Deletion of distal promoter of VCXA in a patient with X-linked ichthyosis associated with borderline mental retardation

BACKGROUND: X-linked ichthyosis (XLI) is caused by deficiency of steroid sulfatase (STS) activity. About 90% XLI patients have large deletions involving the entire STS gene and flanking regions. Recently, VCXA, which is located approximately 0.7Mb telomeric to the STS gene, was reported as a candidate gene for mental retardation (MR) in patients with XLI. OBJECTIVE: To delineate the X-chromosomal deletion of a XLI patient with borderline mental retardation. METHODS: We carried out FISH analysis to show that the whole STS gene is deleted, and PCR analysis for fine-scale deletion mapping. RESULTS: The deleted segment is approximately 1.6Mb in size, and includes the entire STS and VCXB1 genes. VCXA itself is intact, but its promoter is deleted. CONCLUSION: A deletion that includes the VCXA promoter is associated with borderline mental retardation in a patient with XLI.     

Primary cutaneous T-cell lymphoma of unspecified type with cytotoxic phenotype: Clinicopathological analysis of 27 patients

The objective of our study was to investigate the clinicopathological features of the currently ill-defined subtype of primary cutaneous T-cell lymphoma of unspecified type (CTCLU) with a cytotoxic phenotype and no Epstein–Barr virus (EBV) association. A series of 27 patients with CTCLU (median age 49 years; range 25–87 years; 18 men) was reviewed. Performance status scores above 1 (7%), clinical stages above 2 (15%), B symptoms (26%), extracutaneous involvement (30%), and a fatal course within 1 year of diagnosis (19%) were observed infrequently. The International Prognostic Index was high or high to intermediate in 11%, and the Prognostic Index for Peripheral T-cell Lymphoma unspecified was above group 2 in 22%. Notably, the rates of spontaneous regression and T-cell receptor gene rearrangements by polymerase chain reaction analysis were seen in 26 and 17% of our cases, respectively. Histologically, 22 patients had subcutaneous involvement of whom eight showed a lethal clinical course, and five patients without subcutaneous involvement were all survivors. Immunophenotypical and morphological features allowed us to subclassify our cases according to the following four categories: (1) epidermotropic CD8⁺ T-cell lymphoma ( n  = 5); (2) cutaneous γ/δ T-cell lymphoma ( n  = 8); (3) cutaneous α/β pleomorphic T-cell lymphoma ( n  = 8); and (4) cutaneous medium/large pleomorphic T-cell lymphoma, not otherwise specified ( n  = 6). All four of these groups of lymphomas exhibited a relatively favorable clinical course compared to previous reports. However, epidermotropic CD8⁺ T-cell lymphoma appeared to be unique with a higher ratio (80%) of spontaneous regression, a lower ratio (40%) of subcutaneous involvement, and a more favorable clinical course than the other three subcategories. ( Cancer Sci 2009; 100: 33–41)     

Phosphoinositide 3-kinase inhibitor (wortmannin) inhibits pancreatic cancer cell motility and migration induced by hyaluronan in vitro and peritoneal metastasis in vivo

In order to block peritoneal metastasis of pancreatic cancer cells, we have attempted to block the signal transduction pathway involving hyaluronan (HA), Src, phosphoinositide 3-kinase (PI3K) and Akt. We examined the effects of Src, PI3K and Akt inhibitors on pancreatic cancer cell motility, invasion and metastasis. The pancreatic cancer cell line SW1990, known to cause peritoneal metastasis efficiently in nude mice, was used in this study. SW1990 cells were stimulated by HA to induce Akt phosphorylation. Then, the inhibitory effects of PI3K and Src kinase inhibitors were examined. Cell motility and cell migration assays were adopted to assess the cancer cell motility and its migration capability. We also examined the therapeutic efficacies of PI3K inhibitor wortmannin on peritoneal metastasis of SW1990 cells in the nude mouse model. Stimulation of SW1990 cells by HA markedly induced the Src-PI3K-Akt signaling, thus enhancing cancer cell motility and its migration. Significantly, we found that wortmannin could exert marked inhibition of the peritoneal metastasis of SW1990 in nude mice in vivo . These findings indicate that the PI3K-Akt signaling pathway plays an essential role in peritoneal metastasis and PI3K inhibitors such as wortmannin can be novel modalities to prevent peritoneal metastasis of invasive cancers such as pancreatic cancer. ( Cancer Sci 2009; 100: 770–777)     

Association of Estimated Salt and Miso Intake with the Prevalence of Obesity in People with Type 2 Diabetes: A Cross-Sectional Study

