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Biomedical subjects

W L Smith

Publications and source records attributed to W L Smith.

At least 199 records · Page 11Linked to original sources
PubMed1991

Large postnatally acquired porencephalic cysts: unexpected developmental outcomes.

To determine the neurodevelopmental outcome for infants with posthemorrhagic intraparenchymal cysts, we reviewed retrospectively clinical, ultrasonographic, and developmental features in 16 affected children. At a mean follow-up age of 33 months, five subjects had normal cognitive outcomes (developmental quotient [DQ] or IQ greater than 83), nine had borderline to mild deficits (DQ or IQ, 52 to 83), but only three had moderate to severe deficits (DQ or IQ less than 52). Spastic cerebral palsy was present in 13 (81%); only one child (6%) had a chronic seizure disorder requiring medication. Cognitively normal children were less likely to have had neonatal seizures (P less than .05) and tended to have more localized cysts. Otherwise, we found no relationship between outcome and neonatal clinical or laboratory findings. Overall, these results suggest that although motor deficits are common in infants with severe intraventricular hemorrhage and porencephalic cysts, cognitive outcomes may be more favorable than has been suspected previously.

Brain Damage, Chronic↗
PubMed1991

Activation of a peptidergic synapse locally modulates postsynaptic calcium influx.

We examined the synaptic connection between Phe-Met-Arg-Phe-NH2 (FMRFamide)-immunoreactive neurone VD4 and its target neurone P1, both found in the central nervous system of the pond snail Helisoma trivolvis. The major FMRFamide-like peak in neurone VD4 appears to be FMRFamide itself, based on its high performance liquid chromatography (HPLC) elution time and immunoreactivity before and after oxidation, but small peaks are also present at the elution times of Phe-Leu-Arg-Phe-NH2 (FLRFamide) and Gly-Asp-Pro-Phe-Leu-Arg-Phe-NH2 (GDPFLRFamide). The modulatory actions of the neuropeptides found in neurone VD4 were tested on the postsynaptic target cell P1. Bath application of both the tetrapeptides FMRFamide and FLRFamide at a concentration of 10(-5) mol l-1 reduced the macroscopic voltage-sensitive calcium current of neurone P1 in culture; FMRFamide by 45% and FLRFamide by 51%. Bath application of the heptapeptide GDPFLRFamide (10(-5) mol l-1) reduced the calcium current by only 8%. We reconstructed the synaptic connection between VD4 and P1 in culture. Action-potential-evoked calcium transients in neurites growing from P1 cells in culture were monitored using Fura-2. Addition of FMRFamide, FLRFamide or GDPFLRFamide reduced the magnitude of the calcium transient in P1. Stimulation of VD4 mimicked the effects of peptide application and caused localized reductions in the action-potential-evoked calcium transients in P1 at the points of contact between the neurites of neurones VD4 and P1. These results suggest that neurone VD4 modulates the calcium influx of neurone P1 through the release of endogenous FMRFamide-related peptides and that this modulatory action is restricted to sites of synaptic interaction.

Animals↗
PubMed1991

Analysis of the cost-effectiveness of PACS.

Picture archiving and communications systems (PACS) have emerged as an important part of digital imaging technology. However, the future of PACS is uncertain because its economic viability is in doubt. Cost-effectiveness analysis is an accepted technique for evaluating the economics of new technologies. This paper addresses the cost-effectiveness of PACS and identifies factors that are important in determining the cost of PACS relative to film-based radiology. These include the impact of PACS on physician productivity, maintenance costs, discount rates, and the time period for amortization of capital goods. The effectiveness of PACS is also explored in terms of improvements in diagnostic accuracy and timely diagnosis. Financial and clinical impacts should be integrated to provide information about how PACS expenditures will affect radiology departments, hospitals, and national research and development objectives.

Cost-Benefit Analysis↗
PubMed1991

Radiographic manifestations of anomalies of the brain.

Congenital brain anomalies are classified as developmental anomalies, effects of teratogens, errors of histogenesis, or sequelae of infections. The imaging options for delineation of these anomalies are many; a basic understanding of the disorder is central to the effective choice of imaging modality. This review begins with a brief overview of embryogenesis then reviews the common congenital brain anomalies encountered in infants.

Brain↗
PubMed1990

Tyrosine 385 of prostaglandin endoperoxide synthase is required for cyclooxygenase catalysis.

