Severe Asherman's syndrome complicated with placenta increta conceived by intracytoplasmic sperm injection following hysteroscopic surgery.

Although severe Asherman's syndrome is a disease that may cause infertility, pregnancy and childbirth are possible by performing hysteroscopic surgery. However, the obstetrical outcome is not always satisfactory. We report a case where severe Asherman's syndrome occurred following a cesarean section. Hysteroscopic surgery was performed due to secondary infertility, and pregnancy was achieved through a subsequent intracytoplasmic sperm injection. At 23 weeks of gestation, the patient was hospitalized due to the threat of premature labor, and a cesarean section was performed at 29 weeks of gestation after pregnancy-induced hypertension occurred. It was determined to be abnormal adherent placentation such as placenta increta through intraoperative findings, and a cesarean hysterectomy was performed. The pathological diagnosis of the uterus was placenta increta. Due to the risk of complications from placenta increta in pregnancies following hysteroscopic surgery in patients with severe Asherman's syndrome, it is important to realize the high risk involved in such cases during the pregnancy course, and careful perinatal management should be required.

Trends in the incidence of uterine cancer in Niigata, Japan: a population-based study from 1982 to 2007.

This study investigated trends in the incidence of uterine cancer in Japan. Data from the Gynecological Cancer Registry of Niigata comprising all new cases of uterine cancer registered for the entire female population aged 15 years and over a 25-year period were examined. The age-standardized ratio of carcinoma in situ has substantially increased among females < 40 years of age (from 3.8 (in the period of 1982-1989) to 40.9 (2000-2007). There was a significant trend in increasing incidence of invasive cervical cancer for those < 40 years of age (from 4.7 to 13.1), whereas a significant trend of decreasing incidence for the 50+ year age group. The ratios of corpus cancer were increased approximately two-folds both among the population aged < 50 years and those aged 50+ years and thus becoming equivalent to invasive cervical cancer. This prefecture-wide population-based study shows the practical trend in uterine cancer in Japanese females. The current health service must emphasize education among young adults concerning cervical cancer prevention while concentrating on screening. Avoiding risk factors, such as obesity, and increasing protective factors may lower risk for corpus cancer both in younger and older females.

Humanizing bone marrow in immune-deficient mice.

Humanized mice are useful for studying human hematopoietic stem cells (HSCs) and their niche. In particular, clonal study of human HSC enables precise comparison of in vivo behavior between murine and human HSCs. A single HSC is able to reconstitute hematopoiesis even after serial transplantations in mice. While the life span of somatic cells is over that of individual in mice, this is not the case in humans. Clonal studies of human HSCs clearly demonstrated their aging in hosts. Since murine studies have demonstrated that HSCs are protected from aging by their niche in bone marrow, the humanizing niche model will reveal the precise mechanism by which human HSCs are protected from exhaustion in vivo. Direct transplantation of human mesenchymal stem cells into mouse bone marrow results in reconstitution of the functional human hematopoietic microenvironment comprised of pericytes, myofibroblasts, reticular cells, osteocytes in bone, bone-lining osteoblasts, and endothelial cells. These humanized mouse models are essential for testing whether the insights on hematopoiesis from mouse studies are applicable to humans before clinical application.

Primary retroperitoneal mucinous cystadenocarcinoma associated with pregnancy.

Primary retroperitoneal mucinous cystadenocarcinoma (PRMC) is an extremely rare tumor. Only 30 cases have been reported previously in the English literature, and little information is available concerning its treatment and prognosis. The patient was a 28-year-old woman, presenting with a right mid-abdominal tumor at 26 weeks of gestation. At 31 weeks of gestation, she underwent an exploratory laparotomy and was diagnosed with a PRMC. No disseminated tumor was observed, and an excision of only the tumor was performed. She had an uneventful vaginal delivery at 38 weeks of gestation and remains free of disease at 13 months after the operation. This report describes a case of PRMC associated with pregnancy. The optimal management of these retroperitoneal masses during pregnancy is discussed. Based on limited experience and the current literature, a PRMC with an intact capsule and no dissemination appears to have a good prognosis and can be treated by tumor excision alone in patients who wish to preserve fertility.

Prediction of myometrial invasion in patients with endometrial carcinoma: comparison of magnetic resonance imaging, transvaginal ultrasonography, and gross visual inspection.

