Effect of diacylglycerol on postprandial lipid metabolism in non-diabetic subjects with and without insulin resistance

The effects of diacylglycerol ingestion on postprandial lipid metabolism in non-diabetic subjects with and without insulin resistance were investigated. This was single dose ingestion study, in a double blind cross over manner and postprandial lipid concentrations were compared between diacylglycerol oil (DAG) and triacylglycerol oil (TAG) ingestion. The subjects were 18 male volunteers and homeostasis model assessment (HOMA-R) was used to classify them into insulin sensitive (IS, n=10, HOMA-R<2.0) and insulin resistant (IR, n=8, HOMA-R> or =2.0) groups. Fasting serum triglycerides (TG) and remnant-like particle cholesterol (RLP-C) correlated with HOMA-R and were significantly higher in the IR as compared to the IS group. Postprandial increments of TG and RLP-C after DAG ingestion were significantly lower as compared to those after TAG ingestion. In a case of TAG ingestion, their increments positively correlated with HOMA-R and were significantly higher in the IR as compared with the IS group. In contrast, their increments remained constant after DAG ingestion in both groups. In the IR group, the postprandial lipidemia were reduced after DAG ingestion to about half of those after TAG ingestion. In conclusion, DAG reduced postprandial lipidemia especially in subjects with insulin resistance and may be beneficial in preventing atherosclerosis and related diseases.     

Expression of cdc25B and cdc25A in medullary thyroid carcinoma: cdc25B expression level predicts a poor prognosis

Cdc25B and cdc25A phosphatases are prominent stimulators of cell cycle progression and have been suggested to play oncogenic roles. In this study, we immunohistochemically investigated the expression of these phosphatases in medullary thyroid carcinoma. Cdc25B was positive in 35.8% of cases examined. Its positivity was linked only to patient age. However, patients with cdc25B-positive tumors showed a significantly worse disease-free survival rate (P=0.0210) than those with cdc25B-negative tumors. Cdc25A was positive in only 17.2% of cases and was not related to clinicopathological parameters or prognosis. These findings suggest that cdc25B can be regarded as having prognostic significance and as a novel marker of biologically aggressive characteristics in this carcinoma.     

Ochtodene derivatives from the red alga Carpopeltis crispata

Red algae are well known as a source of halogenated monoterpenes such as derivatives of ochtodene. From Carpopeltis crispata, we have isolated four new ochtodene derivatives: dibromodichloro-, dibromochloro-, and bromodichlorocyclomonoterpenes. The structures of these monoterpenes were confirmed by NMR and mass spectroscopy and compared with spectral data in the literature.     

Enhancement of IL-7 following irradiation of fetal thymus

The effect of ionizing radiation on intra-thymic T cell development was investigated using a fetal thymic organ culture (FTOC) method in vitro. When double-negative (DN) fetal (day 15) thymocytes were co-cultured with an irradiated (25 Gy) fetal (day 15) thymus in the absence of direct contact or mitogenic stimulation, the induction of TCRgammadelta+ T cells was observed. About 50% of the TCRgammadelta+ T cells developed after 4-day-co-culture with the irradiated fetal thymus, whereas only a few TCRgammadelta+ T cells developed after co-culture with the non-irradiated fetal thymus. About 50% of the TCRgammadelta+ T cells were CD8+ cells with alphabeta heterodimeric chains. Cultured supernatants of the irradiated fetal thymi also induced the differentiation from DN thymocytes to CD8+ TCRgammadelta+ T cells after 3-day-culture. To clarify the factor in the cultured supernatants, several neutralizing antibodies (Abs) were used. Only anti-IL-7-Ab inhibited the differentiation from DN thymocytes to CD8+ TCRgammadelta+ T cells. RT-PCR revealed the increased expression of IL-7 mRNA in the fetal thymus 24 hours after radiation. Electron microscope studies demonstrated proliferative epithelial cells in the irradiated fetal thymus. These findings strongly suggest that fetal thymic epithelial cells affected by irradiation proliferate and enhance the production of IL-7, which induces the differentiation of CD8+ TCRgammadelta+ T cells from DN thymocytes.     

The neural origin generating early cortical components of SEP: Topographical analysis using temporal-second-order-differentiation of cortical SEPs

Summary In order to identify dipole generators of the N20/P20 and P25, we employed second-order-differentiation in the temporal dimension (temporal-second-order-differentiation; TSOD) with t=2 msec. The rate of variation in the voltage of cortical SEPs calculated by TSOD identified responses of each dipole, reflecting the density of neuronal firing. On topographic analysis, the distributions of N20/P20 and P25 conformed to the shape of gyrus better in the TSOD maps than in the isovoltage maps. The TSOD maps indicated that N20 and P25 were post-central components and that P20 was a pre-central one. Therefore, we concluded that the two dipoles generating N20/P20 and P25 were located in the posterior wall of the central sulcus (area 3b) and the crown (areas 1 and 2) of the post-central gyrus, respectively.     

