The effects of formoterol on plasma exudation produced by a localized acute inflammatory response to bradykinin in the tracheal mucosa of rats in vivo.

1. The effects of formoterol, a beta 2-adrenoceptor agonist, on plasma protein exudation and microvascular permeability induced by topical, i.e.

Tryptophan-containing alpha-subunits of the Escherichia coli tryptophan synthase. Enzymatic and urea stability properties.

Early studies suggested that the Escherichia coli tryptophan synthase alpha-subunit unfolded in a two-step process in which there was a stable intermediate composed of a native alpha-1 folding unit (residues 1-188) and a completely unfolded alpha-2 folding unit (residues 189-268). More recent evidence has indicated that such a structure for the intermediate seems unlikely. In this report, single Trp residues (absent in the wild-type alpha-subunit) are substituted separately for Phe residues at positions 139 (in alpha-1) and 258 (in alpha-2) to produce the F139W, F258W, and F139W/F258W mutant alpha-subunits.

Effects of endothelin receptor selective antagonists, BQ-123 and BQ-788, on IRL 1620 and endothelin-1 responses of airway and vascular preparations from rats.

IRL 1620 (Suc-[Glu9, Ala11,15]ET-1(8-21), a selective ETB receptor agonist) contracted rat trachea and bronchus. The maximum response to IRL 1620 was less than that to endothelin-1 (ET-1) and, compared with ET-1 responses, IRL 1620 responses reached equilibrium more quickly. IRL 1620 responses were antagonized by the selective ETB antagonist, BQ-788 (3 microM), but not by the selective ETA antagonist, BQ-123 (3 microM).

In vivo targeting of acute myocardial infarction with negative-charge, polymer-modified antimyosin antibody: use of different cross-linkers.

Background: Cell surfaces and intercellular matrixes contain acidic residues, making them negatively charged. Antibodies are basic, positively charged glycoproteins. Therefore the potential for nonspecific ionic interaction exists, which could increase the background activity.

Cytokines regulate IGF binding proteins in the cns.

Growth factor induction is a major component of the response to central nervous system trauma. The insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) are among the molecules induced by injury that have demonstrated neuroprotective actions. Induction of IGFBPs 2, 3, 4 and 5 have been documented following injury and are hypothesized to function in transport or localization of the IGFs to injured cells.

Evidence that nitric oxide from the endothelium attenuates inherent tone in isolated pulmonary arteries from rats with hypoxic pulmonary hypertension.

1. The inherent contractile tone, and its modulation by the endothelium, have been studied in isolated pulmonary artery preparations taken from rats in which pulmonary hypertension was induced by exposure to a hypoxic environment (10% O2) for 14 days. Control rats were housed in room air.

Pinacidil-induced relaxation in pulmonary arteries isolated from pulmonary hypertensive and normotensive rats and pre-contracted with different spasmogens.

Vasorelaxant responses to the potassium channel opening drug, pinacidil, were obtained on preparations of pulmonary artery and aorta taken from rats with pulmonary hypertension (induced by chronic hypoxia or monocrotaline) and pre-contracted either submaximally with endothelin-1 (ET-1), PGF2 alpha, U46619 (thromboxane-mimetic) or noradrenaline (NA), or with 80 mM K+. In pulmonary artery, but not aorta, from pulmonary hypertensive rats the maximum relaxant response to pinacidil was increased, when compared with data in control rats, irrespective of the spasmogen used to precontract the tissues. The increase in maximum was associated with relaxation to below the tissue resting baseline and probably reflected the presence of inherent contractile tone in arteries from pulmonary hypertensive rats.

Evaluation of myocardial infarct size before and after reperfusion: dual-tracer imaging with radiolabeled antimyosin antibody.

Unlabelled: Antimyosin antibody is a specific marker of myocardial necrosis that is based on the loss of integrity of the sarcolemmal membrane. Because antimyosin can be labeled with several different radiotracers, gamma imaging performed with antimyosin labeled with two different radionuclides can be used to quantify infarct size before and after an intervention such as reperfusion.

Methods: Twelve open-chested anesthetized dogs were evaluated both at the end of 1.

Human immunoglobulin transgenes undergo rearrangement, somatic mutation and class switching in mice that lack endogenous IgM.

We have generated transgenic mice that contain human-sequence Ig miniloci and, because they are also homozygous for a targeted disruption of their endogenous heavy chain genes, must rely on the transgene sequences for B cell receptor expression. Although the human transgenes contain only a fraction of the intact human heavy chain locus, these defined sequences are able to at least partially restore the humoral immune system in the mouse. B cells expressing human heavy chains develop in the bone marrow, populate peripheral lymphoid tissue and respond specifically to antigen.

Evaluation of "Gastromiro" for bowel opacification during computed tomography: comparison with diatrizoate and barium sulphate.

A new oral formulation of iopamidol, "Gastromiro", was evaluated as a bowel contrast agent during abdominal computed tomography (CT). Comparison was made with the well established agents sodium/meglumine diatrizoate ("Urografin 370") and dilute barium sulphate ("E-Z CAT") in a randomized, blind study of 150 consecutive patients undergoing abdominal and/or pelvic CT. Parameters assessed included quality of bowel opacification, artefact generation, contrast-medium palatibility, side effects and cost.

Reduced relaxant potency of nitroprusside on pulmonary artery preparations taken from rats during the development of hypoxic pulmonary hypertension.

1. Relaxant responses to nitroprusside were examined on U46619-contracted pulmonary artery ring preparations from rats exposed to hypoxia, in chambers containing 10% oxygen, for 1, 3, or 14 days, or for 14 days followed by 12 days in room air. Control rats were housed in room air.

