Ovalbumin modified by gamma irradiation alters its immunological functions and allergic responses

It is well known that gamma (gamma)-ray irradiation results in the alteration of biological function of bioactive materials such as proteins, saccharides and lipids. In this study the effect of gamma-irradiation on the chemical and immunological property of an allergen, ovalbumin (OVA), was investigated. Irradiation of more than 10 kGy resulted in the alteration of the structure of OVA. However, OVA treated with 10 kGy irradiation (10 kGy-OVA), but not 100 kGy-OVA, fully maintained immunological reactivity to a monoclonal antibody specific to the intact allergen (clone 14). Mice immunized with 10 kGy- as well as 100 kGy-OVA showed significantly lower antibody response to the allergen than those with intact OVA in a gamma-ray dosage-dependent manner. Especially immunization of both 10 kGy- and 100 kGy-OVA induced a significant decrease of OVA-specific IgE. Splenocytes of mice immunized with irradiated OVA showed a significant reduction in OVA-specific T cell proliferation and the secretion of Th1-type (IFN-gamma and IL-2) and Th2-type cytokines (IL-4 and IL-6). The expression of T cell activation markers such as CD25 and CD44 was also down-regulated in T cells of mice immunized with irradiated OVAs. These results suggest that gamma-ray irradiation of OVA suppress humoral and cellular immune responses specific to the allergen OVA, and the modification method with gamma-irradiation may be available for the control of allergy.     

Changes in DNA methylation patterns in subjects exposed to low-dose benzene

Aberrant DNA methylation patterns, including global hypomethylation, gene-specific hypermethylation/hypomethylation, and loss of imprinting (LOI), are common in acute myelogenous leukemia (AML) and other cancer tissues. We investigated for the first time whether such epigenetic changes are induced in healthy subjects by low-level exposure to benzene, a widespread pollutant associated with AML risk. Blood DNA samples and exposure data were obtained from subjects with different levels of benzene exposure, including 78 gas station attendants, 77 traffic police officers, and 58 unexposed referents in Milan, Italy (personal airborne benzene range, < 6-478 microg/m(3)). Bisulfite-PCR pyrosequencing was used to quantitate DNA methylation in long interspersed nuclear element-1 (LINE-1) and AluI repetitive elements as a surrogate of genome-wide methylation and examine gene-specific methylation of MAGE-1 and p15. Allele-specific pyrosequencing of the H19 gene was used to detect LOI in 96 subjects heterozygous for the H19 imprinting center G/A single-nucleotide polymorphism. Airborne benzene was associated with a significant reduction in LINE-1 (-2.33% for a 10-fold increase in airborne benzene levels; P = 0.009) and AluI (-1.00%; P = 0.027) methylation. Hypermethylation in p15 (+0.35%; P = 0.018) and hypomethylation in MAGE-1 (-0.49%; P = 0.049) were associated with increasing airborne benzene levels. LOI was found only in exposed subjects (4 of 73, 5.5%) and not in referents (0 of 23, 0.0%). However, LOI was not significantly associated with airborne benzene (P > 0.20). This is the first human study to link altered DNA methylation, reproducing the aberrant epigenetic patterns found in malignant cells, to low-level carcinogen exposure.     

Bilateral primary sensori-motor cortex activation of post-stroke mirror movements: an fMRI study

This fMRI study was undertaken to test whether the pathophysiological mechanism of mirror movements in hemiparetic stroke patients involves activation of the unaffected motor cortex. We studied 16 control subjects and 51 stroke patients. fMRI was performed at 1.5 T using a finger flexion-extension movement paradigm. The incidence of bilateral primary sensorimotor cortex activation was significantly increased during movements of the affected hand of stroke patients who showed mirror movements. Moreover, the incidence of bilateral primary sensorimotor cortex activation increased with the severity of mirror movements and primary sensorimotor cortex was activated bilaterally in all patients who showed sustained mirror movements. We conclude that the motor cortex activation on the non-stroke side is associated with mirror movements and is correlated with the severity of mirror movements. It seems that the pathophysiological mechanism of sustained mirror movements in stroke patients involves the unaffected motor cortex.     

