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Biomedical subjects

D J Smith

Publications and source records attributed to D J Smith.

At least 127 records · Page 7Linked to original sources
PubMed1998

Aerosolization of novel nitric oxide donors selectively reduce pulmonary hypertension.

OBJECTIVES: Inhaled nitric oxide (NO) reduces pulmonary hypertension in acute respiratory failure. Soluble nitric oxide donors (NO/nucleophile adducts-NONOates) are less cumbersome to deliver and may offer clinical advantage compared with inhaled NO. The objective of this study was to examine the pulmonary and systemic hemodynamic effects of tracheal aerosolization of a new class of NONOates in a porcine model of experimentally induced pulmonary hypertension. DESIGN: Prospective, randomized, controlled study. SETTING: Research laboratory. SUBJECTS: Yorkshire pigs (n = 18), weighing 11.4 to 16.4 kg. INTERVENTIONS: In anesthetized, mechanically ventilated, instrumented pigs, steady-state pulmonary hypertension (SSPH) was induced using a thromboxane agonist (U46619). Control animals received tracheal aerosolization of saline (n = 6); EP/NO animals received tracheal aerosolization of ethylputreanine NONOate (EP/ NO, n = 6); and DMAEP/NO animals received aerosolized 2-(dimethylamino) ethylputreanine NONOate (DMAEP/NO, n = 6). MEASUREMENTS AND MAIN RESULTS: Mean pulmonary (MPAP) and mean systemic arterial pressures (MAP), atrial pressures, cardiac output, and arterial blood gases were measured following drug instillation. DMAEP/NO animals had significant reductions in pulmonary vascular resistance index (PVRI) and MPAP at all time points compared with SSPH and control animals (p < .05), while systemic vascular resistance index did not change. EP/NO animals had a significant reduction in PVRI and MPAP at some time points compared with SSPH and control animals. For both NONOate-treated animal groups, MAP and cardiac index did not change significantly compared with SSPH and control animals (p < .05). CONCLUSIONS: In this porcine model of pulmonary hypertension, intratracheal aerosolization of soluble NO donors results in sustained reduction of pulmonary hypertension without reducing systemic arterial pressure. Intermittent aerosolization of NONOates may be an alternative to continuously inhaled NO in the treatment of acute pulmonary hypertension.

Acute Disease↗
PubMed1998

In vitro reactivation of latent equid herpesvirus-1 from CD5+/CD8+ leukocytes indirectly by IL-2 or chorionic gonadotrophin.

IL-2 and equine chorionic gonadotrophin (eCG) initiated reactivation of equid herpesvirus-1 (EHV-1) from venous lymphocytes at a frequency of 1/10(-5). Indirect immunofluorescence showed that > 80% of virus-positive leukocytes were CD5+/CD8+ with the remaining 20% being CD5+/CD8-/CD4-. Cocultivation demonstrated that the reactivated virus was infectious. In addition, virus was reactivated in vitro from leukocytes of > 70% of horses by the mitogens phytohaemagglutinin (PHA) and pokeweed mitogen (PWM). Transfer of supernatants showed that IL-2 and eCG acted indirectly by causing the release of other mediators from adherent cells; these mediators then reactivated EHV-1 from T cells. Blocking experiments with anti-IL-2 showed that PWM and PHA acted via IL-2 but that eCG did not. This is the first clear definition of the lymphoid cells that harbour latent EHV-1 in vivo and correlates with current RT-PCR and in situ hybridization of latency-associated transcripts in lymphocytes. This method of reactivation in vitro can be used to detect horses carrying latent EHV-1 in vivo and also has the potential to dissect the sequence of events involved in reactivation in vitro.

Animals↗
PubMed1998

Association of salivary immunoglobulin A antibody and initial mutans streptococcal infection.

