Bone Metastases from Soft Tissue Sarcomas

The incidence, distribution, time of appearance, and radiologic findings of bone metastases from soft tissue sarcomas, exclusive of lymphomas, were evaluated in 320 patients with soft tissue sarcomas. Thirty patients (9.4%) had evidence of 58 bone metastases. Five of 30 patients presented with metastases, and 25 of 30 patients developed metastases up to 66 months after presentation with a mean time interval of 21.3 months. The incidence of skeletal metastases differed among histologic subtypes of sarcomas; alveolar soft part sarcoma (5 of 8), dedifferentiated liposarcoma (2 of 4), angiosarcoma (2 of 4), and rhabdomyosarcoma (5 of 16) tended to show a higher incidence of bone metastases. The sarcomas metastasized to the regional bones close to the primary tumor in 16 (53%) of 30 patients and to the axial bones in 18 (60%). On conventional radiographs, the osseous metastases demonstrated predominantly osteolytic changes, and evidence of pathological fracture was observed in 31% of 58 metastases.     

Degradation of methyl and ethyl mercury into inorganic mercury by oxygen free radical-producing systems: Involvement of hydroxyl radical

Degradation of methyl mercury (MeHg) and ethyl Hg (EtHg) with oxygen free radicals was studied in vitro by using three well-known hydroxyl radical (OH)-producing systems, namely Cu²⁺-ascorbate, xanthine oxidase (XOD)-hypoxanthine (HPX)-Fe(III)EDTA and hydrogen peroxide (H₂O₂)-ultraviolet light B. For this purpose, the direct determination method for inorganic Hg was employed. MeHg and EtHg were readily degraded by these three systems, though the amounts of inorganic Hg generated from MeHg were one half to one third those from EtHg. Degradation activity of XOD-HPX-Fe(III)EDTA system was inhibited by Superoxide dismutase, catalase and the OH scavengers and stimulated by H₂O₂. Deletion of the OH formation promoter Fe(III)EDTA from XOD-HPX-Fe(III)EDTA system resulted in the decreased degradation of MeHg and EtHg, which was enhanced by further addition of the iron chelator diethylenetriamine pentaacetic acid. In all these cases, a good correlation was observed between alkyl Hg degradation and deoxyribose oxidation determining OH. By contrast, their degradation appeared to be unrelated to either Superoxide anion production or H₂O₂ production alone. We further confirmed that H₂O₂ (below 2 mM) itself did not cause significant degradation of MeHg and EtHg. These results suggested that OH, but not and H₂O₂, might be the oxygen free radical mainly responsible for the degradation of MeHg and EtHg.     

谷胱甘肽对顺铂致猴和大鼠肾细胞毒性的影响

目的 探讨顺铂对猴和大鼠肾小管上皮细胞的毒性及半胱氨酸和GSH合成抑制剂BSO对其影响。方法 从猴和大鼠的肾脏分离培养的肾小管上皮细胞接种于96孔培养板，培养24h后加入一系列浓度的顺铂，或在加入顺铂前16和4h，分别加入GSH合成抑制剂BSO和GSH的前体物半胱氨酸，继续培养，分别在8、24和48h3个时间点用MTT方法检测细胞存活率。结果 顺铂对猴和大鼠肾小管上皮细胞有明显的毒性，在不同的时间点有各自的剂量—反应关系，顺铂对大鼠肾小管上皮细胞在8、24和48h 3个时间点半数抑制浓度(IC50)分别为1105．12、513．25和71．24μmol/L；BSO能使3组IC50均降低，分别为66．00、21．43和7．23μmol/L，而半胱氨酸则使3组IC50均升高，均大于5000μmol/L；顺铂对猴肾小管上皮细胞在3个时间点IC50分别为3026．00、1238．35和664．44μmol/L；BS0使3组ICD分别降为480．10、108．61和31．43μmol/L，而半胱氨酸则可使3组IC50均大于5000μmol/L。结论 顺铂对猴和大鼠肾小管上皮细胞均具有明显毒性作用，对猴的毒性低于大鼠；BS0可增强顺铂的细胞毒性，对大鼠的影响大于猴，而半胱氨酸对两种细胞的保护作用无显著性差异，提示细胞内GSH对顺铂所致肾小管上皮细胞毒性有保护作用。     

Ooplasmic round spermatid nuclear injection procedures as an experimental treatment for nonobstructive azoospermia

Purpose: Our objective was to apply ooplasmic round spermatid nuclear injections for the treatment of nonobstructive azoospermia. Materials: Participants were nine azoospermic men who had previously undergone diagnostic testicular biopsy. Spermatogenetic arrest was diagnosed at the round spermatid stage (n=6) or primary spermatocyte stage (n=3). A second (therapeutic) testicular biopsy was performed and round spermatid nuclei were recovered from all the participants. Results: Forty-nine mature oocytes were successfully injected with nuclei and then cultured for 72 hr. Twenty-four embryos were transferred to nine women. No pregnancy was achieved. Conclusions: Round spermatids can be recovered from therapeutic testicular biopsy material of men negative for round spermatids in previous routine diagnostic testicular biopsy specimens. Round spermatid nuclear injections may play a role in the treatment of nonobstructive azoospermia.     