There are spectral and biochemical data suggesting that a tyrosine group(s) is involved in the cyclooxygenase reaction catalyzed by prostaglandin endoperoxide (PGH) synthase. Treatment with tetranitromethane, a reagent which nitrates tyrosine residues, abolishes cyclooxygenase activity, but this inactivation can be largely prevented by competitive cyclooxygenase inhibitors such as ibuprofen and indomethacin. To identify sites of nitration, native PGH synthase and indomethacin-pretreated PGH synthase were incubated with tetranitromethane, and the sequences of peptides containing nitrotyrosine were determined. Three unique tyrosines (Tyr-355, Tyr-385, and Tyr-417) were nitrated in the native enzyme but not in the indomethacin-treated PGH synthase. Using site-directed mutagenesis of sheep PGH synthase, each of these tyrosines, as well as two other tyrosine residues selected as controls (Tyr-254 and Tyr-262), were replaced with phenylalanine; cos-1 cells were transfected with constructs containing cDNAs coding for the native PGH synthase and each of the five phenylalanine mutants, and microsomes from these cells were assayed for cyclooxygenase and hydroperoxidase activities. The Phe-385 mutant of PGH synthase lacked cyclooxygenase activity but retained peroxidase activity; all other mutants expressed both enzyme activities. Our results establish that Tyr-385 is essential for the cyclooxygenase activity of PGH synthase and that nitration of this residue can be prevented by indomethacin. We conclude that Tyr-385 is at or near the cyclooxygenase active site of PGH synthase and could be the tyrosine residue proposed to be involved in the first step of the cyclooxygenase reaction, abstraction of the 13-proS hydrogen from arachidonate.

Animals↗
PubMed1990

A prostaglandin E receptor coupled to a pertussis toxin-sensitive guanine nucleotide regulatory protein in rabbit cortical collecting tubule cells.

At different concentrations, prostaglandin E2 (PGE2) can either stimulate or inhibit cAMP formation in freshly isolated rabbit cortical collecting tubule (RCCT) cells, but in cultured RCCT cells PGE2 can only stimulate cAMP synthesis (Sonnenburg, W. K., and Smith W. L. (1989) J. Biol. Chem. 263, 6155-6160). Here, we report characteristics of [3H]PGE2 binding to membrane receptor preparations from both freshly isolated and cultured RCCT cells. [3H]PGE2 binding to membranes from freshly isolated RCCT cells was saturable and partially reversible. Equilibrium binding analyses indicated that in the absence of guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) there is a single class of PGE2 binding sites (KD = 4.2 +/- 0.4 nM; Bmax = 583 +/- 28 fmol/mg); in the presence of 100 microM GTP gamma S, there is also only one class of binding sites but with a somewhat lower KD = 1.2 +/- 0.5 nM (Bmax = 370 +/- 40 fmol/mg). This stimulatory effect of GTP gamma S was blocked by pretreatment of the freshly isolated RCCT cells with pertussis toxin. The relative affinities of prostanoids for the [3H]PGE2-binding site were determined to be 17,18,19,20-tetranor-16-phenoxy-PGE2-methylsulfonylamide (sulprostone) approximately PGE2 approximately PGE1 approximately 16,16-dimethyl-PGE2 greater than carbacyclin approximately PGF2 alpha greater than PGD2. This is the order of potency with which prostaglandins inhibit arginine vasopressin-induced cAMP formation in fresh RCCT cells. Interestingly, [3H]PGE2 binding to membranes from cultured cells, which, unlike fresh cells, fail to show an inhibitory response to PGE2, was only 10-20% of that observed with membranes from fresh cells; moreover, binding of [3H]PGE2 to membranes from cultured cells was neither stimulated by GTP gamma S nor inhibited by sulprostone. The prostanoid binding specificities and the unusual pertussis toxin-sensitive, stimulatory effect of GTP gamma S on binding of [3H]PGE2 to membranes from freshly isolated RCCT cells are characteristics shared by a Gi-linked PGE receptor from renal medulla (Watanabe, T., Umegaki, K., and Smith, W. L. (1986) J. Biol. Chem. 261, 14340-14349). Our results suggest that the [3H]PGE2 binding site of freshly isolated RCCT cells is the PGE receptor which is coupled to a Gi to attenuate arginine vasopressin-induced cAMP synthesis in the renal collecting tubule.

Animals↗
PubMed1990

The aspirin and heme-binding sites of ovine and murine prostaglandin endoperoxide synthases.