We explored the relationship between mutans streptococcal infection and the development of salivary IgA antibody during initial colonization. Repetitive swabbing (n = 292) of the teeth of 33 children revealed that 45% became infected with mutans streptococci between 13 and 36 months of age. In contrast, mutans streptococci could not be detected in 18 children whose last sample was taken at 39-81 months of age (median age = 62 months). During the period of mutans streptococcal infectivity, immunoglobulin A (IgA) antibody to several mutans streptococcal antigens appeared in most children, whether or not infection had been demonstrated. Robust responses to mutans streptococcal components occurred during or shortly after, but not before the period of mutans streptococcal infectivity. No consistent differences were observed among the summarized patterns of response of infected and uninfected groups of children, although the IgA Western blot patterns of individual subjects were often quite distinct. For example, sets of siblings, who would be presumed to be challenged with similar maternal mutans streptococcal clonotypes, were shown to develop qualitatively different salivary IgA responses to mutans streptococcal components. These results support a discrete period for mutans streptococcal infection and may suggest that the level of maternal infection is a factor in the success of infection of the child during this period. The data also suggest that exposure to mutans streptococci is a sufficient condition for robust mucosal IgA responses to mutans streptococcal antigens during the period of infectivity and that these responses may be different, even among siblings.

Antibodies, Bacterial↗
PubMed1998

Structural integrity of infant salivary immunoglobulin A (IgA) in IgA1 protease-rich environments.

IgA1 protease-secreting Streptococcus mitis often dominate the oral flora of the neonate and young infant at a time when salivary IgA concentrations are low and usually enriched in the secretory IgA1 subclass. To study the possible influence of these degradative enzymes on emerging host immunity, the presence of IgA1 protease-secreting streptococci was related to the structural integrity of salivary IgA in 24 infants who were between 3 and 18 weeks of age. At least one IgA1 protease-secreting strain could be isolated from the oral mucosa of 79% of the infants and comprised a mean of 38% of the total streptococcal flora of these infants. Chromatographic analyses of resting whole saliva from 16 infants revealed, however, that 95% of the secretory IgA (range 88-100%) remained intact, indicating that minimal immediate IgA proteolysis occurred in the bulk salivary phase. Proteolysis of infant salivary IgA, presumably by indigenous IgA1 protease, could be observed after extended (more than 7 h) in situ incubation of whole saliva at 37 degrees C. Salivary IgA antibody activities to S. mitis components were demonstrated by Western blot in infants colonized with an IgA1 protease-secreting flora. Preliminary evidence suggested that salivary antibody activity in some infants may be directed to IgA1 protease. Thus, the infant's antibody defenses not only appear very early in life but are substantively intact in the bulk salivary phase, even when the oral cavity is colonized with IgA1 protease-secreting streptococcal flora.

Blotting, Western↗
PubMed1998

The effect of dimethylsulfoxide on the water transport response of rat hepatocytes during freezing.

Successful improvement of cryopreservation protocols for cells in suspension requires knowledge of how such cells respond to the biophysical stresses of freezing (intracellular ice formation, water transport) while in the presence of a cryoprotective agent (CPA). This work investigates the biophysical water transport response in a clinically important cell type--isolated hepatocytes--during freezing in the presence of dimethylsulfoxide (DMSO). Sprague-Dawley rat liver hepatocytes were frozen in Williams E media supplemented with 0, 1, and 2 M DMSO, at rates of 5, 10, and 50 degrees C/min. The water transport was measured by cell volumetric changes as assessed by cryomicroscopy and image analysis. Assuming that water is the only species transported under these conditions, a water transport model of the form dV/dT = f(Lpg([CPA]), ELp([CPA]), T(t)) was curve-fit to the experimental data to obtain the biophysical parameters of water transport--the reference hydraulic permeability (Lpg) and activation energy of water transport (ELp)--for each DMSO concentration. These parameters were estimated two ways: (1) by curve-fitting the model to the average volume of the pooled cell data, and (2) by curve-fitting individual cell volume data and averaging the resulting parameters. The experimental data showed that less dehydration occurs during freezing at a given rate in the presence of DMSO at temperatures between 0 and -10 degrees C. However, dehydration was able to continue at lower temperatures (< -10 degrees C) in the presence of DMSO. The values of Lpg and ELp obtained using the individual cell volume data both decreased from their non-CPA values--4.33 x 10(-13) m3/N-s (2.69 microns/min-atm) and 317 kJ/mol (75.9 kcal/mol), respectively--to 0.873 x 10(-13) m3/N-s (0.542 micron/min-atm) and 137 kJ/mol (32.8 kcal/mol), respectively, in 1 M DMSO and 0.715 x 10(-13) m3/N-s (0.444 micron/min-atm) and 107 kJ/mol (25.7 kcal/mol), respectively, in 2 M DMSO. The trends in the pooled volume values for Lpg and ELp were very similar, but the overall fit was considered worse than for the individual volume parameters. A unique way of presenting the curve-fitting results supports a clear trend of reduction of both biophysical parameters in the presence of DMSO, and no clear trend in cooling rate dependence of the biophysical parameters. In addition, these results suggest that close proximity of the experimental cell volume data to the equilibrium volume curve may significantly reduce the efficiency of the curve-fitting process.