Salt intake is often estimated by the amount of sodium excreted in urine, and miso has been reported to increase it. This cross-sectional study investigated the relationship between obesity and high estimated salt intake with and without habitual miso consumption. Estimates of salt intake (g/day) were calculated using urinary sodium excretion, and a high estimated intake was defined as greater than the median amount of 9.5 g/day. Participants were divided into four groups based on estimated salt intake and miso consumption. Among 300 people, the proportions of obesity were 77.8% (n = 14/18), 40.2% (n = 53/132), 26.0% (n = 33/127), and 34.8% (n = 8/23) in the (+/−), (+/+), (−/+), and (−/−) groups of high estimated salt intake/habitual miso consumption, respectively. Compared with the (+/−) group, the adjusted odds ratios for obesity were 0.07 (95% confidence interval (CI): 0.02–0.26, p < 0.001), 0.16 (95% CI: 0.03–0.76, p = 0.022), and 0.14 (95% CI: 0.04–0.51, p = 0.003) in the (−/+), (−/−), and (+/+) groups, respectively. The presence of obesity was not much higher in people with high estimated salt intake with habitual miso consumption than that in people without. Clinicians should be aware that miso consumption promotes salt excretion, which may lead to an apparently higher estimated salt intake than actual.     

Biliary anatomy on 3D MRCP: Comparison of volume‐rendering and maximum‐intensity‐projection algorithms

Purpose

To compare volume‐rendering (VR) and maximum‐intensity‐projection (MIP) of three‐dimensional T2‐weighted turbo spin‐echo magnetic resonance cholangiopancreatography using a free‐breathing navigator‐triggered prospective acquisition correction (3D‐TSE‐PACE‐MRCP) to define biliary anatomies.

Materials and Methods

VR and MIP images of 3D‐TSE‐PACE‐MRCP for 102 patients were retrospectively evaluated. Interpretation of cystic duct variation and biliary branching patterns of each image were recorded independently by two radiologists in a blinded fashion. Interpretation confidence on a five‐point scale was compared using the Wilcoxon signed‐rank test. The McNemar test was used to compare the accuracies of each reformation with the reference standard obtained by consensus interpretation of both the images and source images.

Results

The reference standard identified all biliary bifurcations and 95 of 102 cystic duct confluences (93.1%). VR findings agreed with the reference standard findings more often than MIP with regard to cystic duct variation (94 [92.2%] vs. 76 [74.5%], P < 0.01) while there was no significant difference for biliary branching patterns (99 [97.1%] vs. 92 [90.2%], P = 0.092). The mean confidence score was significantly higher with VR than MIP with regard to both cystic duct variation and biliary branching patterns (3.7 vs. 2.4; P < 0.01; 4.1 vs. 3.3; P < 0.01).

Conclusion

VR reformation of 3D‐TSE‐PACE‐MRCP defines biliary anatomies more accurately than MIP. J. Magn. Reson. Imaging 2009;29:601–606. © 2009 Wiley‐Liss, Inc.

     

“Sukeroku sign” and “dent internal-capsule sign”—identification guide for targeting the subthalamic nucleus for placement of deep brain stimulation electrodes

Introduction  The purpose of this study was to assess the usefulness of signs (“Sukeroku sign” and “dent internal-capsule sign”) for the recognition of subthalamic nucleus (STN). Materials and methods  Five Parkinson’s disease cases in which there was a successful placement of deep brain stimulation (DBS) electrodes at the STN were retrospectively reviewed. Five radiologists who were not engaged in localization of STNs in clinical practice were asked to locate the STNs before and after instructions on the signs. We evaluated the deviation between the reader-located points and the location of the DBS electrode for which there had been a successful installation. Results  After instruction, there was a significant reduction in the deviation between the reader-located points and the DBS electrode. The time required for localization was also reduced after the instructions. Conclusion  Sukeroku sign and dent internal-capsule sign are feasible indicators of STN and seem to be useful in helping to identify the STN.     

Biscoclaurine alkaloid cepharanthine inhibits the growth of primary effusion lymphoma in vitro and in vivo and induces apoptosis via suppression of the NF‐κB pathway

Primary effusion lymphoma (PEL) is a unique and recently identified non‐Hodgkin's lymphoma that was originally identified in patients with AIDS. PEL is caused by the Kaposi sarcoma‐associated herpes virus (KSHV/HHV‐8) and shows a peculiar presentation involving liquid growth in the serous body cavity and a poor prognosis. As the nuclear factor (NF)‐ κ B pathway is activated in PEL and plays a central role in oncogenesis, we examined the effect of a biscoclaurine alkaloid, cepharanthine (CEP) on PEL derived cell lines (BCBL‐1, TY‐1 and RM‐P1), in vitro and in vivo. An methylthiotetrazole assay revealed that the cell proliferation of PEL cell lines was significantly suppressed by the addition of CEP (1–10 μg/ml). CEP also inhibited NF‐ κ B activation and induced apoptotic cell death in PEL cell lines. We established a PEL animal model by intraperitoneal injection of BCBL‐1, which led to the development of ascites and diffuse infiltration of organs, without obvious solid lymphoma formation, which resembles the diffuse nature of human PEL. Intraperitoneal administration of CEP inhibited ascites formation and diffuse infiltration of BCBL‐1 without significant systemic toxicity in this model. These results indicate that NF‐ κ B could be an ideal molecular target for treating PEL and that CEP is quite useful as a unique therapeutic agent for PEL. © 2009 UICC