Acetylation of Ser-530 of sheep prostaglandin endoperoxide (PGG/H) synthase by aspirin causes irreversible inactivation of the cyclooxygenase activity of the enzyme. To determine the catalytic function of the hydroxyl group of Ser-530, we used site-directed mutagenesis to replace Ser-530 with an alanine. Cos-1 cells transfected with expression vectors containing the native (Ser-530) or mutant (Ala-530) cDNAs for sheep PGG/H synthase expressed comparable cyclooxygenase and hydroperoxidase activities. Km values for arachidonate (8 microM) and ID50 values for reversible inhibition by the cyclooxygenase inhibitors, flurbiprofen (5 microM), flufenamate (20 microM), and aspirin (20 mM), were also the same for both native and mutant PGG/H synthases; however, only the native enzyme was irreversibly inactivated by aspirin. Thus, the "active site" Ser-530 of PGG/H synthase is not essential for catalysis or substrate binding. Apparently, acetylation of native PGG/H synthase by aspirin introduces a bulky sidechain at position 530 which interferes with arachidonate binding. In related studies, a cDNA for mouse PGG/H synthase was cloned and sequenced. A sequence of 35 residues with Ser-530 at the midpoint was identical in the two proteins. Thus, Ser-530 does lie in a highly conserved region, probably involved in cyclooxygenase catalysis. Sequence comparisons of mouse and sheep PGG/H synthase also provided information about the heme-binding site of the enzyme. The sheep HYPR sequence (residues 274-277), which had been proposed to form a portion of the distal heme-binding site, is not conserved in the mouse PGG/H synthase, suggesting that this region is not the distal heme-binding site. One sequence, TIWLREHNRV (residues 303-312 of the sheep enzyme), is very closely related to the sequence TLW(L)LREHNRL common to thyroid peroxidase and myeloperoxidase. The histidine in this latter sequence is the putative axial heme ligand of these peroxidases. We suggest that the histidine (His-309) of sheep PGG/H synthase sequence is the axial heme ligand of this enzyme.

Amino Acid Sequence↗
PubMed1990

In vitro antimicrobial activity of defensins against ocular pathogens.

New approaches to antimicrobial therapy for ocular pathogens must overcome organisms that are resistant to current therapeutic modalities. This investigation examined the antimicrobial activity of novel antimicrobial neutrophil peptides (defensins NP-1 and NP-5) against isolates from clinical ocular microbial infections in humans and horses. The test panel of human clinical isolates included Candida albicans, an alpha-hemolytic Streptococcus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Morganella morganii. The test panel of equine pathogens included three clinical isolates of P aeruginosa and two clinical isolates of Staphylococcus aureus. The equine isolates were chosen for their relative resistance to commonly employed antimicrobial therapy. The two defensins differed markedly in their bactericidal activity. Defensin NP-5, at a 50-micrograms/mL concentration, exhibited minimal bactericidal activity against the majority of isolates of the test panel. The inferior microbicidal activity of NP-5 is consistent with previously published results. However, at this concentration, NP-5 did exhibit appreciable bacteriostatic activity against human ocular pathogens M morganii (74%), alpha-hemolytic Streptococcus (57%), and P aeruginosa (93%) during the 2-hour incubation period. In contrast, defensin NP-1 at 10 micrograms/mL exerted potent microbicidal activity against all isolates, effecting a 2 to 3 log10 decrease in colony-forming units within a 60-minute incubation period. Under the assay conditions employed, these findings demonstrate: (1) two distinct mechanisms by which defensins exert their antimicrobial activity against microbial pathogens associated with clinical ocular disease in humans and horses, and (2) that rabbit defensin NP-1 is a potent antimicrobial agent against a wide array of ocular pathogens.

Animals↗
PubMed1990

Long term sequelae of frostbite.

Frostbite injury in the hands and feet of a child can have long-term sequelae, Premature fusion and abnormal growth can occur in the epiphyseal cartilage.

Bone Development↗
PubMed1990

Nomenclature.

Explore the source record for details and available documents.

Arachidonic Acids↗
PubMed1990

Aortosternopexy for tracheomalacia following repair of esophageal atresia: evaluation by cine-CT and technical refinement.

