mostly occurred in the peripheral hepatic parenchyma as mass-forming lesions. In contrast, lymphoplasmacytic inflammatory pseudotumors showed diffuse lymphoplasmacytic infiltration and prominent eosinophilic infiltration, and were all found around the hepatic hilum. In addition, venous occlusion with little inflammation and cholangitis without periductal fibrosis were frequently observed in the fibrohistiocytic type, whereas obliterative phlebitis and cholangitis with periductal fibrosis were common features of the lymphoplasmacytic type. Interestingly, IgG4-positive plasma cells were significantly more numerous in the lymphoplasmacytic than fibrohistiocytic type. However, two of the fibrohistiocytic inflammatory pseudotumors had relatively many IgG4-positive plasma cells. In conclusion, hepatic inflammatory pseudotumor could be classified into two types based on clinicopathological characteristics. The lymphoplasmacytic type is unique, and could belong to the so-called IgG4-related diseases. In contrast, the fibrohistiocytic type might still be a heterogeneous group of disorders. This latter type seems pathologically different from IgG4-related disease, although cases with relatively abundant IgG4-positive plasma cells should be differentiated from IgG4-related disease with secondary histopathologic modifications.     

Autopsy case of primary myelofibrosis in which myeloid sarcoma was the initial manifestation of tumor progression

Myeloid sarcoma (MyS) is defined as an extramedullary tumor-forming neoplasm consisting of immature myeloid cells with/without maturation. We experienced a case involving a 68-year-old Japanese male patient who had been followed-up for four years with a diagnosis of chronic idiopathic myelofibrosis/primary myelofibrosis (PMF) and noticed a painful mass in his left axilla. A wedge biopsy characterized the lesion as MyS that displayed megakaryoblastic/megakaryocytic differentiation. As his complete blood count included a few myeloid blasts (1% of WBC) and a bone marrow biopsy detected fibrosis without evidence of acute myelogenous leukemia (AML), a diagnosis of extramedullary blastic transformation of PMF was made, which was confirmed later by V617F mutation in Janus kinase-2 in both initial bone marrow biopsy and axillary tumor biopsy specimens. The patient died of pneumonia eight months after developing the axillary tumor. At autopsy, multiple MyS masses were detected in his soft tissue, but his bone marrow only contained fibrosis. Although MyS rarely develops before the leukemic transformation of PMF, no evidence of AML could be found in the patient's bone marrow at any point during the course of his disease. Thus, it is possible that the blasts in his peripheral blood were derived from the remaining MyS. Furthermore, the present case indicates that extramedullary blastic transformation, which is occasionally seen in CML, can also occur in PMF. Therefore, it is important to recognize that there is a wide variation in the pathogeneses of MyS and PMF.     

Age-related dysfunction of the lacrimal gland and oxidative stress: evidence from the Cu,Zn-superoxide dismutase-1 (Sod1) knockout mice

An imbalance between free radical generation and radical scavenging antioxidant systems results in oxidative stress, which has been associated with cell injury observed in many age-related diseases. The superoxide dismutase (SOD) family is a major antioxidant system, and deficiency of Cu,Zn-superoxide dismutase-1 (Sod1) in mice leads to many different phenotypes that resemble accelerated aging. In this study we examined the morphologic features and the secretory functions of the lacrimal glands in Sod1(-/-) mice. Lacrimal glands showed atrophy of acinar units; fibrosis; infiltration with CD4(+) T cells, monocytes, and neutrophils; increased staining with both 4-hydroxy-2-nonenal and 8-hydroxy-2'-deoxyguanosine; increases in apoptotic cells; and the presence of the epithelial-mesenchymal transition in senescent Sod1(-/-) mice. Electron microscopy findings revealed evidence of epithelial-mesenchymal transition, presence of swollen and degenerated mitochondria, and the presence of apoptotic cell death in the lacrimal glands of senescent Sod1(-/-) mice. These alterations were also associated with the accumulation of secretory vesicles in acinar epithelial cells, decreased production of both stimulated and nonstimulated tears, and a decline in total protein secretion from the lacrimal glands. Our results suggest that Sod1(-/-) mice may be a good model system in which to study the mechanism of reactive oxygen species-mediated lacrimal gland alterations.     

A comparison of epidermal growth factor receptor expression in malignant peritoneal and pleural mesothelioma

An evaluation of epidermal growth factor receptor (EGFR) phenotypic expression in malignant pleural and peritoneal mesothelioma was undertaken, using immunohistochemical (IHC) and fluorescence in situ hybridization (FISH) analysis. Thirty-eight malignant mesothelioma (MM) specimens were subjected to IHC staining and FISH to evaluate the expression of EGFR protein and gene status. Overall positive IHC reaction was detected in 20/38 (53%) cases, in 11/22 (50%) pleural MM, and in 9/16 (56%) peritoneal MM. Our study confirmed that EGFR membranous expression is a common feature in MM, but not in benign mesothelial lesion. Thirty-seven cases did not show a gene copy number gain. Only one case showed a copy number gain. The protein overexpression of EGFR was not related to a gene copy number gain.