Animals↗
PubMed1998

Structural and antigenic characteristics of Streptococcus sobrinus glucan binding proteins.

Three purified glucan binding proteins (GBP-2, GBP-3, and GBP-5) from Streptococcus sobrinus 6715 were compared structurally by mass spectroscopy of tryptic fragments and antigenically by Western blot analysis with rat antisera to each GBP or to peptides containing putative glucan binding epitopes of mutans streptococcal glucosyltransferases. Structural and antigenic analyses indicated that GBP-3 and GBP-5 are very similar but that both are essentially unrelated to GBP-2. None of these S. sobrinus GBPs appeared to have a strong antigenic relationship with GBPs from Streptococcus mutans. Thus, S. sobrinus GBP-2 and GBP-3 appear to be distinct proteins with potentially different functions. S. sobrinus GBP-5 may be a proteolytic fragment of GBP-3, or, alternatively, the genes coding for these proteins may be closely related.

Amino Acid Sequence↗
PubMed1998

Aerosolized soluble nitric oxide donor improves oxygenation and pulmonary hypertension in acute lung injury.

Acute respiratory distress syndrome (ARDS) is a major cause of morbidity and mortality in critically ill patients. The associated ventilation/perfusion mismatch and pulmonary hypertension are amenable to treatment with inhaled nitric oxide (NO) gas. Compounds formed by reacting NO with various nucleophiles (NONOates) release NO spontaneously and induce vasodilation. Intratracheally administered NONOates result in selective reduction in pulmonary hypertension. We hypothesized that a nebulized NONOate would improve oxygenation and reduce pulmonary vascular resistance in oleic acid-induced acute lung injury and pulmonary hypertension. Pigs underwent catheterization of the pulmonary artery, left atrium, and right atrium, and a flow probe was positioned around the pulmonary artery. Acute lung injury and pulmonary hypertension were induced with intravenous oleic acid. Animals were randomly assigned to receive either nebulized saline or the NONOate 2-(dimethylamino)ethylputreanine/NO (DMAEP/NO). Hemodynamic, gas exchange, pulmonary function, methemoglobin, and nitrite/nitrate measurements were obtained for 60 min. Animals in the DMAEP/NO group had improvement in PaO2 as compared with control animals (from 139 +/- 19 mm Hg to 180 +/- 19 mm Hg in the DMAEP/NO group [n = 6]; and from 144 +/- 6 mm Hg to 150 +/- 9 mm Hg in the saline group [n = 6], p < 0.05). After aerosol treatment, animals in the DMAEP/NO group had a greater reduction in pulmonary vascular resistance index (PVRI) than did control animals (from 81 +/- 17 dyne. s/cm5/kg to 34 +/- 8 dyne. s/cm5/kg; and from 104 +/- 16 dyne. s/cm5/kg to 64 +/- 11 dyne. sec/cm5/ kg in the saline group at 60 min, p < 0.05). There were no differences between the groups in systemic vascular resistance index (SVRI), cardiac index (CI), methemoglobin, nitrite/nitrate, or lung pathology scores. We conclude that DMAEP/NO improves oxygenation and has selective pulmonary vasodilating properties without causing significant systemic toxicity in this porcine model of acute lung injury.

Administration, Inhalation↗
PubMed1998

The pharmacokinetics, metabolism, and tissue residues of beta-adrenergic agonists in livestock.

