TGF-alpha sustains clonal expansion by promoter-dependent, chemically initiated rat hepatocytes

A series of promoting and non-promoting barbiturates and hydantoins were examined for their ability to sustain the growth of a phenobarbital (PB)-dependent hepatocyte line in cell culture. The effective liver tumor promoters, pentobarbital, allobarbital and 5- ethyl-5-phenylhydantoin, replaced PB and supported 6/27C1 hepatocyte colony formation in vitro at 52-87% of the level induced by PB. The weak promoters secobarbital and amobarbital supported colony formation at only 11-19% of the PB control. A significant correlation was observed for in vivo and in vitro promotion activities of barbiturates and hydantoins, indicating that clonal expansion by 6/27C1 hepatocytes was promoter-dependent. Cell density also appeared to influence hepatocyte growth in vitro. Hepatocyte colonies acquired the ability to grow in the absence of PB, such that after 10 days incubation with PB, approximately 50% of colonies continued to grow in the absence of promoter. This phenomenon of clone-size-dependent hepatocyte growth suggested the operation of an autocrine growth factor pathway. Addition of the hepatocyte mitogen and autocrine growth factor, transforming growth factor-alpha (TGF-alpha), to culture medium lacking PB induced a dose-dependent increase in 6/27C1 hepatocyte colony formation. At the optimal concentration of 3 ng/ml, TGF-alpha sustained hepatocyte clonal expansion at 84% of the level induced by 2 mM PB. Individual 6/27C1 colonies that grew from single cells in the presence of TGF-alpha were tested for promoter-dependent colony formation. Either PB or TGF-alpha supported colony formation by these cells at similar levels and when combined at optimal concentrations, the response appeared to be saturated. When these factors were tested in combination at suboptimal concentrations, the two compounds were additive for supporting colony formation by the parental 6/27C1 line. The ability of TGF-alpha to replace PB and sustain hepatocyte clonal expansion was confirmed with the tumorigenic 6/15 hepatocyte line. These results suggest that TGF- alpha and PB may promote hepatocarcinogenesis by stimulating a common signal transduction pathway.      

Upfront consolidation treatment with 131I-mIBG followed by myeloablative chemotherapy and hematopoietic stem cell transplantation in high-risk neuroblastoma

Importance::131I-metaiodobenzylguanidine ( 131I-mIBG) has a significant targeted antitumor effect for neuroblastoma. However, currently there is a paucity...     

染料木黄酮对乳鼠颅盖骨成骨细胞增殖分化的影响及其与白细胞介素6的关系

目的:观察染料木黄酮对成骨细胞活性的影响及其相关机制。方法:实验于2001-05/2003-05在卫生学环境医学研究所实验室完成。①成骨细胞培养:无菌条件下分离出生3d的乳鼠颅盖骨,剪碎,加入胰蛋白酶和Ⅱ型胶原酶,用含体积分数为0.1的胎牛血清的F-12培养基重悬,调整细胞浓度后接种于25mL细胞培养瓶,Ⅱ代细胞用于实验。②实验方法:实验分为染料木黄酮组、雌激素组和对照组(吐温20),染料木黄酮剂量分别为10-5,10-6、10-7mol/L,雌激素剂量分别为10-9,10-10mol/L,培养48,72h后,应用MTT和3H-TdR掺入实验观察不同剂量的染料木黄酮和雌激素对成骨细胞活性影响,免疫组化的方法测定白细胞介素6表达。结果:①A570nm值:培养48h,染料木黄酮10-5,10-6,10-7mol/L组分别比对照组增加105%,136%和143%;10-9,10-10mol/L雌激素组分别比对照组增加84%和100%;培养72h,染料木黄酮3个剂量组分别比对照组增加93%,113%和146%,各剂量组与对照组相比均有显著性差异(P<0.05)。②3H-TdR掺入量:10-5,10-6,10-7mol/L染料木黄酮组分别比对照组增加0.47,11.29,6.45倍;10-9和10-10mol/L雌激素组增加15.4倍和16.5倍(P<0.05)。③白细胞介素6表达:各组成骨细胞周围均有较强的呈棕色的阳性颗粒,但染料木黄酮组组与对照组相比无明显差别。结论:①10-5～10-7mol/L染料木黄酮和雌激素一样可促进成骨细胞增殖和DNA合成。②染料木黄酮不是通过促进白细胞介素6表达来促进成骨细胞增殖与分化。     

