Effects of PNU-109,291, a selective 5-HT1D receptor agonist, on electrically induced dural plasma extravasation and capsaicin-evoked c-fos immunoreactivity within trigeminal nucleus caudalis.

We studied the effects of PNU-109291 [(S)-(-)-1-[2-[4-(4-methoxyphenyl)-1-piperazinyl]ethyl]-N-methyl-isoc hroman-6-carboxamide], a receptor agonist showing 5000-fold selectivity for primate 5-HT1D versus 5-HT1B receptors (Ennis et al., J. Med. Chem. 41, 2180-2183), on dural neurogenic inflammation and on c-fos like immunoreactivity within trigeminal nucleus caudalis evoked by electrical and chemical activation of trigeminal afferents, respectively. Subcutaneous injection of PNU-109291 in male guinea pigs dose-dependently reduced dural extravasation of [125I]-labeled bovine serum albumin evoked by trigeminal ganglion stimulation with an IC50 of 4.2 nmol kg(-1). A dose of 73.3 nmol kg(-1) blocked the response completely. The selective 5-HT1B/1D receptor antagonist GR-127935 (> or = 2 micromol kg(-1) i.v.) prevented this effect. In addition, the number of c-fos immunoreactive cells within guinea pig trigeminal nucleus caudalis induced by chemical meningeal stimulation (intracisternally administered capsaicin) was reduced by more than 50% with PNU-109291 (> or = 122.2 nmol kg(-1) administered s.c. 45 min before and 15 min after capsaicin). These data indicate that the 5-HT1D receptor subtype plays a significant role in suppressing meningeal neurogenic inflammation and attenuating trigeminal nociception in these guinea pig models. Since 5-HT1D receptor mRNA and protein are expressed in trigeminal ganglia but not vascular smooth muscle, the 5-HT1D receptor subtype may become a useful therapeutic target for migraine and related headaches.     

Genetic mapping of "Lubag" (X-linked dystonia-parkinsonism) in a Filipino kindred to the pericentromeric region of the X chromosome.

"Lubag" is an X-linked disorder causing dystonia and parkinsonism that has only been described in families from the Philippines, principally from the island of Panay. We have established linkage between the disease phenotype "lubag" and DNA markers which span the Xp11.22-Xq21.3 region by using a large Filipino family with 8 affected men in three generations. These DNA markers define an interval of about 20 centimorgans in the pericentromeric region of the X chromosome as the most likely site of the disease locus XDPD (X-linked dystonia-parkinsonism). XDPD has a maximum multipoint log likelihood ratio score (Zmax) of about 4.6 over the interval from Xq12 to Xq21.31 (DXS159-DXYS1X). The co-occurrence of dystonia and parkinsonism in lubag and in other known disorders suggests there may be a common pathogenetic mechanism. Identification of the genetic defect in this family may provide an important clue toward understanding the pathogenesis and pathophysiology of both dystonia and parkinsonism.     

Mediastinal Hodgkin's disease.

A group of five patients with Hodgkin's disease, nodular sclerosing in type, localized to the mediastinum (Stage IA) is reported. We believe that this presentation sometimes known as "granulomatous thymoma," warrants management in a manner somewhat different from that of the more common presentations of Hodgkin's disease. Nodular sclerosing Hodgkin's disease involving only the mediastinum affects a younger age group in whom the disease may be asymptomatic. Making the diagnosis may necessitate a thoracotomy, but an attempt should be made to obtain tissue short of thoracotomy, as by mediastinoscopy. An extensive attempt at surgical extirpation is not necessary because the disease is very radiosensitive and radiocurable. The combination of Stage I Hodgkin's disease, nodular sclerosing in form, limited to the mediastinum favors an excellent prognosis.     

升麻地上部分化学成分研究升麻地上部分化学成分研究

目的 为开发中药升麻(Cimicifuga foetida L.)的地上部分资源,从中寻找新的天然活性成分。方法 利用多种色谱技术进行分离纯化,根据理化性质和现代波谱技术并辅以化学方法进行结构鉴定。结果 从升麻地上部分80%乙醇提取物的乙酸乙酯部分分得5个9,19-环菠萝蜜烷型三萜皂苷和1个甾醇苷。分别鉴定为:西麻苷I(1),西麻苷II(2),升麻醇半乳糖苷(3),12β-羟基升麻醇木糖苷(4),12β-羟基升麻醇阿拉伯糖苷(5),胡萝卜苷(6)。结论 1和2为新化合物,4及5为首次从该植物中分得。     

端粒酶检测对良恶性腹腔积液鉴别诊断价值的探讨

目的 检测腹腔积液脱落细胞端粒酶活性，探讨端粒酶对良恶性腹腔积液的鉴别诊断价值。方法 运用半定量TRAP-银染法，检测38例恶性腹腔积液和20例良性腹腔积液(对照组)脱落细胞端粒酶活性。结果 肝硬化、结核性腹膜炎腹腔积液脱落细胞检测未发现端粒酶活性，而38例癌性腹腔积液36例(94．7％)端粒酶阳性。所有细胞学检查阳性的恶性腹腔积液端粒酶均为阳性，而3例恶性腹腔积液者，细胞学检查阴性但端粒酶阳性，当复查细胞学检查时，其中1例发现了癌细胞。结论 癌性腹腔积液端粒酶阳性。端粒酶活性的检测对良、恶性腹腔积液有重要鉴别诊断价值，尤其对细胞学检查阴性的病例。     

端粒酶抑制剂对小鼠胃癌放疗的增敏作用研究

目的：探讨端粒酶抑制剂对动物在体肿瘤的治疗作用及对放射治疗的增敏价值。方法：将SGC-7901胃癌细胞接种BALB/c小鼠，采用端粒酶抑制剂AZT联合放疗治疗小鼠胃癌，观察其对肿瘤体积和肿瘤端粒酶活性的影响。结果：未治疗组小鼠肿瘤体积增加了2.5倍，而AZT组、放疗组及AZT联合放疗组肿瘤体积分别缩小了26.3%、36.8%及70.5%。肿瘤端粒酶活性检测，未治疗组、AZT、放疗均能使肿瘤体积缩小并降低前几天粒酶活性分别为100、55.2、24.5及12.1。结论：AZT放疗均能使肿瘤体积缩小并降低端粒酶活性，且AZT能增加肿瘤的放射敏感性。