Correlation of CT findings with clinical evaluations in 261 patients with symptomatic bronchiectasis.

Objective: In a multicenter study, we evaluated the relationships between the extent and severity of bronchiectasis on CT and clinical symptoms, spirometric abnormality, and sputum characteristics.

Subjects And Methods: The study population included 261 patients with symptomatic, physiologically significant bronchiectasis, who were enrolled in another study evaluating the clinical efficacy of deoxyribonudease in treatment of bronchiectasis. Patients with cystic fibrosis, allergic bronchopulmonary aspergillosis, and fungal or mycobacterial infection were excluded.

The crystal structure of a bacterial, bifunctional 5,10 methylene-tetrahydrofolate dehydrogenase/cyclohydrolase.

The structure of a bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase/cyclohydrolase from Escherichia coli has been determined at 2.5 A resolution in the absence of bound substrates and compared to the NADP-bound structure of the homologous enzyme domains from a trifunctional human synthetase enzyme. Superposition of these structures allows the identification of a highly conserved cluster of basic residues that are appropriately positioned to serve as a binding site for the poly-gamma-glutamyl tail of the tetrahydrofolate substrate.

Phase variation of HpuAB and HmbR, two distinct haemoglobin receptors of Neisseria meningitidis DNM2.

We have previously described HpuAB, a two-component receptor that mediates binding to haemoglobin (Hb), haemoglobin-haptoglobin (Hb-Hp) and apo-haptoglobin (Hp). In this communication, we constructed non-polar mutations in the hpuA and hpuB loci to examine the individual roles of HpuA and HpuB. Our results indicate that both HpuA and HpuB are required for the acquisition of Fe from Hb and Hb-Hp.

Risk factors for infection with Toxoplasma gondii for residents and workers on swine farms in Illinois.

Risk factors for Toxoplasma gondii infection in workers and residents of swine farms were studied on 43 farms in Illinois. Blood samples were collected from 174 adults in 1993. The T.

Germination responses and boron accumulation in germplasm from Chile and the United States grown with boron-enriched water.

Boron (B) is toxic to most plant species when accumulated in high concentrations. Differences in a plant's ability to adapt to high concentrations of B may depend on the origin of the germplasm. Chilean and domestic (U.

Antithrombotic efficacy of thrombin inhibitor L-374,087: intravenous activity in a primate model of venous thrombus extension and oral activity in a canine model of primary venous and coronary artery thrombosis.

The small molecule direct thrombin inhibitor L-374,087 was characterized across species in an in vitro activated partial thromboplastin clotting time (aPTT) assay and in vivo in rhesus monkey and dog thrombosis models. In vitro in rhesus, dog, and human plasma, L-374,087 concentrations eliciting 2-fold increases in aPTT were 0.25, 1.

L-374,087, an efficacious, orally bioavailable, pyridinone acetamide thrombin inhibitor.

Replacement of the amidinopiperidine P1 group of 3-benzylsulfonylamino-6-methyl-2-pyridinone acetamide thrombin inhibitor L-373,890 (2) with a mildly basic 5-linked 2-amino-6-methylpyridine results in an equipotent compound L-374,087 (5, Ki = 0.5 nM). Compound 5 is highly selective for thrombin over trypsin, is efficacious in the rat ferric chloride model of arterial thrombosis and is orally bioavailable in dogs and cynomolgus monkeys.

Biotin uptake by human colonic epithelial NCM460 cells: a carrier-mediated process shared with pantothenic acid.

Previous studies showed that the normal microflora of the large intestine synthesizes biotin and that the colon is capable of absorbing intraluminally introduced free biotin. Nothing, however, is known about the mechanism of biotin absorption in the large intestine and its regulation. To address these issues, we used the human-derived, nontransformed colonic epithelial cell line NCM460.

Transport of intact porphyrin by HpuAB, the hemoglobin-haptoglobin utilization system of Neisseria meningitidis.

The meningococcal hemA gene was cloned and used to construct a porphyrin biosynthesis mutant. An analysis of the hemA mutant indicated that meningococci can transport intact porphyrin from heme (Hm), hemoglobin (Hb), and Hb-haptoglobin (Hp). By constructing a HemA- HpuAB- double mutant, we demonstrated that HpuAB is required for the transport of porphyrin from Hb and Hb-Hp.

Efficacious, orally bioavailable thrombin inhibitors based on 3-aminopyridinone or 3-aminopyrazinone acetamide peptidomimetic templates.

We have addressed the key deficiency of noncovalent pyridinone acetamide thrombin inhibitor L-374,087 (1), namely, its modest half-lives in animals, by making a chemically stable 3-alkylaminopyrazinone bioisostere for its 3-sulfonylaminopyridinone core. Compound 3 (L-375,378), the closest aminopyrazinone analogue of 1, has comparable selectivity and slightly decreased efficacy but significantly improved pharmacokinetics in rats, dogs, and monkeys to 1. We have developed an efficient and versatile synthesis of 3, and this compound has been chosen for further preclinical and clinical development.

Testing a new alcohol-free hand sanitizer to combat infection.

Universal precautions require that perioperative health care personnel wash their hand before and after all patient contact. Time constraints, however, can make adhering to universal precautions, including proper hand washing, difficult. Some perioperative health care workers, therefore, routinely use rise-free hand sanitizers to supplement normal hand washing.

Identification and molecular analysis of lbpBA, which encodes the two-component meningococcal lactoferrin receptor.

