B cell antigen receptor signal strength and peripheral B cell development are regulated by a 9-O-acetyl sialic acid esterase

We show that the enzymatic acetylation and deacetylation of a cell surface carbohydrate controls B cell development, signaling, and immunological tolerance. Mice with a mutation in sialate:O-acetyl esterase, an enzyme that specifically removes acetyl moieties from the 9-OH position of α2–6-linked sialic acid, exhibit enhanced B cell receptor (BCR) activation, defects in peripheral B cell development, and spontaneously develop antichromatin autoantibodies and glomerular immune complex deposits. The 9-O-acetylation state of sialic acid regulates the function of CD22, a Siglec that functions in vivo as an inhibitor of BCR signaling. These results describe a novel catalytic regulator of B cell signaling and underscore the crucial role of inhibitory signaling in the maintenance of immunological tolerance in the B lineage.     

Cranioplasty using the patient's autogenous bone preserved by freezing--an examination of post-operative infection rates

The current technique for cranioplasty using artificial bone requires further improvement with regard to infection, strength and comfort through good fitting. We have carried out cranioplasty using the patient's autogenous bone flap obtained during first surgery. It was immersed in 200 mg of Amikacin Sulphate, and frozen at -16 degrees C until its use in cranioplasty. From 1980 to 1998, cranioplasty has been carried out on 206 patients. They consisted of 118 males and 88 females, and their age ranged in our institute from 1 to 81; average age 51.1. Ruptured aneurysm (48%), head injury (14%), intracranial hemorrhage (23%) and cerebral infarction (12%) were the major causes requiring decompression surgery. We analyse the bone preservation period and the time between cranioplasty and the onset of infection. The infection rates per bone preservation periods, the causes of decompression and age groups are studied. Of the 208 case studies, infection necessitating bone removal or debridement was noted in 8 cases (3.88%). Average bone preservation period in the infected group was 31.1 days as compared with 54.9 days for the non-infected group (p < 0.05). Not patient age but the type of head injury is also a significant factor in post cranioplasty infection.     

Involvement of IL-2/IL-2R system activation by parasite antigen in polyclonal expansion of CD4(+)25(+) HTLV-1-infected T-cells in human carriers of both HTLV-1 and S. stercoralis

The intermediate state of HTLV-1 infection, often found in individuals dually infected with Strongyloides stercoralis (S. stercoralis) and HTLV-1, is assumed to be a preleukemic state of adult T-cell leukemia (ATL). To investigate the effects of S. stercoralis superinfection on the natural history of HTLV-1 infection, we characterized peripheral blood samples of these individuals in Okinawa, Japan, an endemic area for both HTLV-1 and S. stercoralis and we studied effects of the parasite antigen on T-cells. The dually infected individuals showed a significantly higher provirus load and an increase in CD4(+)25(+) T cell population, with a significant, positive correlation. This increase was attributable to polyclonal expansion of HTLV-1-infected cells, as demonstrated by inverse-long PCR analysis of the integration sites. S. stercoralis antigen activated the IL-2 promoter in reporter gene assays, induced production of IL-2 by PBMC in vitro, and supported growth of IL-2 dependent cell lines immortalized by HTLV-1 infection or the transduction of Tax. Taken collectively, these results indicate that S. stercoralis infection induces polyclonal expansion of HTLV-1-infected cells by activating the IL-2/IL-2R system in dually infected carriers, an event which may be a precipitating factor for ATL and inflammatory diseases.     

Radiation exposure in CT

The use of CT has increased rapidly in the past two decades, in part because of the development of helical CT and multidetector row CT. The benefits obtained by CT are not, however, without risks. This paper emphasizes the importance of keeping radiation doses during CT procedures as low as reasonably possible, especially for pediatric and small adult patients. In order to evaluate the risk of exposure, precise dosimetry is important. This paper introduces a new film dosimetry system that can be used easily in any institution and with any CT apparatus.     

CT and MR imaging of desmoplastic fibroblastoma

Desmoplastic fibroblastoma (collagenous fibroma) developing as a slowly enlarging lower abdominal mass is described. The lesion had inhomogeneous low signal intensity (SI) on T1-weighted images, and mixed SI as low SI within high SI on T2-weighted images. On post-contrast T1-weighted images, the mass showed inhomogeneous enhancement. Histologically, the areas showing low SI on both post-contrast T1- and T2-weighted images consisted of dense collagenous components and reduced cellularity compared with the areas showing high SI on them.     

Aberrant methylation and histone deacetylation of cyclooxygenase 2 in gastric cancer.

Cyclooxygenase 2 plays a critical role in the development of gastrointestinal cancers in both human and animal models. About 80% of the gastric cancer showed a high level of expression of cyclooxygenase 2, but a subset of cases do not express without unknown reason. Aberrant methylation of CpG island of COX-2 was examined by using a series of gastric cancer cell lines and primary gastric cancers. Two out of 8 cell lines (25%) and 11 out of 93 (12%) primary cancers showed aberrant methylation of the 5' region of COX-2. Methylation of COX-2 was closely associated with loss of expression and treatment of methylation inhibitor, 5-deoxy-2'-azacytidine restored the expression of COX-2. A combined treatment of 5-deoxy-2'-azacytidine and a histone deacetylese inhibitor, trichostatin A, restored re-expression of the gene synergistically and chromatin immunoprecipitation analysis revealed that histone of methylated COX-2 promoter is deacetylated, indicating the role of cytosine methylation and histone deacetylation in the silencing of the gene. These results indicate that a subset of gastric cancer with COX-2 methylation evolves through the pathway that is independent of COX-2 expression and that COX-2 inhibitor may not be useful to induce apoptosis in these cases.     

Effect of Mass Screening for Breast Cancer from the Aspect of Psychosocial Assessment of the Quality of Life

To assess the quality of life (QOL) in patients with breast cancer receiving mass screening, a collaborative matched case-control study was conducted in nine hospitals throughout Japan. A total of 122 patients detected by mass screening (study group) and 226 patients found in out-patient clinics (control group) were assessed psychosocially on the basis of questionnaire information. The incidence of patients with early stage breast cancer was significantly higher in the study group than in the control group ( P <0.05). Chest wall pain was observed in 35.2% of the study group and in 46.5% of the control group ( P <0.05). Although control patients were more optimistic than study group patients, disturbed daily life and anxiety about recurrence were a little more frequent in the former group than in the latter. In particular, shoulder stiffness was frequently seen in the control group ( P <0.05). Early detection and information do not create anxiety in mass screening patients ( P <0.01). We should recommend mass screening to patients to detect early stage breast cancer and provide better QOL.     

Role of P-Glycoprotein in Ocular Clearance of Rhodamine 123 in Rabbits

Pharmaceutical Research -