Discrimination of tuberculous spondylitis from pyogenic spondylitis on MRI

OBJECTIVE: The purpose of this study was to determine the accuracy of MRI for discrimination between tuberculous spondylitis and pyogenic spondylitis. MATERIALS AND METHODS: MR images of 52 patients who had MRI of the spine and confirmed spondylitis were retrospectively reviewed. After review of medical records, we compared MRI findings in 20 patients with tuberculous spondylitis and 20 patients with pyogenic spondylitis. Statistical analysis was performed with the chi-square test. RESULTS: The reviewer identified tuberculous spondylitis with sensitivity, specificity, and accuracy of 100% (20/20), 80% (16/20), and 90% (36/40), and pyogenic spondylitis with sensitivity, specificity, and accuracy of 80% (16/20), 100% (20/20), and 90% (36/40), respectively. The patients with tuberculous spondylitis had a significantly higher incidence of MRI findings as follows (p < 0.05): a well-defined paraspinal abnormal signal (95% [19/20] in tuberculous vs 25% [5/20] in pyogenic), a thin and smooth abscess wall (95% [19/20] vs 15% [3/20]), combination of both findings (90% [18/20] vs 0% [0/20]), presence of paraspinal or intraosseous abscess (95% [19/20] vs 50% [10/20]), subligamentous spread to three or more vertebral levels (85% [17/20] vs 40% [8/20]), involvement of multiple vertebral bodies (60% [12/20] vs 25% [5/20]), thoracic spine involvement (40% [8/20] vs 10% [2/20]), and hyperintense signal on T2-weighted images (95% [19/20] vs 65% [13/20]). CONCLUSION: MRI was accurate for differentiation of tuberculous spondylitis from pyogenic spondylitis.     

Indocyanine green angiographic findings of obscure choroidal abnormalities in neurofibromatosis

We report two cases of choroidal neurofibromatosis, detected with the aid of indocyanine green angiography (ICGA) in patients with neurofibromatosis (NF)-1, otherwise having obscure findings based on ophthalmoscopy and fluoresceine angiography (FA). In case 1, the ophthalmoscopic exam showed diffuse bright or yellowish patched areas with irregular and blunt borders at the posterior pole. The FA showed multiple hyperfluorescent areas at the posterior pole in the early phase, which then showed more hyperfluorescence without leakage or extent in the late phase. The ICGA showed diffuse hypofluorescent areas in both the early and late phases, and the deep choroidal vessels were also visible. In case 2, the fundus showed no abnormal findings, and the FA showed weakly hypofluorescent areas with indefinite borders in both eyes. With the ICGA, these areas were more hypofluorescent and had clear borders. Choroidal involvement in NF-1 seems to occur more than expected. In selected cases, ICGA is a useful tool to be utilized when an ocular examination is conducted in a patient that has no definite findings based on the ophthalmoscope, B-scan, or FA tests.     

Mutagenicity of recombinant antihemophilic factor (GC-gamma AHF)

This study was carried out to evaluate the mutagenic potential of recombinant antihemophilic factor VIII (GC-gamma AHF). Salmonella typhimurium (S. typhimurium) reversion assay with/without histidine moiety, chromosomal aberration assay on Chinese hamster lung (CHL) fibroblast cells and in vivo micronucleus assay using mouse bone marrow cells and supravital micronucleus assay using peripheral blood were performed. GC-gamma AHF containing histidine did show inconsistent and irregular mutagenic effects on S. typhimurium TA98, TA100, TA1535 and TA1537 both in the absence and presence of the metabolic activation system, however, GC-gamma AHF without histidine showed no mutagenic effects regardless of the metabolic activation system, thus suggesting that the histidine moiety in GC-gamma AHF might cause inconsistent mutagenic effect. Also GC-gamma AHF did not increase the number of cells having structural or numerical chromosome aberration in the cytogenetic test. In classical and supravital micronucleus assay, no significant increases were observed in the occurrence of micronucleated polychromatic erythrocytes and micronucleated peripheral lymphocytes in male ICR mice. These results strongly indicate that GC-gamma AHF has no genetic toxicity under these experimental conditions.     