Since the early 1980s the usefulness of dietary beta-agonists to improve the efficiency of feed utilization and(or) to enhance carcass leanness in livestock species has been well documented. Less well documented are the pharmacokinetic properties, biotransformation pathways, and tissue residue profiles of beta-agonists used to enhance leanness in experimentally or illegally treated animals. Pharmacokinetic data for clenbuterol, cimaterol, fenoterol, L-644,969, ractopamine, salbutamol, and terbutaline have been published but biotransformation and tissue residue studies for these compounds in livestock species are sparse. In general, beta-agonists having halogenated aromatic ring systems are metabolized by oxidative and conjugative pathways and have long plasma half-lives, whereas beta-agonists having hydroxylated aromatic rings are metabolized solely by conjugation and have relatively short plasma half-lives. Beta-Agonists having high oral bioavailabilities, long plasma half-lives, and relatively slow rates of elimination have high oral potencies in humans. Residues of such illegally used compounds in edible tissues of livestock represent a genuine risk to consumers. Conversely, beta-agonists having low oral bioavailabilities, short plasma half-lives, and rapid rates of elimination have low oral potencies in humans. Residues of such compounds in edible tissues of properly treated animals would not likely represent a credible risk to consumers of such products. The reviewed data indicate that the development of a safe and effective beta-agonist for use in livestock is possible.

Adrenergic beta-Agonists↗
PubMed1998

Total radioactive residues and clenbuterol residues in edible tissues, and the stereochemical composition of clenbuterol in livers of broilers after exposure to three levels of dietary [14C]clenbuterol HCl and three preslaughter withdrawal periods.

Thirty-six broiler chickens were randomly assigned to .5, 1.0, or 2.0 ppm dietary [14C]clenbuterol HCl for a 2-wk period starting at 5 wk of age. Four birds from each treatment were slaughtered after withdrawal periods of 0, 7, or 14 d. Total radioactive residues (TRR; clenbuterol HCl equivalents) were measured in adipose tissue, kidney, liver, skin with adhering adipose tissue, bile, blood, brain, gastrointestinal tract, heart, lung, spleen, and testes; parent clenbuterol was measured in liver and kidney. In edible tissues, TRR were roughly proportional to dietary [14C]clenbuterol level and inversely proportional to duration of the withdrawal period; kidney TRR ranged from nondetectable (14 d of withdrawal, .5 and 1.0 ppm treatments) to 211.5 ppb for the 2.0 ppm treatment at zero withdrawal. Liver TRR were detectable for all treatment and withdrawal periods. Rapid depletion of TRR from edible tissues occurred during the first 7 d of the withdrawal period, but depletion of TRR was much slower thereafter. Parent clenbuterol was below the limit of detection (1 ppb) or was undetectable in liver and kidney for all dietary levels after 7 and 14 d of withdrawal, but it represented 22 to 48% of the total radioactive residues at 0 withdrawal. The inactive S (+) stereoisomer constituted approximately 73% of the total clenbuterol residue in livers of chickens slaughtered with no withdrawal period, and the active R (-) stereoisomer accounted for the remainder. These data indicate that radioactive residues of clenbuterol were present well after parent clenbuterol had depleted from edible tissues in chickens, and the predominant stereoisomer remaining in livers at slaughter was the inactive isomer.

Adipose Tissue↗
PubMed1998

Distribution of radiocarbon after intramammary, intrauterine, or ocular treatment of lactating cows with carbon-14 nitrofurazone.

Three lactating Holstein cows (634 to 698 kg) were dosed, respectively, with 65.6 mg (44.5 microCi/mg), 131.2 mg (20.1 microCi/mg), or 8.4 mg (141.3 microCi/mg) of [14C]nitrofurazone by intramammary, intrauterine, or topical ocular administration. Intramammary and intrauterine treatments were single doses; ocular treatment was daily for 4 consecutive d (2.1 mg/d). Cows were slaughtered after 72-h withdrawal periods. Excreta and milk were quantitatively collected from each cow after dosing. Seventy-two hours after treatment, urine, feces, and milk contained 62.9, 17.6, and 2.3%, respectively, of the radiocarbon administered intramammarily to the cow. Radioactive residues in milk collected from the dosed quarter were 150 ppb (nitrofurazone equivalents) and were 39 ppb in milk collected from the undosed quarters at 12 h after dosing. Urine, feces, and milk from the cow that received the intrauterine dose contained 12.24, 5.17, and 0.13% of the administered dose, respectively, at 72 h after treatment. Concentrations of total radioactive residues in milk were 9.3 ppb at 12 h after dosing. For the cow that was dosed ocularly, the cumulative excretion of radiocarbon in urine, feces, and milk was 17.6, 28.5, and 0.5% of the dose, respectively. Milk residues from the cow that was dosed ocularly were never > 1 ppb of nitrofurazone equivalents. Livers and kidneys contained the greatest amounts of residues relative to other edible tissues. Parent nitrofurazone was not suitable as a marker compound to determine total residues in milk using HPLC analysis. Radioactive residues were available systemically and were excreted in milk after intramammary, intrauterine, or ocular application of [14C]nitrofurazone. Illegal residues in milk and edible tissues would result from the administration of nitrofurazone to lactating cows.