Impact of information and communication technology on child health

This article provides a general framework for understanding the use of information and communication technology in education and discusses the impact of computer usage on students' health and development. Potential beneficial and harmful effects of computer use by children are discussed. Early epidemiological and laboratory studies have indicated that children are at least of similar risk of developing musculoskeletal and vision problems as adults, and musculoskeletal and visual health problems developed in childhood are likely to persist into adulthood. This article, therefore, aims to provide a reflection on the deficits of existing policy and recommendations for child‐specific guidelines in computer use.     

Undetected chronic obstructive pulmonary disease and asthma in people over 50 years with persistent cough

Background

Chronic obstructive pulmonary disease (COPD) and asthma are underdiagnosed in primary care.

Aim

To determine how often COPD or asthma are present in middle-aged and older patients who consult their GP for persistent cough.

Design of study

A cross-sectional study in 353 patients older than 50 years, visiting their GP for persistent cough and not known to have COPD or asthma.

Setting

General practice in the Netherlands.

Method

All participants underwent extensive diagnostic work-up, including symptoms, signs, spirometry, and body plethysmography. All results were studied by an expert panel to diagnose or exclude COPD and/or asthma. The reproducibility of the panel diagnosis was assessed by calculation of Cohen''s κ statistic in a sample of 41 participants.

Results

Of the 353 participants, 102 (29%, 95% confidence interval [CI] = 24 to 34%) were diagnosed with COPD. In 14 of these 102 participants, both COPD and asthma were diagnosed (4%, 95% CI = 2 to 7%). Asthma (without COPD) was diagnosed in 23 (7%, 95% CI = 4 to 10%) participants. Mean duration of cough was 93 days (median 40 days). The reproducibility of the expert panel was good (Cohen''s κ = 0.90).

Conclusion

In patients aged over 50 years who consult their GP for persistent cough, undetected COPD or asthma is frequently present.     

A comparison of bone mineral density in oligomenorrhoeic adolescents with polycystic ovaries and normal ovaries

We evaluated whether the presence of polycystic ovaries in adolescent girls as a cause of oligomenorrhoea and amenorrhoea would pose any protective effect against osteoporosis or low bone mineral density (BMD) compared with girls having similar menstrual dysfunction but normal ovaries. A cross-sectional observational study was done in consecutive girls, aged between 16 and 19 years, presenting to the adolescent gynaecology clinic with oligomenorrhoea or amenorrhoea. All patients underwent full hormonal profile assessment, pelvic ultrasound for ovarian morphology, bio-impedance estimation of body fat, and dual-energy X-ray absorptiometry and quantitative peripheral computed tomography scans to determine BMD in axial and appendicular skeletal sites. Polycystic ovaries were diagnosed according to ultrasound morphology. These were then compared with an age-matched eumenorrhoeic control group that had undergone the same evaluation. Of 45 patients with oligomenorrhoea or amenorrhoea, 14 (31%) were diagnosed to have polycystic ovaries, while the other 31 had normal ovaries. The control group consisted of 45 age-matched eumenorrhoeic girls. The group with normal ovaries had lower BMD at the lumbar spine and hip, as well as lower total tibial volumetric BMD, than the eumenorrhoeic controls, but there were no significant differences between the group with polycystic ovaries and eumenorrhoeic controls. We conclude that adolescents with oligomenorrhoea and amenorrhoea with normal ovaries had lower BMD than eumenorrhoeic ones, but those with polycystic ovaries had BMD values comparable to those of eumenorrhoeic controls despite their menstrual dysfunction.