This study evaluated the accuracy of magnetic resonance imaging (MRI) and transvaginal ultrasonography (TVUS) in preoperative detection of myometrial invasion by endometrial cancer. We also evaluated the results of gross visual inspection (GVI) of surgical specimens compared with histopathological diagnosis. One hundred and seventy-seven women underwent preoperative pelvic MRI, TVUS, and intraoperative GVI. Myometrial tumor invasion was evaluated histologically and classified as absent (depth a), superficial (depth b: < or = 50% invasion), or deep (depth c: > 50% invasion). The accuracy of MRI, TVUS, and GVI were 64.0, 66.9, and 63.8%, respectively. The positive predictive values of of each modality for depth a were 52.6, 51.4, and 52.2%, respectively. The accuracy of each in detecting deep myometrial invasion (depth c) were 84.0, 86.9, 83.1%. Although evaluation of depth a was limited with all modalities, MRI and TVUS were shown to be reliable for preoperative evaluation of deep myometrial invasion. The high accuracy of these three methods suggests that they are useful either interchangeably or in combination.

Radiation myelopathy after radioactive iodine therapy for spine metastasis.

A case of radiation myelopathy after radioactive iodine therapy is reported. This is the first report to describe radiation myelopathy after I-131 therapy. A 62-year-old female with spinal metastasis of T10 received I-131 therapy. She presented with radiation myelopathy 34 months after the irradiation. We need to recognize the possibility of this serious complication even in the case of I-131 therapy. There is a risk of radiation myelopathy even after I-131 therapy, especially in cases with spinal cord compression such as this.

Expression of CD90 on keratinocyte stem/progenitor cells.

BACKGROUND: The identification and purification of keratinocyte stem cells (KSCs) that are capable of self-renewal and maintenance of differentiating cell populations could contribute both to our understanding of the biology of these cells, and to significant clinical applications, such as the culturing of keratinocytes for transplantation to severe burn wounds. Here, we report the detection of CD90(+) cells in cultured normal human epidermal keratinocytes and adult skin. OBJECTIVES: To investigate the biological function of CD90(+) and CD90(-) keratinocytes. METHODS: CD90(+) and CD90(-) keratinocytes were purified from adult skin and cultured keratinocytes using fluorescent activated cell sorting, and their biological abilities were analysed using both in vitro and in vivo assays. RESULTS: Flow cytometry (FCM) analysis identified approximately 18% of post-primary neonatal keratinocytes as CD90(+). However, during expansion of the culture, the expression level of CD90 rapidly decreased to about 2.5% at passage 10, while most of the keratinocytes maintained expression of alpha6 integrin. Purified CD90(+) keratinocytes demonstrated a sixfold higher cell growth rate than CD90(-) cells and the ability to form large (over 3 mm in diameter) colonies. We then quantitatively evaluated both populations using a previously described in vivo human epidermal cyst formation assay. Enhanced green fluorescent protein (EGFP)-labelled CD90(+) or CD90(-) keratinocytes were subcutaneously injected into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Six weeks after transplantation, EGFP(+) cell clusters in human epidermal cysts were evaluated using image analysis software. EGFP(+) cell cluster areas in the basal layer, derived from EGFP(+) CD90(+) cells, were eightfold larger than clusters of EGFP(+) CD90(-) cells. Furthermore, immunohistochemical staining and FCM analysis indicated that CD90 was expressed in most of the basal layer of the normal human epidermis. CONCLUSIONS: These results indicated that CD90 is a useful marker for the detection of human KSC-enriched populations in cultured human keratinocytes.

Long-term conservative therapy for endometrial adenocarcinoma in young women.

BACKGROUND: To evaluate the efficacy and safety of long-term conservative therapy with medroxyprogesterone acetate (MPA) for endometrial carcinoma in young patients who had experienced failure after initial therapy or relapse, we reviewed the clinical and pathologic records of eight patients diagnosed with well-differentiated endometrial adenocarcinoma without myometrial invasion who were treated with MPA for over 6 months because of treatment failure or relapse. RESULTS: The average duration of MPA treatment was 22 months. All patients were followed-up for a mean of 76.5 months. Seven patients responded to initial MPA treatment within a period of 14 months (mean, 7.9 months). All these patients experienced relapse and the mean time to relapse was 11.6 months (range, 4-33 months). All six patients with relapse were treated with additional treatments of MPA, and all but one responded to this treatment within a period of 16 months (mean, 8.0 months). Six patients ultimately underwent hysterectomy. All presented well-differentiated endometrioid adenocarcinomas without extrauterine disease. Three became pregnant and two delivered full-term normal infants. No patient died of the disease. CONCLUSION: Although lesions are expected to disappear with prolonged MPA treatment, this form of progestin therapy is hazardous because recurrence occurs frequently. Only strictly selected patients should therefore be indicated for long-term MPA treatment and careful evaluation before and after treatment should be performed.