Animals↗
PubMed1998

Horticultural therapy: the garden benefits everyone.

Horticulture therapy (HT) is an applied adjuctive therapy, using plants and gardening materials, to help the client with mental illness to improve social skills, self-esteem, and use of leisure time. HT provides a nonthreatening context for the development of a therapeutic alliance between client and nursing student. HT provides a group experience for the student nurse, allowing the promotion of therapeutic community, assessment of patient status, and management of a therapy session from start to finish via the nursing process.

Chronic Disease↗
PubMed1998

Ectopic thyroid nodular goiter presenting as a porta hepatis mass.

An ectopic thyroid goiter was found in a 58-year-old woman who presented with abdominal and low back pain, diarrhea, and generalized weakness. Initial workup, including abdominal CT scan, revealed a mass extending from the duodenum to the porta hepatis. After resection and upon pathologic examination of the tissue, nodular arrangement of thyroid follicles and colloid lakes with focal hyperplastic and nodular goiter changes were identified.

Abdominal Pain↗
PubMed1998

Effects of short-term altitude training and tapering on left ventricular morphology in elite swimmers.

Short or long-term athletic training has been associated with left ventricular (LV) morphological adaptations, including increases in wall thickness, cavity dimension and estimated LV mass. A limitation of previous studies assessing the 'athlete heart' was that exercise training was performed at sea level. Since the 1968 Olympic summer games a popular method of maximizing athletic performance has been to use altitude training (AT) as a means of improving sea level performance. However, the effects of short term AT and taper training on LV morphology have not been well studied. Based on this limitation, the effects of three weeks of intense AT (1848 m) or low level control training (CT) (1050 m) followed by two weeks of taper training were investigated in 15 elite swimmers between 16 and 21 years of age. Short term AT or CT training followed by two weeks of taper training was not associated with alterations in LV diastolic cavity dimension (AT pre 53.3 +/- 2.8 mm versus post 52.6 +/- 4.3 mm; CT pre 52.9 +/- 3.7 mm versus post 51.2 +/- 4.0 mm), ventricular septal wall thickness (AT pre 9.6 +/- 1.0 mm versus post 9.4 +/- 1.1 mm; CT pre 8.4 +/- 1.2 mm versus post 8.6 +/- 1.1 mm), estimated LV mass (AT pre 186.4 +/- 45.8 g versus post 190.0 +/- 48.2 g; CT pre 159.1 +/- 35.8 g versus post 160.1 +/- 40.8 g) or fractional shortening (AT pre 36.8 +/- 3.5% versus post 34.8 +/- 2.7%; CT pre 32.6 +/- 5.0% versus post 32.8 +/- 4.7%). However, a main time effect, independent of training intervention, was observed for posterior wall thickness (pre 8.7 +/- 1.4 mm versus post 9.3 +/- 1.1 mm, P < 0.05). Therefore, with the exception of posterior wall thickness, short term AT followed by two weeks of taper training appears not to be associated with alterations in LV morphology or systolic function.

Adaptation, Physiological↗
PubMed1997

Deriving shape space parameters from immunological data.

