Ovarian hyperstimulation syndrome following surgical removal of a complete hydatidiform mole: a case report.

BACKGROUND: Generally, ovarian hyperstimulation syndrome develops after superovulation caused by ovulation-inducing drugs in infertile patients. However, ovarian hyperstimulation syndrome associated with natural pregnancy is rare, and most cases of ovarian hyperstimulation syndrome have been associated with a hydatidiform mole. CASE PRESENTATION: We describe a case of a 16-year-old Japanese girl with a complete hydatidiform mole. The patient was referred for intensive examination and treatment of the hydatidiform mole and underwent surgical removal of the hydatidiform mole at 9 weeks, 5 days of gestation. Histopathological examination revealed a complete hydatidiform mole. The patient's blood human chorionic gonadotropin level decreased from 980,823 IU/L to 44,815 IU/L on postoperative day 4, and it was below the cutoff level on postoperative day 64. Transvaginal ultrasonography on postoperative day 7 revealed a multilocular cyst measuring 82 × 43 mm in the right ovary and a multilocular cyst measuring 66 × 50 mm in the left ovary. Both ovarian cysts enlarged further. Magnetic resonance imaging on postoperative day 24 revealed that the right multilocular ovarian cyst had enlarged to 10 × 12 cm and that the left multilocular ovarian cyst had enlarged to 25 × 11 cm. Blood examination showed an elevated estradiol level as high as 3482 pg/ml. We diagnosed the patient with bilateral giant multilocular cysts accompanied by ovarian hyperstimulation syndrome because of the rapid increase in the size of the cysts. The patient complained of mild abdominal bloating; however, symptoms such as nausea, vomiting, dyspnea, and abdominal pain were not observed. Therefore, we chose spontaneous observation in the outpatient clinic. The cysts gradually decreased and disappeared on postoperative day 242. CONCLUSION: Physicians should be aware that ovarian cysts can occur and can increase rapidly after abortion of a hydatidiform mole. However, the ovarian cyst can return to its original size spontaneously even if it becomes huge.

Laparoscopic splenectomy for solitary splenic metastasis in a patient with ovarian cancer with a long disease-free interval: a case report.

BACKGROUND: In general, splenic metastasis of epithelial ovarian cancer is considered a terminal stage resulting in widespread metastasis. Solitary splenic metastasis of epithelial ovarian cancer is rare in patients with post-treatment ovarian cancer with long disease-free intervals. CASE PRESENTATION: We report a case of a 62-year-old Japanese woman who presented with elevated serum cancer antigen 125 due to a solitary splenic metastasis of ovarian cancer. She underwent primary open cytoreduction including resection of the right ovarian cancer and postoperative chemotherapy, followed by secondary open cytoreduction and additional postoperative chemotherapy. The disease-free interval was more than 5 years after the additional postoperative chemotherapy. She did not complain of any symptoms and there were no abnormal findings except for elevated cancer antigen 125. However, computed tomography and magnetic resonance imaging revealed a tumor of 6.5 × 4.5 cm in her spleen, and 18F-fluorodeoxyglucose positron emission tomography-computed tomography showed no other metastatic lesions. Laparoscopic splenectomy was performed as tertiary cytoreduction with a diagnosis of a solitary splenic metastasis. Her elevated cancer antigen 125 immediately decreased to within the normal range after the splenectomy. On microscopic examination, the tumor was grade 3 endometrioid adenocarcinoma localized in the spleen, consistent with the previous grade 3 endometrioid adenocarcinoma ovarian cancer. CONCLUSIONS: Elevated cancer antigen 125 is useful for early detection of metastasis of ovarian cancer. Computed tomography, magnetic resonance imaging, and 18F-fluorodeoxyglucose positron emission tomography-computed tomography are useful to evaluate whether splenic metastasis of ovarian cancer is solitary, and laparoscopic splenectomy is safe and feasible for a solitary splenic metastasis.

Effect of hepatocyte growth factor on long term hematopoiesis of human progenitor cells in transgenic-severe combined immunodeficiency mice.

Hepatocyte growth factor (HGF), which was originally isolated as a liver generating factor, enhances hematopoiesis. To study the effect of HGF on hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs), we generated severe combined immunodeficiency (SCID) mice producing human (h) HGF and/or stem cell factor (SCF) by transferring the relevant genes to fertilized eggs, and then transplanted hematopoietic progenitors from human cord blood into the transgenic (Tg) SCID mice. Six months after transplantation, a significantly larger number of human cells were found in the Tg SCID mice than in non-Tg controls. Characteristically, the recipient SCID mice producing h HGF (HGF-SCID) had a significantly increased number of h CD41+ cells, whereas the SCF-SCID recipients had more CD11b+ cells. Significantly large numbers of CD34+ progenitors were found in the SCID mice transferred with both h HGF and h SCF genes (HGF/SCF-SCID) when compared with HGF-SCID or SCF-SCID mice. These results imply that HGF supports the differentiation of progenitors in megakaryocyte lineage, whereas SCF supports that in myeloid lineage. The results also imply that HGF acts on HSCs/HPCs as a synergistic proliferative factor combined with SCF. We have demonstrated the advantage of the human cytokine-producing animal in the maintenance of human HSCs.