Complete response to docetaxel and carboplatin combination chemotherapy for a stage IV uterine papillary serous carcinoma: a case report.

We report a case of a stage IV uterine papillary serous carcinoma (UPSC) with multiple organ metastases. The patient was treated with docetaxel and carboplatin combination chemotherapy. After five courses, uterine tumor, Douglas tumor, lymphadenopathy, and distant metastases on magnetic resonance imaging or computed tomography scan were completely resoluted. Moreover, endometrial biopsy showed no carcinoma tissues after six courses. We suggest that this regimen may be effective for treatment of advanced-stage UPSC.

Placental site trophoblastic tumor presenting as subaponeurotic metastasis.

Cases of metastatic placental site trophoblastic tumor (PSTT) have a very poor prognosis because these tumors tend to be less sensitive to chemotherapy than other types of gestational trophoblastic disease. We describe the case of a 25-year-old woman who presented with occipital tumor and abnormal vaginal bleeding. Hysterectomy, bilateral salpingo-oophorectomy, and occipital tumor removal revealed a primary PSTT in the uterus, with ovarian and occipital subaponeurotic metastases. She received etoposide, methotrexate, actinomycin-D/cyclophosphamide, vincristine chemotherapy and had a complete clinical remission. Fifteen months later, she had a recurrent subaponeurotic occipital tumor invading the cranium and underwent tumor removal along with cranial bone followed by local irradiation. She was then treated with etoposide, cis-platinum/etoposide, methotrexate, actinomycin-D chemotherapy and again had a remission for 5 months. The patient, however, had a left parietal subaponeurotic tumor, invading the dura mater, and received local irradiation. Soon after, she developed left orbital bone metastasis, treated by local irradiation. These bone metastases responded to the radiation completely. However, multiple organ metastases were found, and she died of the disease. This represents the first case of PSTT with initial subaponeurotic metastasis in a living patient. New modalities of treatment for high-risk or metastatic PSTT need to be developed.

Association between single nucleotide polymorphisms of estrogen receptor alpha gene and efficacy of HRT on bone mineral density in post-menopausal Japanese women.

BACKGROUND: Although HRT for post-menopausal women can protect against bone loss, variations in bone responses exist. We studied whether single nucleotide polymorphisms (SNP) of the estrogen receptor-alpha (ERalpha) gene contribute to the effect of HRT on lumbar spine bone mineral density (BMD). METHODS: Subjects were 84 post-menopausal women who had been taking HRT for 3 years to treat osteopenia or osteoporosis. Eighteen SNP in the ERalpha gene were characterized by a single nucleotide primer extension assay. RESULTS: Genotyping of the 84 individuals revealed that all SNP were quite common, the minor allele frequency being > or = 20%. A SNP in intron 6 (IVS6+14144) was significantly associated with the response to HRT for the first 3 years after starting treatment (P = 0.043, 0.025 and 0.032 for the first, second and third years respectively). Haplotype analysis revealed that a combination of SNP IVS6+14144 and IVS4+4238 was significantly correlated with the response to HRT; women with haplotype G-G (IVS6 14144-IVS4 4238) showed a significantly higher response (P = 0.014, 0.043 and 0.010 for the first second and third year respectively). CONCLUSIONS: These results suggest that a specific SNP and the haplotype of the selected SNP could be used to predict the effect of HRT on lumbar BMD.

Cytoplasmic and mitochondrial Ca levels in brown adipocytes.

AIM: We elucidated the mitochondrial functions of brown adipocytes in intracellular signalling, paying attention to mitochondrial activity and noradrenaline- and forskolin-induced Ca(2+) mobilizations in cold-acclimated rats. METHODS: A confocal laser-scanning microscope of brown adipocytes from warm- or cold-acclimated rats was employed using probes rhodamine 123 which is a mitochondria-specific cationic dye, and the cytoplasmic and mitochondrial Ca(2+) probes fluo-3 and rhod-2. X-ray microanalysis was also studied. RESULTS: The signal of rhodamine 123 in the cells was decreased by antimycin A which effect was less in cold-acclimated cells than warm-acclimated cells. Cytoplasmic and mitochondrial Ca(2+) in cold-acclimated brown adipocytes double-loaded with fluo-3 and rhod-2 were measured. Noradrenaline induced the rise in cytoplasmic Ca(2+) ([Ca(2+)](cyto)) followed by mitochondrial Ca(2+) ([Ca(2+)](mito)), the effect being transformed into an increase in [Ca(2+)](cyto) whereas a decrease in [Ca(2+)](mito) by antimycin A or carbonyl cyanide m-chlorophenylhydrazone (CCCP). Antimycin A induced small Ca(2+) release from mitochondria. CCCP induced Ca(2+) release from mitochondria only after the cells were stimulated with noradrenaline. Further, forskolin also elicited an elevation in [Ca(2+)](cyto) followed by [Ca(2+)](mito) in the cells. The Ca measured by X-ray microanalysis was higher both in the cytoplasm and mitochondria whereas K was higher in the mitochondria of cold-acclimated cells in comparison to warm-acclimated cells. CONCLUSIONS: These results suggest that noradrenaline and forskolin evoked an elevation in [Ca(2+)](cyto) followed by [Ca(2+)](mito), in which H(+) gradient across the inner membrane is responsible for the accumulation of calcium on mitochondria. Moreover, cAMP also plays a role in intracellular and mitochondrial Ca(2+) signalling in cold-acclimated brown adipocytes.