We present a method for deriving shape space parameters that are consistent with immunological data, and illustrate the method by deriving shape space parameters for a model of cross-reactive memory. Cross-reactive memory responses occur when the immune system is primed by one strain of a pathogen and challenged with a related, but different, strain. Much of the nature of a cross-reactive response is determined by the quantity and distribution of the memory cells, raised to the primary antigen, that cross-react with the secondary antigen. B cells with above threshold affinity for an antigen lie in a region of shape space that we call a ball of stimulation. In a cross-reactive response, the intersection of the balls of stimulation of the primary and secondary antigens contains the cross-reactive B cells and thus determines the degree of cross-reactivity between the antigens. We derive formulas for the volume of intersection of balls of stimulation in different shape spaces and show that the parameters of shape space, such as its dimensionality, have a large impact on the number of B cells in the intersection. The application of our method for driving shape space parameters indicates that, for Hamming shape spaces, 20 to 25 dimensions, a three or four letter alphabet, and balls of stimulation of radius five or six, are choices that match the experimental data. For Euclidean shape spaces, five to eight dimensions and balls of stimulation with radius about 20% of the radius of the whole space, match the experimental data.

Antigens↗
PubMed1997

Differential regulation and function of CD73, a glycosyl-phosphatidylinositol-linked 70-kD adhesion molecule, on lymphocytes and endothelial cells.

CD73, otherwise known as ecto-5'-nucleotidase, is a glycosyl-phosphatidylinositol-linked 70-kD molecule expressed on different cell types, including vascular endothelial cells (EC) and certain subtypes of lymphocytes. There is strong evidence for lymphocyte CD73 having a role in several immunological phenomena such as lymphocyte activation, proliferation, and adhesion to endothelium, but the physiological role of CD73 in other cell types is less clear. To compare the biological characteristics of CD73 in different cell types, we have studied the structure, function, and surface modulation of CD73 on lymphocytes and EC. CD73 molecules on lymphocytes are shed from the cell surface as a consequence of triggering with an anti-CD73 mAb, mimicking ligand binding. In contrast, triggering of endothelial CD73 does not have any effect on its expression. Lymphocyte CD73 is susceptible to phosphatidylinositol phospholipase, whereas only a small portion of CD73 on EC could be removed by this enzyme. Furthermore, CD73 on EC was unable to deliver a tyrosine phosphorylation inducing signal upon mAb triggering, whereas triggering of lymphocyte CD73 can induce tyrosine phosphorylation. Despite the functional differences, CD73 molecules on lymphocytes and EC were practically identical structurally, when studied at the protein, mRNA, and cDNA level. Thus, CD73 is an interesting example of a molecule which lacks structural variants but yet has a wide diversity of biological functions. We suggest that the ligand-induced shedding of lymphocyte CD73 represents an important and novel means of controlling lymphocyte-EC interactions.

5'-Nucleotidase↗
PubMed1997

IL-1 beta convertase (ICE) does not play a requisite role in apoptosis induced in T lymphoblasts by Fas-dependent or Fas-independent CTL effector mechanisms.

Both IL-1beta convertase (ICE) and other members of the ICE-like family of proteases have been reported to play a role in Fas-mediated apoptosis. Con A-stimulated T lymphoblasts generated from splenocytes isolated from ICE-deficient H-2b mice were found to be more susceptible than wild-type lymphoblasts to DNA fragmentation induced by H-2b-specific CTL derived from normal or Fas ligand-deficient gld/gld mice. Trinitrophenyl (TNP)-modified, H-2b target cell-specific CTL were generated from perforin-deficient mice and were found to induce DNA fragmentation only in target cells expressing functional Fas receptors. Similar rates of DNA fragmentation were induced in TNP-modified ICE -/- and ICE +/+ T lymphoblast targets by perforin -/- TNP-modified, H-2b target cell-specific CTL. In addition, anti-Fas Abs induced apoptosis in thymocytes, Con A-stimulated spleen T cells, LPS-stimulated spleen B cells, and thymocytes from ICE -/- mice. However, DNA fragmentation induced by either allospecific FasL-defective CTL, or by perforin-deficient, TNP-modified, H-2b target cell-specific CTL was prevented in ICE -/- target cells loaded by electroporation with Ac-DEVD-CHO, an inhibitor of CPP32 and related ICE family proteases. These findings indicate that ICE does not play a requisite role in Fas-dependent or Fas-independent mechanisms of apoptosis induced in peripheral T lymphoblasts by CTL. However, both major pathways of CTL-induced apoptosis appear to be dependent on the enzymatic activity of other ICE family proteases.

Animals↗