Agonist-induced GTPgamma35S binding mediated by human 5-HT(2C) receptors expressed in human embryonic kidney 293 cells

The 5-HT(2C) receptor as heterologously expressed in various mammalian cells mediates inositol 1,4,5-triphosphate (IP(3)) signal by activating G(q/11) subtypes of G proteins, but minimally promotes agonist-induced GTPgamma35S binding in membranes due to slow GTP turnover rates of the G proteins. Here we discovered robust (over 200%) agonist-induced GTPgamma35S binding mediated by the human receptor expressed in human embryonic kidney (HEK) 293 cells, and investigated its pharmacology. Agonists concentration-dependently increased GTPgamma35S binding in isolated membranes, which was competitively blocked by antagonists. Intrinsic efficacies of agonists from GTPgamma35S binding were comparable to those from IP(3) measurement. Pertussis toxin treatment largely blocked serotonin-induced GTPgamma35S binding, serotonin high affinity sites by 70% without altering the total binding sites, and reduced IP(3) release by 40%. GTPgamma35S-bound Galpha subunits from serotonin-activated membranes were mainly Galpha(i), judging from immobilization studies with various Galpha-specific antibodies. Inhibition of forskolin-stimulated cAMP formation, however, was not observed. Apparently, the 5-HT(2C) receptor-mediated GTPgamma35S binding is a unique phenotype observed in HEK293 cells, reflecting its coupling to pertussis toxin-sensitive G(i) subtypes, which contribute to the IP(3) signal, along with pertussis toxin-insensitive G(q/11) subtypes.     

Inducible nitric oxide synthase inhibitors fromMelia azedarach var.Japonica

In bioassay-guided search for inducible nitric oxide synthase (iNOS) inhibitory compounds from higher plants of South Korea, two beta-carboline alkaloids, 4-methoxy-1-vinyl-beta-carboline (1) and 4,8-dimethoxy-l-vinyl-beta-carboline (2) have been isolated from the cortex of Melia azedarach var. japonica. The structures of these compounds were elucidated on the basis of spectroscopic data. Compounds 1 and 2 showed marked inhibitory activity of iNOS on LPS- and interferon-gamma-stimulated RAW 264.7 cells.     

Esters of substituted benzoic acids as anti-thrombotic agents

Aliphatic esters of protocatechuic acid (PA,1), vanillic acid (VA,9) and gallic acid (GA,18) were prepared and their anti-thrombotic effects were evaluated in the mouse model of thrombosis. The aliphatic groups included methyl, ethyl,n-propyl,i-propyl,n-butyl,i-butyl,n-amyl and cyclohexyl.n-Amyl ester of PA (7), i-propyl and cyclohexyl esters of VA (13 and17 respectively) and ethyl ester of GA (20) treatment significantly lowered the death rate and increased the recovery from paralysis due to the thrombotic challenge. From the limited analogs available, it was tentatively concluded that the structural conformation, where carboxy oxygen (=O or-O^?) of the carboxyl group (COOH) at C₁ and the oxygen function at C₃ (either OH or OCH₃) are closely situated, is favorable for the esters of PA, VA and GA to be more antithrombotic.     

Studies on constituents of Korean basidiomycetes (L)

To find antitumor metabolites in Korean basidiomycetes, the shake-cultured mycelia of eight of the higher fungi were extracted with hot water and the extracts, after being partially purified, were subjected toin vivo antitumor test. When administeredi.p. at the dose of 30mg/kg/day for ten consecutive days into the female ICR mice, which had been implanted with 1×10⁵ cells of sarcoma 180 twenty-four hours before the first injection, the extracts ofAgaricus campestris, Lyophyllum decastes, Lyophyllum ulmarium, Armillaria tabescence andCalvatia exipulitormis respectively showed inhibition ratios of 64.1%, 65.4%, 60.0%, 53.0% and 49.3%. These five species were selected for further study, whereas the extracts ofPhallus impudicus, Coprinus comatus andPholiota squarrosa which showed the inhibition ratios of 31.2%, 33.5% and 19.0% were discontinued.     

Studies on corneal penetration ofp-hydroxybenzoic acid esters

Corneal permeability of variousn-alkylp-hydroxybenzoates (parabens) was studiedin vitro using excised rabbit corneas, and the effect of lipophilicity of parabens on the corneal permeability was also investigated. Permeability coefficients were obtained from the least-square linear regression after the steady state had been reached. Lipophilicity of parabens was calculated by distribution coefficients determined in octanol-S \(12_\phi [\kern-0.15em[ \) rensen’s buffer solution (pH 5.0). The relationship between lipophilicity and corneal permeability of parabens was not linear, but the optimum lipophilicity for the maximum permeation was found. The influence of tween 80 on corneal permeability of methyl and butylparaben was not significant.     

