Takehiro Serikawa

Gene delivery using liposome technology.

Development of more reliable liposomal formulations and preparation methods which can be used for gene therapy instead of commonly used viral vectors is expected. We have already developed the freeze-dried empty (non-drug-containing) liposomes (FDEL) method for mass-production of liposomal products. After these freeze-dried empty liposomes are rehydrated with aqueous drug solutions, many kinds of drugs can be encapsulated highly efficiently, and particle size can be controlled well. This study evaluated the usefulness of this FDEL method for preparation of liposomes containing DNA with a particular attention to the stability of DNA. When the liposomes were prepared by the conventional lipid-film method on a relatively large scale with use of a Potter-homogenizer (a teflon homogenizer), significant degradation and conformational change of DNA was observed during homogenization. Loss of DNA was also significant after extrusion for sizing and sterilization; residual DNA in the final preparation was hardly detected. When the FDEL method was used, on the other hand, no degradation, conformational change or loss of DNA was observed, and particle size was easily controlled. Moreover, there was no significant difference in luciferase activity between the lipid-film method used on a small scale with use of a vortex mixer and the FDEL method after transfection of tumor cells (HRA, HEC-1A and Colo320DM) by the liposomes containing DNA (PGV-C). These findings suggest that the FDEL method is very useful for preparation of liposomes containing DNA.

Management of patients with pregnancy-associated gastric cancer in Japan : a mini-review

Gastric cancer associated with pregnancy is quite rare, and is most often diagnosed at an advanced stage. Furthermore, physicians are confronted with two conflicting issues in this condition: the need for early treatment of the maternal gastric cancer and the continuation of the pregnancy. To clarify the characteristics of pregnancy-associated gastric cancer and to obtain useful information that would help us choose the best treatment strategy for pregnancy-associated gastric cancer, we reviewed the existing literature, using the key words “pregnancy” and “gastric cancer”. We were able to accumulate 136 cases, including 100 cases reported previously in Japan, and 1 case that we report here. We analyzed a total of 137 cases in the present study. With respect to the stage of gastric cancer, 92.5% of the patients studied had advanced gastric cancer, and only 45.3% of the patients underwent gastrectomy, including incomplete resection. Accordingly, the prognosis was very poor; the 1- and 2-year survival rates were 18.0% and 15.1%, respectively. However, the number of patients found to have early gastric cancer by endoscopic examination has been increasing recently. An endoscopic examination should be conducted immediately in pregnant patients presenting with persistent gastrointestinal symptoms for the differential diagnosis of hyperemesis gravidarum. When an endoscopic examination reveals that pregnant patients have gastric cancer, a therapeutic plan should be promptly formulated, in accordance with the number of weeks of gestation, by a medical team consisting of specialists in perinatal obstetrics and gastric cancer specialists.

Changes in Fetal Circulation Associated with Congenital Heart Disease and Their Effects on Fetal Growth

Objective: Our aim was to investigate the association between fetal growth and cerebrovascular resistance in fetuses with congenital heart disease (CHD). Methods: Fetal echocardiography was performed to measure the biparietal diameter, abdominal circumference, femur length, estimated fetal body weight, middle cerebral artery (MCA) resistance index (RI) and umbilical artery (UA) RI in 44 fetuses with CHD and 140 normal fetuses at a gestational age of 28–34 weeks. Results: Fetuses with CHD exhibited significantly lower values for femur length, estimated fetal body weight at the third trimester, body weight, length, and chest circumference at birth than normal controls. The percentages of fetuses showing MCA RI values <10th percentile and UA RI values >90th percentile were significantly higher in the CHD group than in the control group. However, there were no significant differences in any biometric parameters measured between cases with MCA RI values ≧10th percentile and values <10th percentile. Conclusions: Growth restriction and blood flow changes were observed significantly more frequently in fetuses with CHD than in those without CHD. Further studies are necessary to clarify the association between fetal growth and dynamic changes in fetal circulation.

Clinical significances of magnetic resonance imaging in prenatal diagnosis of vasa previa in a woman with bilobed placentas

We report a case of a pregnant woman diagnosed as having vasa previa by magnetic resonance imaging (MRI). A parous woman was referred to our hospital at 31 weeks of gestation due to suspicion of placenta previa. Transvaginal ultrasound examination together with the Doppler techniques showed a fetal vessel on a lesion of low and high mixed echogenecities over the internal os, but could not confirm whether it was placental tissue or not. MRI demonstrated that it was not placenta but a hemorrhage between bilobed placentas and that the vessel was running over the internal os freely from the placenta. At 34 weeks of gestation, emergency cesarean section was performed due to increasing vaginal bleeding. MRI should be useful in the diagnosis of vasa previa when the relation between the position of the placenta and that of suspicious vessels cannot be adequately evaluated by ultrasound.

Preoperative ultrasound-guided needle biopsy of 63 uterine tumors having high signal intensity upon T2-weighted magnetic resonance imaging.