Expression of the endothelial cell differentiation gene 7 (EDG-7), a lysophosphatidic acid receptor, in ovarian tumor.

AIM: Lysophosphatidic acid (LPA) has received attention as a mitogen because the physiologically active lipid stimulates ovarian cancer cell growth by interacting with specific receptors, the endothelial cell differentiation gene (EDG) family. In the present study, we have investigated the expression of EDG-7 mRNA, part of the EDG family, in both human ovarian cancers and established human ovarian cancer cell lines. METHODS: RNA was extracted from six ovarian cancer cell lines and multiple cancerous and normal ovarian tissues. The expression of EDG-7 mRNA was measured using reverse transcription-polymerase chain reaction and northern blotting, using reduced glyceraldehyde-phosphate dehydrogenase and S26 as internal controls. RESULTS: Of the cell lines tested, EDG-7 mRNA was expressed most intensely in CRL-11731 and CRL-1572 and at a lesser but still substantial level in CRL-11732. The expression of EDG-7 mRNA was limited in MCAS, CRL-11730 and TYKnu. In the ovarian cancer tissues, EDG-7 mRNA was expressed most highly in endometrioid adenocarcinoma and serous cystadenocarcinoma. The expression of EDG-7 mRNA was limited in clear cell adenocarcinoma and undetectable in mucinous cystadenocarcinoma. CONCLUSIONS: The intense EDG-7 expression in ovarian cancers suggests that the relation between LPA and EDG-7 (an LPA receptor) is involved in cancer cell growth and proliferation in some histologic subtypes of ovarian cancer.

Enhancement of allogeneic hematopoietic stem cell engraftment and prevention of GVHD by intra-bone marrow bone marrow transplantation plus donor lymphocyte infusion.

We examined the effect of intra-bone marrow (IBM)-bone marrow transplantation (BMT) in conjunction with donor lymphocyte infusion (DLI) on the engraftment of allogeneic bone marrow cells (BMCs) in mice. Recipients that had received 6 Gy of radiation completely rejected donor BMCs, even when IBM-BMT was carried out. However, when BMCs were IBM injected and donor peripheral blood mononuclear cells (PBMNCs) were simultaneously injected intravenously (DLI), donor cell engraftment was observed 7 days after BMT and complete donor chimerism continued thereafter. It is of interest that the cells of recipient origin did not recover, and that the hematolymphoid cells, including progenitor cells (Lin-/c-kit+ cells) in the recipients, were fully reconstituted with cells of donor origin. The cells in the PBMNCs responsible for the donor BMC engraftment were CD8+. Recipients that had received 6 Gy of radiation, IBM-BMT, and DLI showed only a slight loss of body weight, due to radiation side effects, and had no macroscopic or microscopic symptoms of graft-versus-host disease. These findings suggest that IBM-BMT in conjunction with DLI will be a valuable strategy for allogeneic BMT in humans.

Plasmacytoid dendritic cells regulate Th cell responses through OX40 ligand and type I IFNs.

Dendritic cells (DCs) show a functional plasticity in determining Th responses depending on their maturational stage or on maturational signals delivered to the DCs. Human plasmacytoid DCs (PDCs) can induce either Th1- or Th2-type immune responses upon exposure to viruses or IL-3, respectively. In this study we have investigated the Th-polarizing capacity of PDCs after short (24-h) or long (72-h) culture with stimuli and have assessed the expression and function of OX40 ligand (OX40L) in PDC-mediated Th polarization in addition to type I IFN-dependent responses. IL-3-treated PDCs expressed OX40L, but produced almost no IFN-alpha in response to T cell stimulation (CD40 ligand or T cell interaction), resulting in the preferential priming of Th2 cells through OX40L-dependent mechanisms. Meanwhile, PDCs were rapidly endowed by viral infection (Sendai virus) with a high potency to develop IFN-gamma-producing Th cells depending on their capacity to residually produce IFN-alpha. Although Sendai virus-stimulated PDCs simultaneously expressed OX40L in their maturational process, the Th1-inducing effect of endogenous type I IFNs may overcome and thus conceal the OX40L-dependent Th2 responses. However, during maturation in response to Sendai virus over the longer 72-h period, the expression level of OX40L was up-regulated, whereas the residual IFN-alpha-producing ability was down-regulated, and consequently, the PDCs with prolonged Sendai virus stimulation induced Th2 responses to some extent. Thus, PDCs have the distinct means to dictate an appropriate response to environmental stimuli.

Expression of 20alpha-hydroxysteroid dehydrogenase mRNA in human endometrium and decidua.