Selective coactivation of estrogen-dependent transcription by CITED1 CBP/p300-binding protein.

CITED1, a CBP/p300-binding nuclear protein that does not bind directly to DNA, is a transcriptional coregulator. Here, we show evidence that CITED1 functions as a selective coactivator for estrogen-dependent transcription. When transfected, CITED1 enhanced transcriptional activation by the ligand-binding/AF2 domain of both estrogen receptor-alpha (ERalpha) and ERbeta in an estrogen-dependent manner, but it affected transcriptional activities of other nuclear receptors only marginally. CITED1 bound directly to ERalpha in an estrogen-dependent manner through its transactivating domain, and this binding activity was separable from its p300-binding activity. CITED1 was strongly expressed in nulliparous mouse mammary epithelial cells and, when expressed in ER-positive MCF-7 breast cancer cells by transduction, exogenous CITED1 enhanced sensitivity of MCF-7 cells to estrogen, stabilizing the estrogen-dependent interaction between p300 and ERalpha. The estrogen-induced expression of the transforming growth factor-alpha (TGF-alpha) mRNA transcript was enhanced in the CITED1-expressing MCF-7 cells, whereas estrogen-induced expression of the mRNA transcripts for progesterone receptor or pS2 was not affected. Chromatin immunoprecipitation assay revealed that endogenous CITED1 is recruited to the chromosomal TGF-alpha promoter in MCF-7 cells in an estrogen-dependent manner but not to the pS2 promoter. These results suggest that CITED1 may play roles in regulation of estrogen sensitivity in a gene-specific manner.

The interface between innate and acquired immunity: glycolipid antigen presentation by CD1d-expressing dendritic cells to NKT cells induces the differentiation of antigen-specific cytotoxic T lymphocytes.

In vivo administration of NKT cell ligand, alpha-galactosylceramide (alpha-GalCer), caused the activation of NKT cells to induce a strong NK activity and cytokine production by CD1d-restricted mechanisms. Surprisingly, we also found that alpha-GalCer induced the activation of immunoregulatory cells involved in acquired immunity. Specifically, in vivo administration of alpha-GalCer resulted in the induction of the early activation marker CD69 on CD4(+) T cells, CD8(+) T cells and B cells in addition to macrophages and NKT cells. However, no significant induction of CD69 was observed on cells from CD1d- or V(alpha)14 NKT-deficient mice, indicating an essential role for the interaction between NKT cells and CD1d-expressing dendritic cells (DC) in the activation of acquired immunity in response to alpha-GalCer. Indeed, in vivo injection of alpha-GalCer resulted not only in the activation of NKT cells but also in the generation of CD69(+)CD8(+) T cells possessing both cytotoxic T lymphocyte (CTL) activity and IFN-gamma-producing ability. Tumor-specific CTL generation was also accelerated by alpha-GalCer. The critical role of CD40-CD40 ligand (CD40L)-mediated NKT-DC interaction during the development of CD69(+)CD8(+) CTL by alpha-GalCer was demonstrated by blocking experiments using anti-CD40L mAb. These findings provide direct evidence for a critical role of CD1d-restricted NKT cells and DC in bridging innate and acquired immunity.

A green fluorescent protein-reporter mammalian two-hybrid system with extrachromosomal maintenance of a prey expression plasmid: application to interaction screening.