Safety and immunogenicity in North Americans of a single dose of live oral cholera vaccine CVD 103-HgR: results of a randomized, placebo-controlled, double-blind crossover trial.

We conducted a double-blind, placebo-controlled, randomized crossover study to evaluate the safety and immunogenicity of a single 5 x 10(8)-CFU dose of live oral recombinant cholera vaccine CVD 103-HgR in 94 North American adults. The vaccine was well tolerated without associated adverse reactions. Despite minimal fecal excretion of vaccine, 97% of subjects exhibited serum vibriocidal antibody and 72% had antitoxin responses.

Posterior cruciate condylar total knee arthroplasty. Average 11-year follow-up evaluation.

Forty-two total knee arthroplasties (TKAs) of the posterior cruciate condylar design performed from 1975 until 1978 were reviewed. Follow-up evaluations averaged 11 years. There were 21 knees each of osteoarthrosis and rheumatoid arthritis.

Dopamine and adrenaline, but not isoprenaline, are substrates for uptake and metabolism in isolated perfused lungs of rats.

The uptake and subsequent metabolism by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) of dopamine, adrenaline, isoprenaline and noradrenaline in isolated perfused lungs of rats has been examined. In lung preparations in which COMT and MAO were inhibited, the uptake of 3H-labelled dopamine, (-)-adrenaline and (-)-noradrenaline, but not (+/-)-isoprenaline, was reduced by cocaine (10 or 100 mumol/l). The rank order of the Km values of the amines that were substrates for uptake in the lungs were: dopamine (0.

Targeted accumulation of polyethylene glycol-coated immunoliposomes in infarcted rabbit myocardium.

The less than optimal accumulation of immunoliposome-associated reagents at target sites has often been attributed to the rapid in vivo clearance of immunoliposomes from the blood. In an attempt to overcome the drawback of rapid clearance and use the targeting potential of immunoliposomes, we have prepared long-circulating, 111In-labeled immunoliposomes. Targeting properties and enhanced circulation times were demonstrated in a rabbit model of acute experimental myocardial infarct.

Vascular uptake of catecholamines in perfused lungs of the rat occurs by the same process as Uptake1 in noradrenergic neurones.

The aim of the study was to determine whether the uptake process for catecholamines in rat lungs is Uptake1, Uptake2 or a distinct process with some properties of both Uptake1 and Uptake2. The initial rate of uptake of noradrenaline was measured in isolated lungs of rats perfused with 2 nmol/l 3H-(-)-noradrenaline for 2 min with monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) inhibited, in the absence or presence of drugs that are substrates or inhibitors of Uptake1 or Uptake2 or of alterations in the ionic composition of the Krebs solution. The rank order of the IC50 values for inhibition of uptake of noradrenaline in the lungs by drugs that are substrates or inhibitors of Uptake1 or Uptake2 is compatible with the conclusion that uptake of catecholamines in rat lungs occurs by Uptake1, and not by a process with the properties of Uptake2.

Responses to vasodilator drugs on pulmonary artery preparations from pulmonary hypertensive rats.

1. Relaxant responses to six vasodilator drugs, with different mechanisms of action, were examined on noradrenaline (0.1 microM)-contracted ring preparations of pulmonary artery and aorta taken from rats with pulmonary hypertension induced by monocrotaline or chronic hypoxia.

Targeting of macromolecular carriers and liposomes by antibodies to myosin heavy chain.

Macromolecular carriers and liposomes were covalently coupled to monoclonal antibodies against cardiac myosin heavy chain. Deferoxamine-modified polymers bound tightly with 67Ga and 68Ga radioisotopes. Ternary deferoxamine-polylysine antibody conjugates specifically targeted the radioisotopes to a myosin-coated microplate.

A voluntary serosurvey and behavioral risk assessment for human immunodeficiency virus infection among college students.

The authors conducted a voluntary serosurvey and educational campaign among 3394 undergraduate students attending the University of Maryland at College Park to determine the prevalence of and risk factors for human immunodeficiency virus type 1 (HIV-1) infection. Two students were seropositive (0.06%, 95% confidence interval 0-0.

Endothelin-induced contractions of rat pulmonary artery are not affected by drugs acting on potassium channels.

The effects of the potassium channel opening drug, pinacidil, and the potassium channel closing drug, tetraethylammonium (TEA), on concentration-response (contraction) curves to spasmogens on rat pulmonary artery were examined. Pinacidil (3 microM) decreased, and TEA (2 mM) increased contractions to 5-hydroxytryptamine (5-HT) more than it did to noradrenaline but contractions to endothelin-1 were only minimally affected. It is concluded that the mechanism whereby endothelin-1 contracts rat pulmonary artery differs from that of noradrenaline or 5-HT in that it does not involve membrane depolarization or calcium entry through voltage operated calcium channels.

Gamma imaging with negatively charge-modified monoclonal antibody: modification with synthetic polymers.

Antimyosin Fab has been modified to carry highly negatively charged synthetic polymers containing DTPAs (DTPA-PL) as chelating agents, of starting molecular weights 3.3 and 17 kD. The immunoreactivities of the modified antibodies were unaffected by the modification procedure.

Attenuation of bradykinin-induced mucosal inflammation by topical budesonide in rat trachea.

The extravasation of plasma proteins and formation of interendothelial gaps in submucosal microvessels by mucosally-applied bradykinin (BK), were studied in the rat trachea. The effects of topical and systemic (s.c.