CNP-induced changes in pHi, cGMP/cAMP and mRNA expression of natriuretic peptide receptors in human trabecular meshwork cells.

It has been demonstrated that natriuretic peptides lower intraocular pressure, however, the underlying cellular mechanism(s) mediating this response remain(s) to be determined. The purpose of this study was to investigate the effects of C-type natriuretic peptide (CNP) on pH(i), cGMP/cAMP and expression of atrial natriuretic peptide receptor (NPR-A), brain natriuretic peptide receptor (NPR-B) and C-type natriuretic peptide receptor (NPR-C), in HTM cells. At concentrations of 10(-7) M, CNP caused an acidification of pH(i). In addition, CNP caused a dose-dependent increase in cGMP formation and inhibition of forskolin-stimulated cAMP accumulation. These changes were not significantly altered in the absence of 10(-3) M isobutylmethylxanthine (IBMX). Treatment with the NPR-A antagonist, anantin, produced no influence on basal cGMP/cAMP levels, the CNP-stimulated cGMP accumulation and CNP-induced inhibition of forskolin-stimulated cAMP accumulation. However, CNP-induced reduction of forskolin-stimulated cAMP accumulation was inhibited by pretreatment with pertussis toxin (PTX). Furthermore, NPRB receptors were predominantly expressed and pretreatment with CNP (10(-7) M, 24hr) enhanced all NPR mRNAs expression which was not altered by higher concentrations or longer incubation. Results demonstrate that NPR-A, NPR-B and NPR-C receptors' expression can be up-regulated by CNP treatment. CNP activates NPR-B receptors preferentially to increase cGMP accumulation and acts through the PTX-sensitive cAMP-signaling pathway leading to a decrease in pH(i).     

The synthesis and antibacterial activities of quinolones containing five- and six-membered heterocyclic substituents at the 7-position

A series of 6-fluoro-7-substituted-1-ethyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acids were prepared. The substituents at the 7-position included five- and six-membered heterocyclic rings such as oxazoline and oxazine as well as five-membered heteroaromatic rings such as oxazoles and imidazoles. The structure--activity relationships (SAR) of these compounds indicated that oxazole substituents containing a 2-methyl group had the greatest in vitro potency. The compounds showed greater in vitro antibacterial activity against Gram-positive organisms than against Gram-negative organisms.     

经左颈静脉肝内门腔静脉支架分流术（附12例报告）

为解决肝硬变门脉高压患者在经颈静脉肝内门腔静脉支架分流术中右颈静脉窄或闭的难题，我们做了经左颈静脉途径完成肝内门腔分流术的尝试。自１９９３年７月至１９９５年８月，共１７８例ＴＩＰＳＳ操作中发现１２例右颈静脉狭窄或闭塞。其方法为经左颈内静脉穿刺、插管入路。     

Tissue distribution metabolism and excretion of 2,2′,4,4′, 5-pentachlorodiphenyl ether in the rat

The tissue distribution, metabolism and excretion of ¹⁴C-2,2,4,4,5-pentachlorodiphenyl ether (PCDE) were studied in the rat. Radioactivity was distributed in all tissues examined, with the highest concentrations being found in the fat followed by the skin, liver, kidney and muscle. Most of the radioactivity found in the tissues was due to unchanged PCDE. Decay of PCDE in the blood was fitted to a four-compartment pharmacokinetic model, and the last compartment had a half-life of 5.8 days. A total of 55% and 1.3% of an orally administered dose was excreted in feces and urine, respectively, in 7 days. More than 64% of the fecal radioactivity was due to unchanged PCDE, while hydroxylated PCDE accounted for 23%.     

二氧化硅活化巨噬细胞中早期生长反应因子-1及其信号转导通路的研究

目的 探讨早期生长反应因子(Egr-1)及其信号转导在矽肺发生发展中的作用。方法用细胞免疫荧光、原位杂交方法检测二氧化硅(SiO2)刺激后Egr-1的表达定位,用报道质粒及EMSA检测其活性改变;用激酶活性分析法检测si0：刺激巨噬细胞后ERK1／2活性改变,进一步用激酶抑制剂初步探讨SiO2活化Egr-1的信号转导通路。结果SiO2刺激RAW264．7细胞短时间Egr-1核蛋白表达及转录因子明显增加;且在处理后30～60min,Egr-1核蛋白结合活性明显升高(为未处理组的20倍);在刺激后15min ERK1／2活性开始升高,30min达高峰(活性为对照组的29倍)而后渐降至基础水平;进一步用激酶阻断发现,Egr-1 mRNA及蛋白表达均减少。结论SiO2能激活巨噬细胞中Egr-1,且此过程可能由ERK1／2、p38介导,提示SiO2-ERK1／2、p38-Egr-1通路可能在矽肺发生发展过程中起重要作用。     

Unusual cardiac papillary fibroelastoma in the right ventricular outflow tract.

Cardiac papillary fibroelastoma (CPF) is the second most common benign neoplasm of the heart. This study describes the case of an 81-year-old man who was admitted to the hospital for severe vertigo and in whom a tumor at the right ventricular outflow tract (RVOT) was identified incidentally during echocardiography. The CPF was excised smoothly following the confirmation of its position by computed tomography. The comprehensive pathologic findings of CPF were reviewed. Detailed immunohistochemical analyses of CD34 and factor VIII-related antigen were performed on the covering endocardial cells. The unique chondroid metaplasia of fibrous tissue in this CPF has never been reported. This work is the first to present an unusual CPF at the RVOT with reactive process of fibrous connective tissue.     

Influence of zinc on Pseudomonas aeruginosa susceptibilities to imipenem.

