Alkaloids comprise one of the largest groups of plant secondary metabolites. Berberine, a benzylisoquinoline alkaloid, is preferentially accumulated in the rhizome of Coptis japonica, a ranunculaceous plant, whereas gene expression for berberine biosynthetic enzymes has been observed specifically in root tissues, which suggests that berberine synthesized in the root is transported to the rhizome, where there is high accumulation. We recently isolated a cDNA encoding a multidrug-resistance protein (MDR)-type ATP-binding cassette (ABC) transporter (Cjmdr1) from berberineproducing cultured C. japonica cells, which is highly expressed in the rhizome. Functional analysis of Cjmdr1 by using a Xenopus oocyte expression system showed that CjMDR1 transported berberine in an inward direction, resulting in a higher accumulation of berberine in Cjmdr1-injected oocytes than in the control. Typical inhibitors of ABC proteins, such as vanadate, nifedipine, and glibenclamide, as well as ATP depletion, clearly inhibited this CjMDR1-dependent berberine uptake, suggesting that CjMDR1 functioned as an ABC transporter. Conventional membrane separation methods showed that CjMDR1 was localized in the plasma membrane of C. japonica cells. In situ hybridization indicated that Cjmdr1 mRNA was expressed preferentially in xylem tissues of the rhizome. These findings strongly suggest that CjMDR1 is involved in the translocation of berberine from the root to the rhizome.

Community acquired-methicillin resistant Staphylococcus aureus (CA-MRSA) is a socially problematic pathogen that infects healthy individuals, causing severe disease. CA-MRSA is more virulent than hospital associated-MRSA (HA-MRSA). The underlying mechanism for the high virulence of CA-MRSA is not known. The transcription product of the psm-mec gene, located in the mobile genetic element SCCmec of HA-MRSA, but not CA-MRSA, suppresses the expression of phenol-soluble modulin α (PSMα), a cytolytic toxin of S. aureus. Here we report that psm-mec RNA inhibits translation of the agrA gene encoding a positive transcription factor for the PSMα gene via specific binding to agrA mRNA. Furthermore, 25% of 325 clinical MRSA isolates had a mutation in the psm-mec promoter that attenuated transcription, and 9% of the strains had no psm-mec. In most of these psm-mec-mutated or psm-mec-deleted HA-MRSAs, PSMα expression was increased compared with strains carrying intact psm-mec, and some mutated strains produced high amounts of PSMα comparable with that of CA-MRSA. Deletion of psm-mec from HA-MRSA strains carrying intact psm-mec increased the expression of AgrA protein and PSMα, and virulence in mice. Thus, psm-mec RNA suppresses MRSA virulence via inhibition of agrA translation and the absence of psm-mec function in CA-MRSA causes its high virulence property.

We analyzed 81 ovarian cancers for loss of heterozygosity (LOH) on 10q23 and for mutations in PTEN. LOH was common among the endometrioid (43%) and serous (28%) cancers, but was infrequent among the other histological subtypes. Somatic PTEN mutations were detected in seven (21%) endometrioid cancers and the mutation in all informative cases was accompanied by loss of the wild-type allele. One mucinous cancer without 10q23 LOH was shown to harbor two somatic PTEN mutations. Frequent LOH was observed on chromosome 6q (60.0%) and chromosome 10q (40.0%) in ovarian atypical endometriosis, but no PTEN mutations were observed. These findings support the hypothesis that endometrioid and clear cell ovarian carcinomas may arise through malignant transformation of endometriotic lesions.

The presence of vascular invasion is a reliable prognostic indicator. Recording of tumor recurrence pattern may lead to a better selection of patients for adjuvant systemic therapy after surgery.

Umbilical endometriosis is a very rare condition, and as far as we are aware, there have been no reported cases of its malignant transformation. Here, we report a case of clear cell adenocarcinoma arising from umbilical endometriosis in a 60-year-old woman who underwent hysterectomy for a uterine myoma at the age of 38, and who denied cyclic bleeding at the site of an umbilical cutaneous nodule correlating with menses until the age of 48. An umbilical tumor (3 cm diameter) was identified by magnetic resonance imaging and an abnormal accumulation was found only at the umbilical lesion by positron emission tomography examination. We observed endometriosis adjacent to the clear cell adenocarcinoma and transformation to carcinoma from endometriosis at the umbilical lesion histopathologically. Clear cell adenocarcinoma of the umbilicus was thought to have arisen from endometriosis; it expressed HER-2 protein and showed strong mesothelial characteristics immunohistochemically.