trans-2-Aryl-N,N-dipropylcyclopropylamines: synthesis and interactions with 5-HT(1A) receptors

Twelve N,N-dipropyl-substituted derivatives of trans-2-arylcyclopropylamine have been prepared and assayed for their ability to displace [(3)H]-8-OH-DPAT from rat brain 5-HT(1A) receptors. The new derivatives include phenyl (7a), bromo- (7b) and fluorophenyl (7c-e), 2-methoxy-5-fluorophenyl (7h), and 2-hydroxy-5-fluorophenyl (7l) as well as trifluoromethylphenyl (7f) and 2,3-dichlorophenyl (7g) analogues. In the present series of compounds, electron-withdrawing substituents in the phenyl ring appear to decrease the affinity for 5-HT(1A) receptors. In contrast, electron-rich aryl groups, such as 2- or 3-thienyl (7j and 7k, respectively), provide compounds with high affinity. The additional bulk produced by the aromatic moiety in the 2-benzothienyl derivative 7i appears to be detrimental to 5-HT(1A) receptor affinity. The racemic mixtures of the interesting 7j and 7l were resolved into the enantiomers; 7j and 7l exhibited a high enantiomeric 5-HT(1A) receptor affinity ratio (75-fold and 100-fold, respectively). The enantiomers of 7j and 7l were evaluated in vivo by use of biochemical and behavioral tests in rats. Compound (1R,2R)-7j behaved as a partial agonist whereas (1R,2S)-7l appeared as an efficacious 5-HT(1A) receptor agonist, stimulating both autoreceptors and postsynaptic receptors.     

Cloning, expression and sequence analysis of the SphI restriction-modification system

SphI, a type II restriction-modification (R-M) system from the bacterium Streptomyces phaeochromogenes, recognizes the sequence 5'-GCATGC. The SphI methyltransferase (MTase)-encoding gene, sphIM, was cloned into Escherichia coli using MTase selection to isolate the clone. However, none of these clones contained the restriction endonuclease (ENase) gene. Repeated attempts to clone the complete ENase gene along with sphIM in one step failed, presumably due to expression of SphI ENase gene, sphIR, in the presence of inadequate expression of sphIM. The complete sphIR was finally cloned using a two-step process. PCR was used to isolate the 3' end of sphIR from a library. The intact sphIR, reconstructed under control of an inducible promoter, was introduced into an E. coli strain containing a plasmid with the NlaIII MTase-encoding gene (nlaIIIM). The nucleotide sequence of the SphI system was determined, analyzed and compared to previously sequenced R-M systems. The sequence was also examined for features which would help explain why sphIR unlike other actinomycete ENase genes seemed to be expressed in E. coli.     

Bad ethics, good ethics and the genetic engineering of animals in agriculture

PURPOSE: The purpose of this retrospective study is to compare the measurements of intrapapillary and peripapillary parameters between two observers and test the usefulness of measuring different types of crescents. METHODS: Optic disc photographs of 23 eyes of 23 patients with glaucoma and 23 age-matched normal eyes were measured in Oulu and in Erlangen using manual planimetric techniques. The authors measured the following magnification corrected intrapapillary and peripapillary areas: optic disc, neuroretinal rim, cup: disc area ratio, scleral ring, central (zone beta), and peripheral peripapillary atrophy (zone alpha). Twenty-one patients with glaucoma had a follow-up of 3.2 years (range, 1.1-4.7 years), and follow-up for 19 control eyes was 3.7 years (range, 2.5-5.9 years). The measurements were performed in a masked fashion for the diagnosis and temporal sequence of the photographs. RESULTS: Central peripapillary atrophy (zone beta) was statistically significantly largest in primary open-angle glaucoma in both centers (Oulu, P=0.003; Erlangen, P=0.004), whereas normal and exfoliative eyes did not differ significantly from each other. The results for peripheral peripapillary atrophy (zone alpha) and scleral ring were less consistent. Despite statistically significant interobserver correlations ranging from r=0.30 (scleral ring area; P=0.0472) to r=0.97 (optic disc area; P=0.0001), the means of all parameters, except for zone alpha and beta, differed statistically significantly between the two observers. CONCLUSIONS: The central peripapillary atrophy, or zone beta, is the most reproducible parameter when measuring peripapillary atrophy in glaucoma. Nonetheless, its measurement is of limited usefulness in the recognition of glaucoma or progression of glaucomatous nerve damage.     

Follow-up of TIPS: evaluation of signs of dysfunction with Doppler ultrasonography

The anemia of malignancy is common and is related to several etiologic factors, a major one being relative erythropoietin (Epo) deficiency. Blood transfusions, the traditional therapy, provides a quick solution but is associated with complications. This was the rationale for recombinant human Epo (rHuEpo) in the treatment of anemia of cancer. Over the past few years, about 20 publications have reported the results of rHuEpo in the treatment of cancer-associated anemia in more than 850 patients with a variety of malignancies. In general, more than half of the patients responded with a significant increase in their hemoglobin level, a decrease in blood transfusion requirements, and an improved performance status and quality of life. About 4 weeks are required till the onset of effect. The hormone is well tolerated with minimal adverse effects and subcutaneous injections appear to be the preferred method of administration. Additional studies will hopefully answer several questions including optimal dosage and duration of treatment, Epo resistance, and the possibility of predicting the response.     

Maximal utilization of the left internal mammary artery for coronary bypass grafting

A technique is described for using the internal mammary artery to bypass the left anterior descending coronary artery and another adjacent coronary artery even when the alignment of the two vessels is not favorable for a conventional sequential graft. The distal end of the mammary artery is amputated and used to construct a Y graft to the anterior descending artery and to the secondary target vessel.     

Diffuse adherence, ST-I enterotoxin and CFA/IV colonization factor are encoded by the same plasmid in the Escherichia coli O29:H21 strain

Escherichia coli O29:H21 is a human enterotoxigenic serotype that produces heat-stable (ST-I) enterotoxin, adheres diffusely to HeLa cells, and presents colonization factor antigen IV (CFA/IV) composed of CS5CS6 surface antigens. In one strain studied the genes for diffuse adherence and CFA/IV (CS5CS6) production were found to be present in the same plasmid encoding ST-I. The virulence plasmid (Ent) presented two unrelated basic replicons homologous to repFIC and repW. Gene(s) encoding diffuse adherence did not share homology with the probe for F1845 fimbrial adhesin which is responsible for this phenotype in other E. coli strains. Ent plasmids containing genes for diffuse adherence have not been described previously.