We identified lbpB, encoding the lipoprotein component of the meningococcal lactoferrin receptor. An LbpB mutant was unable to acquire Fe from lactoferrin and exhibits decreased surface binding to lactoferrin. Primer extension and reverse transcription-PCR analysis indicate that lbpB and lbpA are cotranscribed on a polycistronic Fe-repressible mRNA.

Pharmacological characterization of alpha-adrenoceptors in the bovine median caudal artery.

This study was initiated to characterize alpha-adrenoceptors in the isolated bovine median caudal (tail) artery preparation for use as a model of blood vessels in the extremities of cattle. Prazosin shifted the concentration-response relationship for noradrenaline and phenylephrine to the right with pA2 values of 8.74 and 9.

Analysis of the alcABC operon encoding alcaligin biosynthesis enzymes in Bordetella bronchiseptica.

We previously cloned a B. bronchiseptica (Bb) genomic DNA fragment that complements a Bb alcaligin biosynthesis mutant, and reported the identification of a gene, alcA, with predicted protein sequence similarity to siderophore biosynthesis enzymes from other organisms. In the present study we show that further nt sequencing of this region revealed two open reading frames (ORFs) 3' to alcA that encode putative proteins AlcB and AlcC, with significant sequence similarity to the aerobactin biosynthesis enzymes IucB and IucC, respectively.

Heterogeneity and complexity of alpha 1-adrenoceptors in the ovine uterine artery and umbilical vein.

To understand the subtypes of alpha 1-adrenoceptors in the regulation of uterine and umbilical vascular function, the subtypes of alpha 1-adrenoceptors in the ovine uterine artery and umbilical vein were investigated pharmacologically. The use of the irreversible alpha 1B-adrenoceptor antagonist, chloroethylclonidine, revealed the heterogeneity of alpha 1-adrenoceptors in these two tissues. Chloroethylclonidine showed different patterns of action.

5-Hydroxytryptamine stimulates phosphoinositide hydrolysis and contraction in the ovine umbilical artery.

5-Hydroxytryptamine-stimulated contraction and generation of inositol phosphates (InsPs) were investigated in isolated ovine umbilical artery from near term pregnant sheep. 5-Hydroxytryptamine produced a concentration-dependent contraction in the presence or absence of external Ca2+, however, the contractile response in Ca(2+)-free medium was depressed by 67% (P < 0.05).

Human intestinal folate transport: cloning, expression, and distribution of complementary RNA.

Background & Aims: Despite intensive investigations, very little is known about the molecular identity(ies) of the intestinal folate transport system(s), especially in humans. The aim of this study was to isolate a functional human intestinal folate carrier complementary DNA (cDNA) clone and determine the distribution of complementary RNA at the tissue and cellular levels.

Methods: Hybridization screening, modified Marathon cDNA amplification, expression in Xenopus oocytes, Northern analysis, and in situ hybridization were used.

Molecular characterization of hpuAB, the haemoglobin-haptoglobin-utilization operon of Neisseria meningitidis.

We previously identified HpuB, an 85 kDa Fe-repressible protein required for utilization of Fe from, and binding to, haemoglobin and the haemoglobin-haptoglobin complex. The gene for hpuB was cloned from Neisseria meningitidis strain DNM2 and the predicted amino acid sequence indicates that HpuB is an outer membrane receptor belonging to the TonB family of high-affinity transport proteins. A second open reading frame, predicted to encode a 34.

Purification, crystallization, and preliminary x-ray studies of a bifunctional 5,10-methenyl/methylene-tetrahydrofolate cyclohydrolase/dehydrogenase from Escherichia coli.

A bifunctional enzyme that catalyzes the conversion of formyltetrahydrofolate to methylene-tetrahydrofolate (5,10-methenyltetrahydrofolate cyclohydrolase and 5,10-methylene tetrahydrofolate dehydrogenase), has been subcloned from a cDNA library, purified to homogeneity, and crystallized. The crystals belong to space group I222, with unit cell dimensions of a = 64.5 A, b = 84.

Identification and purification of a hemoglobin-binding outer membrane protein from Neisseria gonorrhoeae.

The majority of in vitro-grown Neisseria gonorrhoeae strains were unable to use hemoglobin as the sole source of iron for growth (Hgb-), but a minor population was able to do so (Hgb+). The ability of Hgb+ gonococci to utilize hemoglobin as the iron source was associated with the expression of an iron-repressible 89-kDa hemoglobin-binding protein in the outer membrane. The N-terminal amino acid sequence of this protein revealed amino acids, from positions 2 to 16, identical to those of HpuB, an 85 kDa iron-regulated hemoglobin-haptoglobin utilization outer membrane protein of Neisseria meningitidis.

Cloning and characterization of the Actinobacillus actinomycetemcomitans gene encoding a heat-shock protein 90 homologue.

In a search for clones from a lambda gt11 expression library of Actinobacillus actinomycetemcomitans (Aa) genomic DNA that expressed epitopes from a 70-kDa iron-repressible membrane protein, we inadvertently identified clones that encoded a member of the 90-kDa heat-shock protein (HSP 90) family. The gene appears to encode a homologue of HtpG, as the nucleotide sequence has approximately 70% identity with the Escherichia coli (Ec) and Vibrio fischeri htpG. Growth of an Aa htpG insertion mutant at 42 degrees C was reduced to 50% of the parent strain, similar to an Ec htpG deletion mutant.