The pleiotrophin-ALK axis is required for tumorigenicity of glioblastoma stem cells.

Increasing evidence suggests that brain tumors arise from the transformation of neural stem/precursor/progenitor cells. Much current research on human brain tumors is focused on the stem-like properties of glioblastoma. Here we show that anaplastic lymphoma kinase (ALK) and its ligand pleiotrophin are required for the self-renewal and tumorigenicity of glioblastoma stem cells (GSCs). Furthermore, we demonstrate that pleiotrophin is transactivated directly by SOX2, a transcription factor essential for the maintenance of both neural stem cells and GSCs. We speculate that the pleiotrophin-ALK axis may be a promising target for the therapy of glioblastoma.

Identification of Sc-type ILV6 as a target to reduce diacetyl formation in lager brewers' yeast.

Diacetyl causes an unwanted buttery off-flavor in lager beer. It is spontaneously generated from α-acetolactate, an intermediate of yeast's valine biosynthesis released during the main beer fermentation. Green lager beer has to undergo a maturation process lasting two to three weeks in order to reduce the diacetyl level below its taste-threshold. Therefore, a reduction of yeast's α-acetolactate/diacetyl formation without negatively affecting other brewing relevant traits has been a long-term demand of brewing industry. Previous attempts to reduce diacetyl production by either traditional approaches or rational genetic engineering had different shortcomings. Here, three lager yeast strains with marked differences in diacetyl production were studied with regard to gene copy numbers as well as mRNA abundances under conditions relevant to industrial brewing. Evaluation of data for the genes directly involved in the valine biosynthetic pathway revealed a low expression level of Sc-ILV6 as a potential molecular determinant for low diacetyl formation. This hypothesis was verified by disrupting the two copies of Sc-ILV6 in a commercially used lager brewers' yeast strain, which resulted in 65% reduction of diacetyl concentration in green beer. The Sc-ILV6 deletions did not have any perceptible impact on beer taste. To our knowledge, this has been the first study exploiting natural diversity of lager brewers' yeast strains for strain optimization.

[Labial adhesion in a reproductive woman with difficulties of sexual intercourse and urination: a case report].

A 27-year-old female patient consulted us with chief complaints of difficulties of sexual intercourse and urination. On examination, the labia was found to be extensively fused at the midline, with a pinhole opening. We diagnosed it as labial adhesion. We operated on it under lumbar anesthesia. Four months after the operation, there were no symptoms of recurrence. Labial adhesion is thought to be caused by inflammation, lack of sexual activity and estrogen deficiency. It is not uncommon in children and post-menopausal women, but is extremely rare in reproductive women.

Prospective randomized study of antibiotic prophylaxis for nonlaparotomy surgery in benign conditions.

BACKGROUND: Although postoperative infections continue to be a major problem in gynecologic surgery, there is still no consensus on the efficacy of antibiotic prophylaxis. METHODS: This prospective randomized trial was conducted to investigate the prevention of major operating site infections after nonlaparotomy surgery, with treatment regimens as follows: the first group of patients received 2 g of intravenous cefotiam dihydrochloride (CTM) on the induction of anesthesia, while the second group received 100 mg of oral cefpodoxime proxetil (CPDX- PR) twice daily, from day 0 to day 2. RESULTS: Nineteen of the 207 patients enrolled developed postoperative infections diagnosed by our simple criteria for postoperative infection. The frequency of febrile morbidity was not significantly less in patients who received CTM (9 cases; 8.6%) as compared with those in the CPDX-PR group (10 cases; 9.8%) (p = 0.56). CONCLUSION: The administration of oral CPDX-PR (100 mg, twice daily, for 3 days) appears to be a safe, cost-saving, convenient prophylaxis which reduces overall expense.

Twin-to-twin transfusion syndrome with hydrops: a retrospective analysis of ten cases.

We retrospectively studied 10 cases of twin-to-twin transfusion syndrome (TTTS) with fetal hydrops. TTTS was diagnosed sonographically between the 17-31 weeks of gestation. All twins were delivered by emergency cesarean section because of cardiac decompensation of one or both fetuses. The mean (+/-SD) age at diagnosis was 26.1 +/- 4.5 and the mean age at delivery was 28.8 +/- 2.0 weeks. Gestational age at birth was similar in survivors and nonsurvivors. However, surviving infants were diagnosed later in gestation (23.6 +/- 4.8 vs. 28.7 +/- 1.9 weeks; p < 0.01); and gestational age at appearance of hydrops were later in survivors (26.1 +/- 3.2 vs. 29.2 +/- 2.4 weeks; p < 0.05). Overall survival rate was 50% (10 of 20 infants). All survivors were delivered within 3 days after the appearance of fetal hydropic changes. Extrauterine treatment in earlier stages of TTTS might improve the outcome. Nevertheless, more aggressive intrauterine treatment should be considered in the most severe cases of TTTS developing before 24-25 weeks' gestation.

[A rare case of 2 free thrombi in left atrium with mitral stenosis].