Cytotoxic Mechanisms of FK317, a New Class of Bioreductive Agent with Potent Antitumor Activity

FK317 is a member of a new class of bioreductive agents that exhibit strong cytotoxicity against various human cancer cells. The effect of FK317 was found to be stronger than that of mitomycin C (MMC), adriamycin (ADR) or cisplatin (CDDP). Alkaline elution analysis indicated that FK317 formed interstrand DNA-DNA and DNA-protein cross-links in cells. On the other hand, no DNA single-strand breaks were observed in the cells treated with FK317. In a cell-free system the deacetylated metabolites produced cross-linked DNA under reductive conditions, though FK317 itself did not form DNA-DNA cross-links. In order to elucidate the metabolic activation mechanisms, we established an FK317-resistant subline from human non-small cell lung cancer cells (Lu99) by stepwise and brief exposure (1 h) to FK317. The resistant subline (Lu99/317) showed cross-resistance to MMC and carboquone (CQ), but not to ADR or CDDP. DT-diaphorase, which is one of the activation enzymes of MMC and CQ, was deficient in Lu99/317 cells as determined by enzyme activity assay. However, the levels of NADPH:cytochrome P450 reductase, which is another activation enzyme for MMC and CQ, were comparable in resistant and parent cell lines. Treatment of the cells with dicumarol, an inhibitor of DT-diaphorase, reduced the cytotoxicity of FK317 to Lu99 cells, but not to Lu99/317 cells. These results indicate that deacetylation of FK317 is necessary for its reductive activation, and deacetylated FK317 is reduced by DT-diaphorase to form an active metabolite, which produces DNA-DNA interstrand and DNA-protein cross-links that lead to cell death.     

正常双胎及单胎胎儿大脑中动脉搏动指数变化的比较

目的 探讨正常双胎妊娠期间胎儿大脑中动脉搏动指数的变化;并与正常单胎进行比较.方法 采用彩色多普勒超声对34例正常双胎及176例正常单胎胎儿从孕23周至孕35周进行大脑中动脉搏动指数测定.结果 正常双胎胎儿大脑中动脉搏动指数随孕周呈逐渐下降趋势,与正常单胎胎儿比较,孕29周前该值为低,以后较之略高.结论 孕29周后双胎胎儿大脑中动脉血流阻力比单胎其值为高.     

Hyperpnoeic response independent of limb movements at exercise onset in mice

We have shown that constant-load treadmill exercise in mice produces an abrupt ventilatory increase to a maximal level at exercise onset. We examined what caused this abrupt response. We measured ventilation during 30-min constant-load exercise on a treadmill, below the lactate threshold, in conscious mice. Video analysis showed that hyperpnoea started before locomotion began. Incremental changes in speed did not further increase ventilation during the early phase of exercise. Next, we measured ventilatory responses to a sudden movement of the treadmill belt on which the mice were kept in a stationary position by a mesh cover. Hyperpnoea started concurrently with the sudden belt movement. In the absence of locomotion, ventilation increased to the extent reached during exercise hyperpnoea. Finally, the abrupt response showed plasticity but was attenuated by experience. The present study shows the importance of factors independent of limb movements in the hyperpnoeic response during the early phase of treadmill exercise in mice.     

Occupational Factors and Problem Drinking among a Japanese Working Population

Problem drinking is a serious public health problem in the workplace. However, few Japanese epidemiological studies have investigated the occupational characteristics of problem drinking. The purpose of this study is to clarify the occupational risk factors for problem drinking among a Japanese working population. We used data from a random-sampling survey about mental health and suicide, conducted among Hamamatsu City residents aged 15 to 79 yr old during May and June in 2008. The relation between occupational factors and problem drinking was analyzed with multiple logistic regression models stratified by gender. CAGE questionnaire was used to assess problem drinking. With regard to employment types, problem drinkers were more prevalent among self-employed women. With regard to occupational types, clerical and service professions had more problem drinkers of either sex, while administrative/managerial and sales professions had more women with such problem. With regard to company size, male problem drinkers were more prevalent in smaller companies than in larger ones. These results indicate that the prevalence of problem drinkers in the workplace depends on where one works. It is necessary to consider these characteristics to provide effective measures to address problem drinking in the workplace.     

Chemosensitizing Effect of Saikosaponin B on B16F10 Melanoma Cells

Cancer cell resistance to chemotherapy is one of the obstacles for better cancer treatment, and inflammatory signaling pathways, such as NF-κB signaling pathway, have been recognized to be involved in such chemoresistance. In this study, we aim to identify a new approach for overcoming cancer chemoresistance by using natural compounds. As a result of screening by using Murine B16F10 melanoma cell line constitutively expressing NF-κB luciferase reporter gene, we identified Saikosaponin B2 as an effective inhibitor for etoposide-induced NF-κB activation in B16F10NFkB cells. Saikosaponin B2 sensitized etoposide-induced cell death in B16F10 melanoma cells through the induction of apoptosis. Along with apoptosis induction, we observed an induction of γ-H2AX expression, which is a molecular signature for DNA damage, upon the combination treatment of etoposide and Saikosaponin B2. Among Saikosaponin family compounds, we found that Saikosaponin B1, but not Saikosaponin A, sensitized etoposide-induced cytotoxicity implicating the structural requirement of Saikosaponin B for such chemosensitization. By testing the combination of Saikosaponin B1 and B2 with 9 clinical anticancer drugs, Saikosaponin B showed a certain preference in the combination with those tested anticancer drugs. Collectively, we conclude Saikosaponin B can be an attractive adjuvant for enhancing the clinical effect of cancer chemotherapy.