Questionnaire survey on pharmacists' roles among non- and health care professionals in medium-sized cities in Japan.

Although the scope of pharmacists' work has expanded in Japan, people's perception of this is unclear. To contribute to medical care together with non- and health care professionals, clarifying the perceptions of these groups is important to best utilize pharmacist professionals. We conducted a cross-sectional questionnaire survey among non-health care professionals (n = 487) and nurses (n = 151), medical doctors (n = 133), and pharmacists (n = 204) regarding the work of pharmacists. The questionnaire comprised 56 items in four categories associated with the roles of pharmacists. For each questionnaire item, we performed logistic regression analysis to compare pharmacists' opinions with those of other professionals and non-health care professionals. Opinions were similar between pharmacists and nurses or medical doctors regarding "collecting patient information" and "providing drug information to patients." However, there were differences in perceptions regarding "medical collaboration" (nurses; 8/23 items, physicians; 11/23 items) and "community medicine" (nurses; 9/15 items, physicians; 11/15 items), and pharmacists themselves perceived greater roles related to health care collaboration and community health care. Perceptions of non-health care professionals were poorer than those of pharmacists in all categories (47/56 items). These results suggest that pharmacists must actively communicate to help others understand their specialty and build trusting relationships to improve patient care.

Small solid pseudopapillary tumor of the pancreas in a 32-year-old man: report of a case.

A solid pseudopapillary tumor (SPT) of the pancreas is a rare neoplasm that mainly occurs in young women. We herein report the case of a small SPT arising from the head of the pancreas in an asymptomatic 32-year-old man, plus a literature review of this tumor. A 32-year-old man was admitted to our department at Kumamoto University Hospital for the evaluation of a pancreatic mass. The tumor had central necrosis, which was poorly perfused on contrast-enhanced computed tomography (CT) and which had a high intensity on T2-weighted magnetic resonance imaging (MRI). Histology revealed the lesion to be a solid pseudopapillary tumor of the pancreas, with the characteristic pseudopapilla formation and central degeneration. However, no capsule formation was observed. The tumor was positive for CD56, CD10, alpha1-antitrypsin, alpha1-antichymotrypsin, beta-catenin, and progesterone receptor. However, the tumor was negative for pancreatic hormones, chromogranin-A, carcinoembryonic antigen, and carbohydrate antigen 19-9. We diagnosed the patient to have an SPT based on these histological findings. Small-sized solid pseudopapillary tumors of the pancreas are being increasingly recognized because of the recent advances in CT and MRI. We should also consider SPT even if it occurs in a male when the tumor contains necrosis-suspected areas which are poorly perfused on contrast-enhanced CT with a high intensity on T2-weighted MRI.

[Weekly paclitaxel therapy is curative for patients with retroperitoneal liposarcoma].

In March 2004, we resected a giant retroperitoneal liposarcoma and the transverse colon, spleen and left kidney in a 58-year-old woman. In July, recurrence was detected in the right pelvis and left upper abdomen; therefore, we resected the tumor. In September 2004, computed tomography (CT) revealed multiple recurrences in the right lower abdomen, left upper abdomen, front of the left lobe of the liver, and at the back of the stomach. In October 2004, we started mesna, doxorubicin, ifosfamide, and dacarbazine therapy (MAID); however, after 1 course, the disease progressed, and the patient developed edema in the bilateral legs due to inferior vena cava (IVC) compression. In November 2004, we started weekly paclitaxel therapy (100 mg/m(2), once a week for 3 weeks followed by 1 drug-free week). CT revealed no change as a result of chemotherapy; however, IVC compression had improved, and leg edema had decreased. In August 2005, chemotherapy was stopped; therefore,the patient's condition worsened. She died in September 2005. We performed weekly paclitaxel therapy for the patient with recurrent liposarcoma. This improved her symptoms and quality of life (QOL). Therefore,we consider weekly paclitaxel therapy to be effective for liposarcoma treatment.

Inhibition of DNA binding of Sox2 by the SUMO conjugation.

Sox2 is a member of the high mobility group (HMG) domain DNA-binding proteins for transcriptional control and chromatin architecture. The HMG domain of Sox2 binds the DNA to facilitate transactivation by the cooperative transcription factors such as Oct3/4. We report that mouse Sox2 is modified by SUMO at lysine 247. Substitution of the target lysine to arginine lost the sumoylation but little affected transcriptional potential or nuclear localization of Sox2. By contrast with the unmodified form, Sox2 fused to SUMO-1 did not augment transcription via the Fgf4 enhancer in the presence of Oct3/4. Further, SUMO-1-conjugated Sox2 at the lysine 247 or at the carboxyl terminus reduced the binding to the Fgf4 enhancer. These indicate that Sox2 sumoylation negatively regulates its transcriptional role through impairing the DNA binding.

Methylated DNA-binding domain 1 and methylpurine-DNA glycosylase link transcriptional repression and DNA repair in chromatin.

The methyl-CpG dinucleotide containing a symmetrical 5-methylcytosine (mC) is involved in gene regulation and genome stability. We report here that methylation-mediated transcriptional repressor methylated DNA-binding domain 1 (MBD1) interacts with methylpurine-DNA glycosylase (MPG), which excises damaged bases from substrate DNA. MPG itself actively represses transcription and has a synergistic effect on gene silencing together with MBD1. Chromatin immunoprecipitation analysis reveals the molecular movement of MBD1 and MPG in vivo: (i) The MBD1-MPG complex normally exists on the methylated gene promoter; (ii) treatment of cells with alkylating agent methylmethanesulfonate (MMS) induces the dissociation of MBD1 from the methylated promoter, and MPG is located on both methylated and unmethylated promoters; and (iii) after completion of the repair, the MBD1-MPG complex is restored on the methylated promoter. Mobility-shift and structural analyses show that the MBD of MBD1 binds a methyl-CpG pair (mCpG x mCpG) but not the methyl-CpG pair containing a single 7-methylguanine (N) (mCpG x mCpN) that is known as one of the major lesions caused by MMS. We further demonstrate that knockdown of MBD1 by specific small interfering RNAs significantly increases cell sensitivity to MMS. These data suggest that MBD1 cooperates with MPG for transcriptional repression and DNA repair. We hypothesize that MBD1 functions as a reservoir for MPG and senses the base damage in chromatin

Methyl-CpG binding domain 1 (MBD1) interacts with the Suv39h1-HP1 heterochromatic complex for DNA methylation-based transcriptional repression.

Cytosine methylation and posttranslational modifications of the amino termini of the core histones in the nucleosome provide epigenetic codes for genome regulation. In the nucleus, not only is the DNA methylated, but the methylated DNA is also interpreted by methyl-CpG binding domain (MBD) proteins. MBD1 possesses an MBD involved in mediating DNA methylation-dependent transcriptional repression. The MBD of MBD1 binds a symmetrically methylated CpG sequence, but the precise roles of this domain have not been investigated. In addition, little is understood about the state of histone modifications within MBD1-containing heterochromatin on methylated gene promoters. Here we show that histone H3 methylase Suv39h1 and the methyl lysine-binding protein HP1 directly interact with MBD of MBD1 in vitro and in cells. Suv39h1 was found to enhance MBD1-mediated transcriptional repression via MBD but not via the C-terminal transcriptional repression domain of MBD1. Furthermore, MBD1 links to histone deacetylases through Suv39h1, resulting in methylation and deacetylation of histones for gene inactivation. These data indicate that MBD1 may tether the Suv39h1-HP1 complex to methylated DNA regions, suggesting the presence of a pathway from DNA methylation to the modifications of histones for epigenetic gene regulation.