Chloride secretion in response to guanylin in colonic epithelial from normal and transgenic cystic fibrosis mice.

1. Guanylin, a 15 amino acid endogenous gut peptide, increased the short circuit current (SCC) in the epithelium of the mouse colon, but only when applied to the apical and not the basolateral surface. 2. By use of selective blockers of epithelial ion transport and modification of the bathing solution, it was concluded that guanylin increased electrogenic chloride secretion but also had a minor effect on electrogenic sodium absorption. In addition there were small residual currents which remained unresolved. 3. The threshold concentration of guanylin causing a SCC increase was less than 50 nM, but at concentrations 40 times greater no indication of a maximally effective concentration was found. 4. Two guanylin isomers with the same amino acid sequence but with the disulphide bridges joined in an alternate fashion showed no activity. Thus only guanylin with the greatest structural homology to heat stable enterotoxin (STa) showed biological activity. 5. The action of guanylin was virtually eliminated in colonic epithelia from transgenic cystic fibrosis (CF) mice. As these animals lack the chloride channel coded by the CF gene sequence, it is likely that the final effector process in murine colonic epithelia involves the CFTR (cystic fibrosis transmembrane conductance regulator) chloride channel. 6. Opportunistic infections of the gut generating STa lead to diarrhoeal conditions via an action of the toxin on apical guanylin receptors. Thus, as discussed, the CF heterozygote may have a genetic advantage in this circumstance.     

人睾丸cDNA文库的构建

本研究从人睾丸组织的总RNA中纯化mRNA,并以此为模板,在AMV反转录酶的作用下,制备互补的SS-cDNA。用RNaseH降解模板mRNA,经DNA多聚酶Ⅰ作用,合成ds-cDNA。用T_4DNA多聚酶制备cDNA的平末端,在T_4DNA连接酶的作用下,连接Ecorl接头并与λgt11载体重组连接,以大肠杆菌Y1090做受体菌转染,构建人睾丸cDNA文库。结果表明cDNA文库构建成功,将对生殖和避孕进一步研究发挥重要的作用。     

3H-1,2-二氢-1-吡里酮衍生物的合成

发现3 H-1,2-二氢-1-吡咯里嗪酮具有明显的抗炎镇痛作用。用Friedel-Crafts酰化和Dieckmann缩合等反应制备了该酮的一些衍生物,其中五个未见于文献报道。药理实验证明,这些化合物均有不同程度的抗炎镇痛作用。     

Pheochromocytoma and the normal adrenal medulla: improved visualization with I-123 MIBG scintigraphy

The radiopharmaceutical iodine 131 metaiodobenzylguanidine (I-131 MIBG) has been shown to locate pheochromocytomas scintigraphically with a false-negative rate of approximately 13%. To improve image quality and reduce the false-negative rate, I-123 was examined as a radioactive label for MIBG, as it has many advantages over I-131, including superior dosimetry and better detection efficiency. Diagnostic doses of 0.5 mCi (18.5 MBq) I-131 MIBG and 10.0 mCi (370.0 MBq) I-123 MIBG with nearly equivalent radiation dosimetries were compared in 18 patients with known or suspected pheochromocytomas. Images of superior quality were obtained with I-123 MIBG in 18 of 18 patients, and in eight cases lesions not visualized on I-131 MIBG scintigraphy were portrayed. A further advantage of I-123 MIBG is that it permits single photon emission computed tomography (SPECT). This was performed in six cases and provided additional information in three cases. The adrenal medullae were definitely visualized using I-123 scintigraphy in eight of 14 patients still possessing adrenal glands, whereas I-131 MIBG images portrayed the adrenal medulla in only one of 14 cases. Five remaining patients had multiple abdominal tumor deposits that were difficult to differentiate from normal adrenal medullae.     

Splenectomy in myeloid metaplasia

Between 1960 and 1977, 50 patients with agnogenic myeloid metaplasia were splenectomized. Twenty-five of 26 patients with painful splenomegaly, 4 of 9 patients with refractory hemolytic anemia, 4 of 10 patients with refractory thrombocytopenia, and 4 of 4 patients with portal hypertension showed significant benefit from the procedure. There were five immediate postoperative deaths. Four of these deaths occurred early in our series of splectomies for myeloid metaplasia before 1970. Only one death has occurred in the last 21 patients operated on. Survival following splenectomy averaged 25.5 mo.