It has long been speculated that porcine cathelin is an N-terminal fragment of a longer precursor protein which possesses antimicrobial activity. In an attempt to find such a precursor, a cDNA clone was recently isolated and sequenced by screening a cDNA library from porcine bone marrow. In order to identify the functional activity of the putative protein encoded by an open reading frame, we have synthesized various lengths of peptides that correspond to the C-terminal region of the protein and examined them for their antimicrobial activities. We found that a 13 amino acid tryptophan-rich region with the sequence of VRRFPWWWPFLRR had strong antimicrobial activity with a wide spectrum. It showed potency against Escherichia coli, Pseudomonas aeruginosa, Kiebsiella pneumonia, Staphylococcus epidermidis, Proteus mirabilis, and Streptococcus group D as well as Aspergillus fumigatus. The action of this peptide is bactericidal rather than bacteriostatic and this activity is completely inhibited by 2 mM MgC12. Our results indicate that the previously identified putative precursor encoded by the isolated cDNA indeed possesses a potent antimicrobial activity and that this 13 amino acid synthetic peptide is considered to be a potentially effective drug against various infections agents.

The CorA transport system is the primary Mg2+ influx system of Salmonella typhimurium and Escherichia coli. The CorA protein has no homology to any other known family of proteins. It has an unusual membrane topology, with a large, soluble, highly charged periplasmic N-terminal domain with three transmembrane segments in a shorter, hydrophobic C-terminal domain. Previous phenotypic and molecular data had suggested that this transport system was widespread in the Bacteria. In this report we show that CorA is virtually ubiquitous in the Bacteria and Archaea, forming a distinct family of transport proteins. Genomic sequences to date have revealed at least 22 members of the CorA family in the Bacteria and the Archaea, with 6 more distant members in the yeasts. Only three of the smallest bacterial genomes lack a CorA homologue. Strikingly, phylogenetic analysis does not show clustering by related species or even within kingdom. Several species of Bacteria contain two or even three CorA paralogues. Within species, these paralogues are not closely related, however, and we suggest that they might have distinct transport functions. A multiple alignment suggests three extended consensus regions within the N-terminal soluble domain of CorA, which is predicted to be virtually all alpha-helical. A fourth consensus region includes the last 20 residues of the soluble domain and continues through the entire membrane domain. The first half of this last consensus domain may form an amphipathic alpha-helix that extends from the soluble domain into the first transmembrane segment. The degree of charge in the first transmembrane segment is quite variable, and we suggest that this transport family may include members with only two rather than three transmembrane segments. If so, this would place the N-terminal soluble domain on different sides of the membrane in different members of the family. We suggest that the CorA Mg2+ transport system forms the major Mg2+ uptake system in the Bacteria and Archaea but that some family members may have a function other than Mg2+ transport.

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A polyhydroxy alkaloid has been isolated from the seeds of the African legume Angylocalyx pynaertii and identified as a 2-hydroxymethyl-3,4-dihydroxy-5-methylpyrrolidine by ms and 1H- and 13C-nmr spectroscopy. The absolute stereochemistry was established, by a stereochemically unambiguous synthesis from diacetone glucose, as 2,5-imino-1,2,5-trideoxy-D-mannitol, which may also be regarded as 2R,5R-dihydroxymethyl-3R,4R-dihydroxypyrrolidine (DMDP) [2] in which a hydroxymethyl group is deoxygenated, i.e., 6-deoxy-DMDP [1]. Whereas the structurally related polyhydroxypyrrolidine alkaloids which have previously been discovered are inhibitors of alpha- and beta-glucosidase, 6-deoxy-DMDP is unique in inhibiting beta-mannosidase. In addition to this novel alkaloid and 2-hydroxymethyl-3,4-dihydroxypyrrolidine [3], previously shown to be present in several Angylocalyx species, the known piperidine alkaloids deoxymannojirimycin [4] and fagomine [5] were identified for the first time as constituents of An. pynaertii seeds.

One hundred forty-one patients were prospectively enrolled in a study of contact-tip laser bullectomy at four institutions. Ninety-one have had both preoperative and postoperative testing at 3 months. Nonsmoking patients with disabling dyspnea at less than 50 yards and with a forced expiratory volume in 1 second of 35% or less were enrolled. Testing included formal pulmonary function tests, arterial blood gasses, computed tomographic scans, ventilation/perfusion scans, echocardiograms, electrocardiograms, 6-minute walk testing, transdiaphragmatic pressures, and quality of life and dyspnea index questionnaires. A modest 16% improvement was noted in forced expiratory volume in 1 second (0.69 to 0.80 L), and there was a 29% improvement in 6-minute walk distances (655.2 to 846.3 feet). Oxygen use was completely discontinued in 16%. Risk factors for mortality included age, 6-minute walk distances, low diffusing capacity for carbon monoxide, high carbon dioxide tension, and high base excess. Minor improvement was judged from the dyspnea index and the Medical Outcome Study Short Form-36. Preoperative predictors of good outcome included heterogeneous disease, lack of carbon dioxide retention, and no emaciation (weight < 40 kg). Comparison of our results with those in the literature suggests that the improvement seen with the contact neodymium:yttrium-aluminum-garnet laser is not as good as that provided by the stapled techniques for volume reduction.