Mutation and downregulation of the transforming growth factor beta type II receptor gene in primary squamous cell carcinomas of the head and neck

In the present study, we analyzed 28 squamous cell carcinomas of the head and neck (SCCHN) for mutations in the coding region of TbetaR-II using 'Cold' SSCP and automatic DNA sequencing analyses. Twenty-one percent (6/28) of the SCCHN examined contained TbetaR-II mutations compared with patient-matched normal tissues. These alterations included five missense mutations (A:T-->G:C transitions in codons 250, 401, 448 and 488, and a G:C-->T:A transversion in codon 373), and a 38- bp deletion between nucleotides 1825 to 1862. In addition to these code- altering mutations, one case exhibited a silent mutation (A:T-->G:C transition in codon 451) and three cases contained one of two potential population polymorphisms (codons 354 and 389). In contrast to colon and gastric cancers exhibiting microsatellite instability (MI) or replication errors (RER+), no 'indirect' frameshift mutations were identified within a 10-bp polyadenine repeat present in the TbetaR-II coding sequence. All of the mutations in the present study occurred within the highly conserved serine/threonine kinase domain and represent the first report of such 'direct' TbetaR-II mutations in primary human tumors. In addition, we analyzed a subset of SCCHN and corresponding normal samples for TbetaR-II mRNA expression using semi- quantitative multiplex RT-PCR. Expression of TbetaR-II was decreased by 24% to 74% in 20 of 23 SCCHN (87%) compared with patient-matched normal tissues. Taken together, the results from this study suggest that alterations in the nucleic acid sequence and mRNA expression of TbetaR- II are prevalent events in the development of SCCHN, which may deregulate cell cycle control.      

Effects of 1,8-cineole on electrophysiological parameters of neurons of the rat superior cervical ganglion

• 1 1,8‐Cineole is a non‐toxic small terpenoid oxide believed to have medicinal properties in folk medicine. It has been shown to have various pharmacological effects, including blockade of the compound action potential (AP). In the present study, using intracellular recording techniques, we investigated the effects of 1,8‐cineole on the electrophysiological parameters of neurons of the superior cervical ganglion (SCG) in rats.
• 2 1,8‐Cineole (0.1–6 mmol/L) showed reversible and concentration‐dependent effects on various electrophysiological parameters. At 3 and 6 mmol/L, but not at 0.1 and 1 mmol/L, 1,8‐cineole significantly diminished the input resistance (R_i) and altered the resting potential (E_m) to more positive values. At 6 mmol/L, 1,8‐cineole completely blocked all APs within 2.7 ± 0.6 min (n = 12). In neurons exposed to 3 and 1 mmol/L 1,8‐cineole, the effects regarding excitability varied from complete AP blockade to minor inhibition of AP parameters. The depolarization of E_m and the decrease in R_i induced by 6 mmol/L 1,8‐cineole were unaltered by 200 µmol/L niflumic acid, a well known blocker of Ca²⁺‐activated Cl^? currents.
• 3 Significant correlations (Pearson correlation test) were found between changes in E_m and decreases in AP amplitude (r = –0.893; P < 0.00282) and maximum ascendant inclination (r = –0.799; P < 0.0173), but not for maximum descendant inclination (r = 0.598; P < 0.117). Application of current to restore the transmembrane potential equal to control E_m values in the presence of 6 mmol/L 1,8‐cineole resulted in the partial recovery of AP.
• 4 The present study shows that 1,8‐cineole effectively blocks the excitability of SCG neurons, probably through various mechanisms, one of which acts indirectly via depolarization of the neuronal cytoplasmatic membrane.

     

Methotrexate for the treatment of refractory Crohn's disease.

BACKGROUND: Previous studies suggested that methotrexate has beneficial effects in patients with Crohn's disease. We report our experience with this agent in patients with chronic active Crohn's disease who previously failed to improve with conventional treatment, including azathioprine in most cases. METHODS: Between June 1988 and June 1992, 39 patients with refractory Crohn's disease were treated with methotrexate. In patients with active disease, clinical remission was defined by a Harvey-Bradshaw index of less than 4. For patients also taking corticosteroids, the dates of remission and complete steroid withdrawal were recorded. For patients who achieved clinical remission, and those in clinical remission when methotrexate was started, the relapse rate on methotrexate therapy was noted. RESULTS: In the 37 patients with active disease at methotrexate initiation, the probability of remission was 72% at 3 months. The probability of remission and steroid withdrawal was 42% at 12 months. In patients on clinical remission, the probability of relapse on methotrexate was 58% at 12 months. Twenty-two patients experienced side-effects, but these only warranted methotrexate discontinuation in four cases. CONCLUSIONS: Methotrexate appears effective in most patients with refractory Crohn's disease and its short-term toxicity is acceptable, but the long-term benefit seems more limited.     

分光光度法测定金蝉花中多糖的含量

目的建立金蝉花药材中多糖的含量测定方法.方法采用分光光度法测定多糖含量.结果金蝉花中多糖含量为24.16 mgg-1,平均回收率为97.37%,RSD＝2.34%,n＝5.结论本法简便、准确、灵敏、重现性好,为金蝉花药材的质量控制提供了依据.     

磺酸基邻苯二甲酰亚氨甲基酞菁锌C光动力效应诱导肿瘤细胞凋亡

目的：研究新型光敏剂磺酸基邻苯二甲酰亚胺甲基酞菁锌Ｃ光动力效应诱导肿瘤细胞凋亡,探索其光动力杀伤机理,方法：用ＡＯ／ＥＢ荧光染色法,流式细胞仪及电子显微镜观察该光敏剂光动力效应与人白血病Ｋ５６２细胞形态,超微结构及ＤＮＡ含量的影响,结果：药物作用２ｈ,以红外照射后继续培养３ｈ以上,就可出现明显的细胞凋亡特性征改变。结论：新型光敏剂磺酸基邻苯二甲酰亚氨甲基酞菁锌Ｃ光动力杀伤作用与诱导肿瘤细胞凋亡有关