Evaluation of Prostate Cancer Stage Groups Updated in the 8th Edition of the American Joint Committee on Cancer Tumor–Node–Metastasis Staging Manual

Introduction

The American Joint Committee on Cancer (AJCC) tumor, node, metastasis classification system (TNM) staging manual has been updated and provides more specified stage grouping for prostate cancer (PCa). We aimed to validate the updated AJCC stage groups for PCa using a radical prostatectomy (RP) cohort.

Multiphasic perfusion computed tomography in hyperacute ischemic stroke: comparison with diffusion and perfusion magnetic resonance imaging

PURPOSE: The purpose of this study was to compare multiphasic perfusion computed tomography (CT) with diffusion and perfusion magnetic resonance imaging (MRI) in predicting final infarct volume, infarct growth, and clinical severity in patients with hyperacute ischemia untreated by thrombolytic therapy. METHOD: Multiphasic perfusion CT was performed in 19 patients with ischemic stroke within 6 hours of symptom onset. Two CT maps of peak and total perfusion were generated from CT data. Diffusion-weighted imaging (DWI) and perfusion MRI were obtained within 150 minutes after CT. Lesion volumes on CT and MRI were compared with final infarct volume and clinical scores, and mismatch on CT or MRI was compared with infarct growth. RESULTS: The lesion volume on the CT total perfusion map strongly correlated with MRI relative cerebral blood volume (rCBV), and that on the CT peak perfusion map strongly correlated with MRI relative cerebral blood flow (rCBF) and rCBV (P < 0.001). The lesion volume on unenhanced CT or DWI moderately correlated with final infarct volume, but only lesion volume on unenhanced CT weakly correlated with baseline clinical scores (P = 0.024). The lesion volumes on the CT peak perfusion map and MRI rCBF similarly correlated with final infarct volume and clinical scores and more strongly than those on mean transit time (MTT) or time to peak (TTP). DWI-rCBF or CT mismatch was more predictive of infarct growth than DWI-MTT or DWI-TTP mismatch. CONCLUSION: Multiphasic perfusion CT is useful and of comparable utility to diffusion and perfusion MRI for predicting final infarct volume, infarct growth, and clinical severity in acute ischemic stroke.     

CT features of systemic lupus erythematosus in patients with acute abdominal pain: emphasis on ischemic bowel disease

PURPOSE: To evaluate the computed tomographic (CT) features of systemic lupus erythematosus (SLE) in patients with acute abdominal pain. Special emphasis was placed on the analysis of ischemic bowel disease. MATERIALS AND METHODS: The authors retrospectively reviewed the images from 39 abdominal CT examinations performed in 33 patients with SLE and acute abdominal pain. Images were evaluated for bowel wall changes, mesenteric changes, fluid collection, retroperitoneal lymphadenopathy, peritoneal enhancement, and hepatomegaly as well as for changes in other abdominal organs. Ischemic bowel disease was diagnosed if at least three of the following signs were seen: bowel wall thickening, target sign, dilatation of intestinal segments, engorgement of mesenteric vessels, and increased attenuation of mesenteric fat. RESULTS: Thirty-one (79%) of the 39 examinations had CT findings diagnostic of ischemic bowel disease, including symmetric bowel wall thickening (n = 29), target sign (n = 26), and mesenteric vascular engorgement and haziness (n = 31). In 24 cases, bowel wall thickening was multifocal, with variable length, and did not appear to be confined to a single vascular territory. CONCLUSION: The most common CT finding in patients with SLE and acute abdominal pain is ischemic bowel disease. CT is useful for detecting the primary cause of gastrointestinal symptoms, planning treatment, and monitoring for infarction or perforation.