Inhibitory oligodeoxynucleotides (ODNs), which are capable of blocking CpG-induced inflammation, have been anticipated to be beneficial therapeutic agents for autoimmune diseases. In this study, we show that GpC ODN, which inverted the cytosine guanine sequence of CpG motif to guanine cytosine sequence, is an inhibitory ODN. The inhibitory effects of GpC ODN on CpG ODN-induced immune activation were confirmed by cytokine assay using splenocytes from lupus-prone MRL-lpr/lpr mice. In vivo, injecting MRL-lpr/lpr mice with GpC ODN did not reduce the deposition of IgG and C3 in the glomeruli, the serum level of IL-12, the serum level of rheumatoid factors and anti-ds DNA antibody, or alter the composition of IgG isotypes of anti-ds DNA antibody. However, the mice in the GpC group showed less proteinuria, significantly lower blood urea nitrogen levels (BUN) and significantly prolonged survival. Our results suggest that inhibitory ODNs, such as GpC ODN, have the potential to become a treatment for autoimmune diseases, like lupus nephritis.
In this communication, we studied whether 3D-CT angiography (3D-CTA) gives us enough information for a safe operation without those from conventional catheter angiography (CCA) in patients with ruptured aneurysms. Between December 1996 and September 2005, we treated 162 consecutive patients with ruptured aneurysms in the acute stage based on 3D-CTA findings. One hundred sixty-two ruptured aneurysms, including 64 associated unruptured aneurysms, were detected using 3D-CTA. CCA was performed in nine (5.6%) of the 162 patients after 3D-CTA. They were four dissecting vertebral artery aneurysms, two basilar tip aneurysms, one basilar artery-superior cerebellar artery (BA-SCA), one previously clipped BA-SCA and one internal carotid-posterior communicating artery aneurysm. All ruptured aneurysms confirmed at surgery were treated successfully. The lack of information on CCA did not lead any neurological deficits or difficulties in the surgical procedure. 3D-CTA was of high diagnostic value compatible with CCA and yielded important information such as the configuration of the aneurysmal sac and neck, calcification in the aneurysmal wall, and the aneurysms' anatomic relation with adjacent vessels and bone structures. We suggest that 3D-CTA can replace CCA in the diagnosis of ruptured aneurysms and that most of ruptured aneurysms can be operated by using only 3D-CTA without CCA.
Reportedly, bacterial DNA containing unmethylated cytosine-guanosine dinucleotide motif-containing oligodeoxynucleotides (CpG-ODNs) can induce Th1-type adjuvant effects. We produced autoantibodies and induced hepatitis in mice using extracted proteins from human hepatocytes with CpG-ODNs as adjuvant. Western blot analysis was performed of sera from immunized mice and two patients with autoimmune hepatitis (AIH). When a common band was detected, N-terminal amino acid sequencing was performed to determine its site. For detection of antibodies against the identified protein (calreticulin), ELISA was performed of sera of 50 patients with AIH: 45 with primary biliary cirrhosis (PBC), 24 with chronic hepatitis C (CH), and 24 healthy controls. Mice were immunized with calreticulin protein with CpG-ODNs as adjuvant. Several reacted bands were detected in their sera; in addition, a common band to the sera of patients with AIH was detected at 60 kDa. Subsequent N-terminal amino acid sequencing revealed that the protein was human calreticulin. ELISA showed that, of patients with AIH, PBC, and CH, 30.0% (15/50), 17.8% (8/45), and 12.5% (3/24), respectively, were positive for anti-calreticulin antibodies. Splenocytes from immunized mice produced IFN-γ after they were pulsed with calreticulin protein. Histological analyses of liver specimens taken from mice immunized with calreticulin protein together with CpG-ODN s showed spotty and focal necrosis. Immunofluorescence analysis showed increased expression of calreticulin in the liver treated with CpG-ODNs. These results suggest that a breakthrough of immune self-tolerance to calreticulin is induced with CpG-ODNs as adjuvant and that calreticulin protein might be a target antigen in this model.
During the initial 8 months period of 18F-FDG PET/CT examination in our institution eleven cases of double cancers were detected. Eight cases were simultaneous second cancers and 3 cases are consecutive cancers. All cases are clinical ones and were referred from both outside hospitals and our own hospital. 18F-FDG PET/CT examination were utilized either to determine the extent of tumor or to stage the cancer or to detect recurrent tumors during the follow-up period. During the 8-months period 964 cases were studied. Therefore, the detection rates of simultaneous and consecutive cancers are 0.83% and 0.31% respectively. All together the detection rate of double cancer was 1.14%. To gain the general conception of double cancers the authors reviewed the autopsy registry of Japanese Society of Pathology during the four years from 2000 through 2003, and tabulated the combination of primary and second cancers. Frequently found combination of cancers were cancers of the thyroid, lung, stomach, liver, biliary tract, colon, rectum, and prostate. 18F-FDG PET/CT examination seems to be very useful in the management of cancer patients in terms of whole patient care.