A 64-year-old female was admitted with general fatigue and orthopnea. Preoperative echocardiography showed a free ball thrombus in the left atrium, mitral stenosis and severe tricuspid regurgitation. To avoid a herniation of thrombus to the mitral orifice, an emergency operation was performed. Two free and small mural thrombi were found in the left atrium. Thrombectomy, mitral valve replacement and tricuspid annuloplasty were performed successfully. Postoperative course was uneventful, and she was discharged in good condition on the 21st postoperative day.

Alveolar-arterial gas tension differences during progressive exercise in patients after the Fontan operation.

We investigated alveolar-arterial gas tension differences as a measurement of ventilatory impairment during exercise in patients who had undergone the Fontan operation. The ventilatory response to exercise in 13 operated patients was compared with that of 11 control subjects. The difference between end-tidal and arterial oxygen tension (P(ET-a)DO2) and between arterial and end-tidal carbon dioxide tension (P(a-ET)DCO2) as well as the physiologic dead space-tidal volume ratio were calculated during progressive treadmill exercise testing. In the Fontan group, P(ET-a)DO2 and P(a-ET)DCO2 were significantly higher than in control subjects and increased in parallel during the study period. The physiologic dead space-tidal volume ratio was higher in the Fontan group than in the control group, and the difference in these ratios between the values obtained using end-tidal carbon dioxide tension and those using arterial carbon dioxide tension correlated well with P(a-ET)DCO2 (r = -0.79 to -0.98, p < 0.001). The physiologic dead space-tidal volume ratio during exercise was significantly higher in patients with low exercise capacities than in those with high exercise capacities (p < 0.05). The alveolar-arterial gas tension differences during exercise were greater in Fontan patients than in control subjects. We conclude that the size of the physiologic dead space can be evaluated from measurements of arterial carbon dioxide tension and is correlated with impaired exercise capacity after the Fontan operation.

Prediction of engraftment after peripheral blood stem cell transplantation by CD34-positive cells in grafts.

A total of 91 peripheral blood stem cell collections were performed in 26 children with various malignant tumors and peripheral blood stem cell transplantations (PBSCT) were performed in 15 of the children. There was a positive correlation between logarithm of total CD34+ cells/kg and logarithm of colony-forming unit-granulocyte macrophage (CFU-GM)/kg (r = 0.86). The time elapsed until the white blood cells (WBC) exceeded 1000/microL was related to both CFU-GM (r = 0.67) and CD34+ cell count (r = 0.60). The number of days elapsed until platelet count exceeded 5 x 10(4)/microL was not related to the logarithm of CFU-GM count/10(5) per kg transfused (r = 0.47), but was related to the logarithm of CD34+ cell counts/10(6) per kg transfused (r = 0.73). The number of days elapsed until the reticulocytes exceeded 10% was not related to the logarithm of CFU-GM count/10(5) per kg (r = 0.52), but was related to the logarithm of CD34+ cell counts/10(6) per kg transfused (r = 0.91). Although CD34+ cell counts correlated with the number of CFU-GM, bone marrow regeneration rates in three lineages were predicted more accurately by the number of CD34+ cells transfused than by the number of CFU-GM. These results suggest that measurement of the CD34+ cell count may be useful in predicting bone marrow regeneration rate after PBSCT.

[An autopsy case of endocardial cushion defect (ECD) in an 82-year-old female].

In an 82-year-old female case of endocardial cushion defect (ECD), a systolic regurgitant murmur was heard at the apex, and her ECG showed atrial fibrillation without right bundle branch block or left axis deviation. An echocardiogram demonstrated atrial septal defect (ASD) and a cleft of the anterior mitral leaflet with calcification. She died of refractory congestive heart failure. Autopsy revealed ECD (intermediate type) with mitral and tricuspid cleft, and ASD (ostium primum type, 2.0 x 1.0 cm in diameter). In addition, mitral ring calcification and calcification of the cleft mitral valve was disclosed, causing mitral stenosis in addition to mitral regurgitation due to the cleft mitral valve. This was the second oldest Japanese autopsy case of ECD. We concluded that echocardiographic examinations, including color flow imaging, in aged patients with heart murmur are necessary to confirm the diagnosis of congenital heart disease in the aged.

[A case report of an advanced ovarian cancer (stage T4) treated with a total amount of 1815 mg of CDDP].

A case is reported of a 34-year-old female who complained of an adult head-sized tumor in the pelvis and was treated with a high dose of CDDP. On the first look operation, it was found impossible to perform reduction surgery because of severe adhesion and peritonitis carcinomatosa. To introduce a high concentration of an anti-cancer agent into the tumor tissue, we administered CDDP intravenously, intraperitoneally and intra-arterially to the total amount of 1815 mg. After this high dose combination chemotherapy, a second look operation was performed and the tumor was seen to be reduced. The patient is now in remission and is being followed up as an out-patient. The clinical course of this case had decided for us which route would be the most effective and would have the least side effect, also, how much of a dosage can be administered as a maximum adoptive dose of an anti-cancer agent, and what kind of a second-line chemotherapy is effective against resistant cancer cells.