KAI1 expression in thyroid neoplasms: its linkage with clinicopathologic features in papillary carcinoma

KAI1 is a metastasis suppressor gene located on human chromosome 11p11.2. Previous studies have shown that the down-regulation of KAI1 mRNA and decreased expression of its gene product are significantly linked to carcinoma progression, including metastatic ability. In this study, we investigated KAI1 protein expression in thyroid neoplasms. KAI1 overexpression was observed in 64.0% of papillary carcinoma cases, and the incidence was significantly higher than in cases of follicular carcinoma (20.0%) (p = 0.0001). In papillary carcinomas, decreased KAI1 expression was frequently observed in cases invading beyond the thyroid capsule (p = 0.001), as well as in lymph node metastases (p = 0.0047) and poorly differentiated lesions (p = 0.0299). Furthermore, in anaplastic carcinoma, the incidence of KAI1 overexpression was lower than in papillary carcinoma (p < 0.0001), and only 4.2% of the cases overexpressed this gene. These results suggest that KAI1 down-regulation is significantly related to the progression of papillary carcinoma, including lymph node metastasis, and its anaplastic transformation.     

Monoclonal antibodies to human factor VII: production of immunodepleted plasma for VII:C assays.

A high affinity monoclonal antibody to factor VII (RFF-VII/1), coupled to sepharose, was used to immunodeplete factor VII from normal plasma. The plasma could be used as a substrate in a one stage coagulation assay and performed as well as, or better than, commercially available factor VII deficient plasma or plasma from congenitally deficient factor VII patients. Plasma from normal donors (n = 20), patients with liver disease (n = 20), and patients receiving warfarin (n = 20), or congenitally factor VII deficient patients (n = 7) was assayed for VII:C concentration in a one stage coagulation assay. The concentration of VII:C detected with the immunodepleted plasma substrate was comparable in all cases with that seen with a commercially available substrate (r = 0.95).     

A unique pattern of up- and down-regulation of chemokine receptor CXCR3 on inflammation-inducing Th1 cells

Chemokine receptor CXCR3 and its CXC ligands play major roles in Th1 cell-induced inflammatory processes. Here, we examined the expression of CXCR3 by TCR-transgenic Th1 lymphocytes that induce ocular inflammation in mice expressing the target antigen in their lenses. The essential role of CXCR3 in this model was indicated by the observation that the ocular inflammation was significantly blocked by an antibody against this receptor. CXCR3 expression by Th1 cells was elevated during their initial activation in culture and further increased during the consecutive incubation with IL-2. However, CXCR3 expression declined dramatically during the ensuing antigenic reactivation, in parallel with down-regulation of its mRNA. Yet, reactivated Th1 cells exhibited the highest degree of pathogenicity when adoptively transferred into recipients. Transferred reactivated Th1 cells proliferated vigorously and re-expressed CXCR3 while residing in the spleen of recipient mice, reaching approximately 85% positivity 4 days post cell transfer when their massive migration to the target eyes began. Importantly, infiltrating Th1 cells underwent profound phenotypic changes in the eye that closely resembled those seen during reactivation of Th1 cells in vitro and included down-regulation of CXCR3. These observations thus show that expression of CXCR3, a major participant in Th1-induced inflammation, fluctuates profoundly during cell activation and migration and is down-regulated upon re-exposure of these cells to the antigen, in vitro or in the target organ.     

Association of MBL gene polymorphisms with major bacterial infection in patients treated with high-dose chemotherapy and autologous PBSCT

A growing body of evidence indicates that genetic factors are involved in an increased risk of infection. We investigated whether mannose-binding lectin (MBL) gene polymorphisms that cause low levels of MBL are associated with the occurrence of major infections in patients, mainly bearing hematological malignancies, after high-dose chemotherapy (HDT) rescued by autologous peripheral blood stem cell transplantation (auto-PBSCT). A retrospective evaluation of 113 patients treated with HDT and auto-PBSCT revealed that the low-producing genotypes, B/B and B/LXA, were associated with major bacterial infection (P=0.0016, OR 7.9). We next performed a nation-wide large-scale study to assess the allele frequency of the MBL coding mutation in a total of 2623 healthy individuals in Japan. The frequency of allele B was estimated to be approximately 0.2, almost the same in seven different areas of Japan. This common occurrence suggests that MBL deficiency may play an important role in the clinical settings of immunosuppression.