Apical opacity associated with pulmonary tuberculosis: high-resolution CT findings

To elucidate the nature of the apical opacity that is commonly seen in patients with tuberculosis--usually referred to as an "apical cap" or "apical pleural thickening"--18 patients with upper lobe tuberculosis were studied with high-resolution computed tomography (HRCT). All had a homogeneous apical opacity at least 1 cm thick on chest radiographs. Fifteen of the 18 had a history of pulmonary tuberculosis of more than 5 years duration, and nine showed evidence of ipsilateral pleurisy. HRCT scans at the apex of the thorax in all nine patients scanned at this level showed that extrapleural fat with interspersed vessels accounted for most of the plain radiographic opacity. Scans obtained at a level slightly above visible aerated lung showed extrapleural fat 3-25 mm thick peripherally and atelectatic lung centrally. At more caudal levels, at which both aerated lung and "thickened pleura" were visible on plain radiographs, HRCT showed extrapleural fat (3-20 mm thick), thickened pleura (1-3 mm thick), and atelectatic lung peripherally and areas of emphysematous bullae, bronchiectasis, and atelectatic lung centrally.     

Pulmonary tuberculosis in five young infants with nursery exposure: clinical, radiographic and CT findings

Clinical, radiographic (n = 5) and CT findings (n = 4) of five Korean infants ranging in age from 2 to 3 months with confirmed tuberculosis were retrospectively analysed. All of the patients were symptomatic, anergic to tuberculin, and had a positive culture of Myobacterium tuberculosis in gastric aspirates. The probable source of infection was the hospital in which they were born. CT scans demonstrated hilar and mediastinal lymph node enlargement with central low attenuation and peripheral enhancement in all cases. CT may be useful in diagnosis by demonstrating characteristic adenopathy and disseminated disease in young infants. Received: 2 September 1997 Accepted: 23 April 1998     

Dynamic contrast-enhanced MR imaging of bacterial abscess and VX2 carcinoma in rabbits: comparison of gadopentetate dimeglumine and a macromolecular contrast agent

OBJECTIVE: The objective of this study was to compare enhancement patterns of a blood-pool contrast agent, Gadomer-17, with those of gadopentetate dimeglumine in bacterial abscesses and VX2 carcinoma in rabbits. MATERIALS AND METHODS: Fourteen rabbits with experimentally induced bacterial abscesses and VX2 carcinoma in both thighs underwent dynamic contrast-enhanced MR imaging with Gadomer-17 and gadopentetate dimeglumine at a 24-hr interval. The enhancement ratios (postcontrast to precontrast signal intensities) of lesions in the same animal were assessed and correlated with microvessel density. RESULTS: For Gadomer-17, the enhancement ratio of the abscesses (1.66 +/- 0.39) peaked 15 min after the injection, while that of the carcinoma (2.05 +/- 0.16) peaked at 10 min. The enhancement ratios of the carcinoma were consistently higher than those of the abscesses up to 30 min. For gadopentetate dimeglumine, peak enhancement ratio of the abscesses (2.30 +/- 0.75) was seen 5 min after the injection, while that of the carcinoma (2.32 +/- 0.51) was seen at 3 min. The enhancement ratios of the carcinomas were significantly higher at 1 min, but significantly lower at 20-30 min, compared with those of the abscesses, as a result of rapid decrease of enhancement ratios in the carcinomas. The microvessel density was 9.8 +/- 5.2 vessels per field of view for the abscesses and 36.3 +/- 9.5 vessels per field of view for the carcinoma (p < 0.001). CONCLUSION: Delayed peak enhancement and slow decay were found in both bacterial abscess and VX2 carcinoma with Gadomer-17, whereas early peak enhancement and rapid decay were found especially in VX2 carcinoma with gadopentetate dimeglumine. Enhancement ratios on MR imaging with a blood-pool contrast agent correlated well with the microvessel density in bacterial abscess and VX2 carcinoma.     

Percutaneous Placement of Self-expandable Metallic Biliary Stents in Malignant Extrahepatic Strictures: Indications of Transpapillary and Suprapapillary Methods

Objective

To compare the efficacy of suprapapillary and transpapillary methods of transhepatic biliary metallic stent placement in malignant biliary strictures and to specify the indications of each method applied.

Materials and Methods

Stents were placed in 59 patients. Strictures were categorized as type A (within 3 cm of the ampulla, n = 27), type B (over 3 cm from ampulla, n = 7), type C (within 3 cm of the bending portion, n = 9), or type D (over 3 cm above the bending portion, n=16). The stenting method was suprapapillary in 34 cases and transpapillary in 25. The rates of initial and long-term patency and of early recurrence were compared.

Results

Initial patency rates for the suprapapillary and transpapillary methods were 1/7 (14.3%) and 20/20 (100%) respectively for type A (p < 0.0001), 4/5 (80.0%) and 2/2 for type B, 3/7 (42.9%) and 2/2 for type C, and 15/16 (93.8%) and 0/0 for type D. Early recurrence rates were 7/30 (23.3%) using the suprapapillary method and 4/29 (13.8%) using the transpapillary method (p = 0.51). The long-term patency rate did not differ significantly according to either type (p = 0.37) or method (p = 0.62).

Conclusion

For good initial patency, the transpapillary method is recommended for strictures of the distal extrahepatic duct near the ampulla and just above the bending portion. Long-term patency is not influenced by the stenting method employed.