Progesterone secreted from ovarian corpus luteum plays pivotal roles in endometrial differentiation, and local progesterone metabolism to regulate its concentration in endometrial tissues is essential for the successful implantation and maintenance of pregnancy. In this study, we evaluated the expression of mRNA for 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD), a key enzyme which converts progesterone to a biologically inactive metabolite, in human endometrial tissues and cultured endometrial stromal cells as well as decidua and chorionic tissues of early pregnancy. The level of 20alpha-HSD mRNA expression in secretory phase endometrium was significantly higher than that in proliferative phase endometrium and chorionic tissues. The expression level in decidual tissue was also significantly higher than that in chorionic tissue. In cultured endometrial stromal cells, 20alpha-HSD mRNA expression was slightly enhanced at a lower progesterone concentration of 0.01 micromol/l, and an increase in its expression was significantly suppressed at higher concentrations of 1 micromol/l or greater. No effect on the gene expression was seen in cultured endometrial stromal cells with various concentrations of 17beta-estradiol. These results suggest that progesterone itself contributes to the regulation of local progesterone concentration through 20alpha-HSD levels in endometrial stromal cells at peri-implantation periods.

Smoking enhances oxytocin-induced rhythmic myometrial contraction.

Although smoking during pregnancy is one of the major risk factors of premature delivery, the underlying mechanism by which smoking causes premature delivery is unknown. In the present study, we examined the effects of smoking on uterine contractility induced by oxytocin and prostaglandin F(2alpha). Rats inhaled either cigarette smoke or room air from Day 14 to Day 16 of pregnancy through an inhalation apparatus for experimental animals (type "Hamburg II"). After the rats were killed on Day 17 of pregnancy, the uterine contractile sensitivity and activity on exposure to oxytocin or prostaglandin F2alpha were investigated. The expression levels of oxytocin-receptor mRNA and prostaglandin F(2alpha) receptor mRNA in the uterus were investigated by reverse transcription-polymerase chain reaction. The contractile activity was assessed as the contractile force and the frequency of rhythmic contractions of myometrial strips that were treated with oxytocin or prostaglandin F(2alpha). The contractile sensitivity to oxytocin was significantly higher in the smoking group than in the control group (P < 0.01). Although the contractile force of oxytocin-induced contractions did not differ between the smoking and control groups, the frequency of contractions was significantly higher in the smoking group than in the control group (P < 0.01). On the other hand, no significant differences were found in the contractile sensitivity and activity in response to prostaglandin F(2alpha) between the smoking and control groups. The expression of oxytocin-receptor mRNA in the myometrium was significantly increased in the smoking group compared with the control group (P < 0.01). However, no significant difference was found in the level of expression of prostaglandin F(2alpha)-receptor mRNA between the two groups. These results suggest that smoking during pregnancy increases the contractile sensitivity and activity of the myometrium in response to oxytocin by up-regulating the expression of oxytocin-receptor mRNA. The effects of smoking on the contractile sensitivity and activity of the myometrium in response to oxytocin may increase the risk of premature delivery in smokers.

Comparison of bone marrow cells harvested from various bones of cynomolgus monkeys at various ages by perfusion or aspiration methods: a preclinical study for human BMT.

Using cynomolgus monkeys, we have previously established a new method for harvesting bone marrow cells (BMCs) with minimal contamination of the BMCs with T cells from the peripheral blood. We originally conducted this new "perfusion method" in the long bones (the humerus, femur, and tibia) of cynomolgus monkeys. Here, we apply the perfusion method to obtain BMCs from the ilium of cynomolgus monkeys, since BMCs are usually collected from the ilium by the conventional aspiration method in humans. The perfusion method consists of two approaches: transverse iliac perfusion and longitudinal iliac perfusion. BMCs harvested by the perfusion method from the long bones and ilium were compared with those collected from the ilium by the aspiration method. The contamination of BMCs with peripheral blood, determined by the frequencies of CD4+ and CD8+ T cells, was significantly lower in BMCs obtained from the ilium or long bones by the perfusion method (CD4+ plus CD8+ T cells <4%) than in those obtained by the iliac aspiration method (CD4+ plus CD8+ T cells >20%). However, the numbers of immature myeloid cells, such as myeloblasts, promyelocytes, myelocytes, and metamyelocytes, were higher in BMCs obtained by the iliac perfusion method than in those obtained by the iliac aspiration method. The assays for in vitro colony-forming unit in culture revealed that progenitor activity was significantly higher in BMCs obtained by the perfusion method than in those obtained by the aspiration method. These findings suggest that the contamination of BMCs with peripheral blood is much less when using the perfusion method than when using the aspiration method. To determine the best site for harvesting BMCs by the perfusion method, age-dependent changes in BMCs harvested by the perfusion method from the long bones and ilium were examined. The numbers of BMCs varied in the long bones (humerus > femur > tibia) and showed age-dependent decreases, whereas they remained similar in the ilium of cynomolgus monkeys from 3 years to 6 years of age. However, in cynomolgus monkeys, BMC harvesting by the perfusion method from the ilium (but not from the long bones) is found to involve the risk of fat emboli, particularly when the BMCs are quickly perfused under high pressure. These findings suggest, even in humans, that the perfusion method is better than the aspiration method, and that the best site for collection of BMCs is the humerus.