Objective The differential diagnosis between uterine sarcoma and benign leiomyoma is difficult when made only by magnetic resonance imaging (MRI); it usually requires an additional preoperative diagnostic procedure. We report our results using ultrasound-guided needle biopsy for these types of uterine tumors. Methods Ultrasound-guided needle biopsy was performed on 63 patients with uterine smooth muscle tumors suspected of malignancy by MRI. We compared the results of presurgical biopsy against the postsurgical pathology of the tumor. Results Among 63 patients with a high signal intensity of the uterine tumor on T2-weighted MRI (1 case was undetermined), 12 cases (19.3%) were diagnosed by the needle biopsy as malignant, and 51 cases (80.6%) were benign. Among the 12 diagnosed as malignant tumors, 11 had surgery performed, and one was treated with chemotherapy. Among the 51 patients diagnosed with a benign tumor, 27 had surgery performed, and 24 were put on a wait-and-see clinical follow-up schedule. One of the 27 surgical patients with a benign tumor had a postsurgical diagnosis of a low-grade endometrial stromal sarcoma. In the 38 cases where surgery was performed, we found the sensitivity, specificity, and the positive and negative predictive values of the needle biopsy were 91.7%, 100%, 100%, and 96.2%, respectively. Conclusions Ultrasound-guided needle biopsy may be a reliable preoperative diagnostic procedure for uterine tumors with suspected malignancy.

Successful twin pregnancy in a patient with parkin-associated autosomal recessive juvenile parkinsonism

BackgroundPregnancy in patients with Parkinson disease is a rare occurrence. To the best of our knowledge, the effect of pregnancy as well as treatment in genetically confirmed autosomal recessive juvenile parkinsonism (ARJP) has never been reported. Here, we report the first case of pregnancy in a patient with ARJP associated with a parkin gene mutation, ARJP/PARK2.Case presentationA 27-year-old woman with ARJP/PARK2 was diagnosed as having a spontaneous dichorionic/diamniotic twin pregnancy. Exacerbation of motor disability was noted between ovulation and menstruation before pregnancy as well as during late pregnancy, suggesting that her parkinsonism might have been influenced by fluctuations in the levels of endogenous sex hormones. During the organogenesis period, she was only treated with levodopa/carbidopa, although she continued to receive inpatient hospital care for assistance in the activities of daily living. After the organogenesis period, she was administered sufficient amounts of antiparkinsonian drugs. She delivered healthy male twins, and psychomotor development of both the babies was normal at the age of 2 years.ConclusionPregnancy may worsen the symptoms of ARJP/PARK2, although appropriate treatments with antiparkinsonian drugs and adequate assistance in the activities of daily living might enable successful pregnancy and birth of healthy children.

Adenocarcinoma arising from respiratory ciliated epithelium in benign cystic teratoma of the ovary: A case report with analyzes of the CT, MRI, and pathological findings

The malignant transformation of mature cystic teratoma is rare, thus occurring in only 1–2% of all cases. The most common malignancy arising in mature cystic teratoma is squamous cell carcinoma. Adenocarcinoma occurs with less frequency. We herein present a patient with an ovarian mature cystic teratoma who demonstrated a malignant transformation to well‐differentiated adenocarcinoma. Malignant transformation was diagnosed preoperatively by contrast enhanced computed tomography (CT) and magnetic resonance imaging (MRI). Microscopically and immunohistochemically, the adenocarcinoma was considered to have arisen from the ciliated respiratory epithelium. After a 28‐month of follow‐up period, she remains free of the disease. This is the third reported case of adenocarcinoma arising in the respiratory epithelium of an ovarian mature cystic teratoma. Contrast enhanced CT and MRI are useful for making a preoperative diagnosis and an immunohistochemical study is helpful for defining its origin.

Enhancement of Gene Expression Efficiency Using Cationic Liposomes on Ovarian Cancer Cells

We performed transfection using cationic liposome. According to the gene expression level, lined cells were divided into two groups, high and low. Introduced gene was monitored with a confocal laser-scanning microscope. The percentages of the cells introduced gene reached more than 90% in all line. Then, introduced gene was stable in high group, while in low group, it significantly decreased. With lysosomotrophic agents, gene expression efficiency was significantly reduced. With colchicine, gene expression efficiency did not change in high group, but was significantly elevated in low group. A method of liposomal transfection could be effective, particularly in low group.

Pregnancy with congenital unilateral absence of a pulmonary artery

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A case report of fatal tumor lysis syndrome after chemotherapy in a pregnant patient with Burkitt's lymphoma

A 35‐year‐old Japanese woman in the 24th week of gestation with bilateral breast enlargement was referred to hospital. She was diagnosed with Burkitts lymphoma and admitted for detailed evaluation and treatment. Early delivery and subsequent chemotherapy was chosen after considering the gestational week, her general condition and the wishes of the patient and her husband. She gave birth to a male infant by cesarean section in the 25th week of gestation. It had been planned to begin high‐dose chemotherapy, such as CODOX‐M/IVAC, on day 7 of the puerperium; however, her general condition worsened and chemotherapy was therefore begun on day 2 after the birth. Eight hours after chemotherapy (cyclophosphamide, vincristine and doxorubicin), she developed cardiac arrest due to tumor lysis syndrome. Despite medical treatment, her bleeding tendency did not improve and she died of respiratory failure with alveolar bleeding five days after chemotherapy.