Serial dilution susceptibility testing of imipenem against 59 clinical isolates of Pseudomonas aeruginosa, conducted simultaneously on single lots of Difco and BBL Mueller-Hinton agar (MHA), resulted in MICs for 90% of strains tested of 8 and 16 micrograms/ml, respectively. MICs for Escherichia coli, Klebsiella pneumoniae, and Pseudomonas spp. were also higher on BBL MHA. Quantification of the cation content of the two MHAs by atomic absorption spectroscopy demonstrated that the zinc concentration in BBL MHA was 15 times greater than that measured in Difco MHA (2.61 and 0.17 micrograms/ml, respectively). Concentrations of calcium, magnesium, iron, manganese, and copper in the two agars were similar. Addition of zinc to Difco MHA resulted in increases in MICs of imipenem for P. aeruginosa but not in the MICs of ceftazidime or cefpirome for P. aeruginosa (P < 0.01). A lesser zinc effect was seen on the activity of imipenem against E. coli, K. pneumoniae, and Pseudomonas spp. The activities of ceftazidime and cefpirome were similar on both MHAs when tested against all gram-negative organisms in this study. Thus, the effect of zinc in MHA was clearly demonstrated by a significant increase in the MICs of imipenem for P. aeruginosa, and, to a lesser extent, for other gram-negative bacilli.     

Urothelial carcinoma of the urinary bladder with a component of acinar/tubular type differentiation simulating prostatic adenocarcinoma

We report a case of an 83-year-old man with a high-grade carcinoma of the urinary bladder who underwent cystoprostatectomy. The invasive carcinoma showed mixed, morphologically distinct patterns consisting of conventional high-grade urothelial carcinoma, glandular differentiation resembling enteric type adenocarcinoma, and acinar/tubular type differentiation, morphologically similar to Gleason grade 3 prostatic adenocarcinoma. Immunohistochemical studies revealed the acinar/tubular component of the tumor to be negative for prostate-specific antigen and prostatic acid phosphatase, but positive for cytokeratin 7, cytokeratin 20, high molecular weight cytokeratin (34 beta E12), and thrombomodulin, consistent with origin from the bladder rather than the prostate. Although bladder carcinomas composed of mixed morphologic patterns are not uncommon, to our knowledge, the presence of acinar/tubular type features simulating prostatic adenocarcinoma in such tumors has not been described elsewhere.     

Further studies on the immunogenicity of Haemophilus influenzae type b and pneumococcal type 6A polysaccharide-protein conjugates

Conjugates were prepared by carbodiimide-mediated coupling of adipic acid hydrazide derivatives of Haemophilus influenzae type b (Hib), Escherichia coli K100, and pneumococcal 6A (Pn6A) polysaccharides with tetanus toxoid (TT), as an example of a “useful” carrier, and horseshoe crab hemocyanin (HCH), as an example of a “nonsense” carrier. These conjugates were injected into NIH mice, and their serum antibody responses to the polysaccharides and proteins were characterized. As originally reported, Hib conjugates increased the immunogenicity of the capsular polysaccharide and elicited greater than the estimated protective levels of anti-Hib antibodies in most recipients after one injection and in all after the third injection (Schneerson et al., J. Exp. Med. 152:361-376, 1980). Both Hib conjugates induced similar anti-Hib responses. The K100-HCH conjugate was more immunogenic than the K100-TT conjugate and elicited anti-Hib responses similar to the Hib conjugates after the third injection. Simultaneous injection of the K100 and the Hib conjugates did not enhance the anti-Hib response. The Pn6A-TT conjugate induced low levels of anti-Hib antibodies; when injected simultaneously with the Hib conjugates, the anti-Hib response was enhanced, as all mice responded after the first injection and with higher levels of anti-Hib than observed with the Hib conjugates alone (P < 0.05). The Pn6A conjugates were not as immunogenic as the Hib conjugates. Pn6A-TT was more effective than was Pn6A-HCH; it elicited anti-Pn6A (>100 ng of antibody nitrogen per ml) in 6 of 10 mice after the third injection. The addition of the Hib-HCH conjugate to the Pn6A-TT conjugate increased the anti-Pn6A response with a higher geometric mean antibody titer, and 9 of 10 mice responded after the third injection. A preparation of diphtheria toxoid, TT, and pertussis vaccine increased the anti-Hib antibody levels after the first injection only in mice receiving Hib-TT, but not in mice receiving Hib-HCH, suggesting that additional carrier protein (TT) enhanced the anti-polysaccharide response. Simultaneous injection of Hib and Pn6A conjugates with the same or different carriers resulted in an enhanced serum antibody response to each polysaccharide. The anti-tetanus toxin response reached protective levels (>0.01 U/ml) in most mice after the first injection and in all mice after the second and third injections of TT conjugates. A progressive increase in the anti-HCH response with each additional injection was noted in animals receiving HCH conjugates. Animals receiving the diphtheria toxoid-TT-pertussis vaccine preparation responded with a greater increase in anti-carrier antibody than those receiving the conjugates alone. This method of synthesis provided conjugates capable of inducing protective levels of antibodies to both the polysaccharides and carrier proteins.     

大鼠中缝大核突触囊泡在电针后的变化及其图象分析

应用透射电镜和图象分析方法,对电针后大鼠中缝大核突触前终扣内突触囊泡的数量以及突触前终扣内容物的量的变化进行了研究。结果表明:电针后,中缝大核突触前终扣内圆形清亮囊泡和颗粒囊泡的数量明显减少,突触囊泡聚集并向突触活性带集中。图象分析结果:电针后,突触前终扣内容物的量较对照组明显减少,而且内容物分布不均匀并在突触膜附近集中。本实验为针刺镇痛的理论研究提供了形态学依据。