An improved mammalian two-hybrid system designed for interaction trap screening is described in this paper. CV-1/EBNA-1 monkey kidney epithelial cells expressing Epstein-Barr virus nuclear antigen 1 (EBNA-1) were stably transfected with a reporter plasmid for GAL4-dependent expression of the green fluorescent protein (GFP). A resulting clone, GB133, expressed GFP strongly when transfected transiently with transcriptional activators fused to GAL4 DNA-binding domain with minimal background GFP expression. GB133 cells maintained plasmids containing the OriP Epstein-Barr virus replication origin that directs replication of plasmids in mammalian cells in the presence of the EBNA-1 protein. GB133 cells transfected stably with a model bait expressed GFP when further transfected transiently with an expression plasmid for a known positive prey. When the bait-expressing GB133 cells were transfected transiently with an OriP-containing expression plasmid for the positive prey together with excess amounts of empty vector, cells that received the positive prey were readily identified by green fluorescence in cell culture and eventually formed green fluorescent microcolonies, because the prey plasmid was maintained by the EBNA-1/Ori-P system. The green fluorescent microcolonies were harvested directly from the culture dishes under a fluorescence microscope, and total DNA was then prepared. Prey-encoding cDNA was recovered by PCR using primers annealing to the vector sequences flanking the insert-cloning site. This system should be useful in mammalian cells for efficient screening of cDNA libraries by two-hybrid interaction.

Interleukin-4-dependent induction of preproenkephalin in antigen-specific T helper-type 2 (Th2) cells.

Naive Th cells obtained from OVA(323-339)-specific DO11.10 TCR-Tg mice did not express preproenkephalin (PPE) mRNA. However, culture of naive Th cells with OVA(323-339) peptide (OVA-pep) plus IL-2 under Th2-inducing conditions for 7 days resulted in an induction of PPE mRNA. The PPE mRNA was also induced by culturing with OVA-pep plus IL-2 (neutral condition). However, PPE mRNA induction under neutral conditions was totally abrogated by addition of anti-IL-4 mAb. The existence of methionine-enkephalin was also demonstrated in peptidase-digested peptides derived from Th2 cell lysate. These results demonstrate that IL-4 is a critical factor for the induction of PPE mRNA in freshly expanded antigen-specific Th2 cells.

[Right tracheal bronchus with anomalous ramification of the bronchial artery disclosed during an episode of hemoptysis].

A 63-year-old woman was referred to our hospital on June 18th, 1998 during an episode of hemoptysis that had lasted for 6 days. She had no hemorrhagic diathesis and no history of pulmonary disease. Chest X-ray films disclosed a ground-glass opacity in the right upper lung field. Bronchoscopic examination revealed bleeding from an anomalous ectopic orifice on the right lateral trachea, about 1 cm above the carina. Chest computed tomographic examinations by conventional and spiral methods readily disclosed an ectopic bronchus. Bronchial arteriography showed that the tracheal bronchus was fed by a branched vessel of the thyrocervical artery arising from the brachiocephalic artery. Atypical mycobacterium was detected in bronchoalveolar lavage fluid from the ectopic bronchus. A shunt had formed with the pulmonary artery and peripheral parts of the bronchial artery that fed the tracheal bronchus. It was speculated that the hemoptysis in this case might be due to the combined phenomena of infection and abnormal vessel formation in the tracheal bronchus. In our patient, the system of blood supply to the tracheal bronchus may have been a manifestation of atavism because it closely resembled the circulatory structure of the tracheal bronchi normally observed in sheep and giraffes. The tracheal bronchus should be taken into consideration as a potential cause of hemoptysis, inflammatory changes, and atelectasis during intubation.

Molecular cloning of a novel type 1 cytokine receptor similar to the common gamma chain.

In a complementary DNA (cDNA) screening of murine Th2-skewed lymphocytes with our recently developed signal sequence trap method termed SST-REX, a novel type 1 cytokine receptor, Delta1 (delta1), was identified. Although delta1 is ubiquitously expressed in multiple tissues, the expression level is higher in Th2-skewed lymphocytes than in Th1-skewed ones. The delta1 cDNA encodes a 359-amino acid type 1 membrane protein. The extracellular domain of 206 amino acids showed 24% identity with the murine common gamma receptor that is shared among the receptors for interleukin(IL)-2, IL-4, IL-7, IL-9, and IL-15. The membrane-proximal region of delta1 includes a box1 motif, which is important for association with Janus kinases (JAKs), and showed a significant homology with that of the mouse erythropoietin receptor (EPOR). A box2 motif was also found in close proximity to the box1 region. Dimerization of the cytoplasmic region of delta1 alone did not transduce proliferative signals in IL-3-dependent cell lines. However, the membrane-proximal region of delta1 could substitute for that of human EPOR in transmitting proliferative signals and activating JAK2. These results suggest that delta1 is a subunit of cytokine receptor that may be involved in multiple receptor systems and play a regulatory role in the immune system and hematopoiesis.