During the period of 1 year (1988 to 1989), five infants, aged 3 weeks to 10 months, presented with recurrent respiratory distress following repair of esophageal atresia with tracheoesphageal fistula (EA/TEF). These patients had associated congenital anomalies, including right aortic arch (1), biliary atresia (1), and a long gap that required esophageal elongation by spiral myotomy (1). The patients were evaluated for tracheomalacia using cinecomputed tomography (cine-CT; C-100 Scanner, Imatron, San Francisco, CA), which provides images of eight levels (8-mm interval) simultaneously with 0.7 second time intervals of cine-CT. Dynamic studies of the trachea by cine-CT showed tracheal collapse that was most significant during expiration in the segment immediately above and at the aortic arch. These patients underwent aortosternopexy. Via a right second intercostal approach, the ascending aorta and aortic arch were lifted anteriorly using two to four sutures of 5-0 Tevdek on pledgets placed between the tunica media and adventitia of the side walls of the aorta and the adjacent sternum. Respiratory distress was significantly improved postoperatively. Preliminary experience with these patients allows us to conclude that (1) cine-CT is a useful technique for diagnosing tracheomalacia; (2) it provides objective indication for its correction by aortosternopexy; and (3) the refined technique in placing sutures on the aorta may reduce the surgical risks of aortosternopexy.

Anastomosis, Surgical↗
PubMed1990

Gross anatomy instruction with diagnostic images.

A new module of instruction for diagnostic imaging with emphasis on cross-sectional anatomy was developed within the existing course of gross anatomy for freshmen medical students. Two lectures introduced radiation protection, radiology history, and the basic principles of computed tomography, magnetic resonance imaging, ultrasound, and radiograph image production. Six radiographic anatomy correlation sessions allowed student-teacher interaction while studying viewbox images in a "hands on" fashion. Relevant exhibits complemented cadaver dissection. Testing established that significant improvement occurred in the students' ability to identify anatomic structures on diagnostic images.

Anatomy↗
PubMed1990

A prospective study of cognitive and noncognitive selection criteria as predictors of resident performance.

The primary purpose of this study was to compare objective measures of diagnostic radiology resident applicant performance, such as National Board (NBME) scores, with nonobjective measures, such as conscientiousness and interpersonal skills, in their prediction of resident performance. A second purpose of the study was to examine the predictive usefulness of the Accomplishment Interview (AI), a behavioral selection interview. Thirty resident applicants were interviewed using standard interviews, the AI, and objective data on the applicants were gathered. Four years later, during their diagnostic radiology residency, evaluations were gathered on these applicants, allowing for comparison of current resident performance with past predictive data. Results indicated that noncognitive factors were as important as cognitive factors in the prediction of resident behavior. Further, objective measures, such as NBME scores, failed to adequately predict residents' performance. The implications of these findings for resident selection are discussed.

Cognition↗
PubMed1990

Hemogram changes in lactating dairy cows given human recombinant granulocyte colony stimulating factor (r-MethuG-CSF).

As a prelude to mammary gland challenge experiments, this investigation was implemented to assess the hematologic changes in lactating dairy cattle induced by two dosage regimes of human recombinant colony stimulating factor (Hr-GCSF). This study documents the capability of the human recombinant colony stimulating factor to produce hematologic changes in both a time and dose dependent manner when administered to the adult lactating bovine. A screening dose of 1 microgram/kg of Hr-GCSF administered to three study subjects produced a three- to four-fold increase in peripheral blood mature neutrophil counts (P less than 0.043) by day 12 of the trial. The priming dose treatment group of four lactating cows (3 micrograms/kg of Hr-GCSF) exhibited a three- to five-fold increase in peripheral blood mature neutrophil counts (P less than 0.05) and two- to three-fold increases in white blood cell counts by day 5 of the trial. Hematologic examinations of the control group (n = 4; no Hr-GCSF administration) did not detect significant changes in their neutrophil counts over baseline values. The milk somatic cell counts did not statistically shift over baseline values in any of the control or Hr-GCSF treatment groups. When attempting to alter the course of infectious disease processes, potential applications of colony stimulating factors provide interesting speculations about new therapeutic modalities.

Animals↗
PubMed1990

Ultrafast CT of laryngeal and tracheobronchial obstruction in symptomatic postoperative infants with esophageal atresia and tracheoesophageal fistula.

We evaluated the role of ultrafast CT in the diagnosis and follow-up of nine consecutive, symptomatic infants with suspected laryngeal and tracheobronchial obstruction after surgery for esophageal atresia. With 80% or more area collapse as a criterion for the diagnosis of laryngomalacia and 50% or more for tracheomalacia, six patients had tracheomalacia, one had laryngomalacia, and two had both. Tracheomalacia was focal in four patients and diffuse, involving the thoracic trachea, in the other four. Associated bronchomalacia was present in two patients. The site and degree of abnormality were verified by endoscopy in five of nine patients. The degree of tracheal collapse did not always correlate with the size of the esophageal pouch or with the site of the tracheo-esophageal fistula. These findings support the concept that the larynx and/or tracheal walls are often abnormal in symptomatic infants with esophageal atresia, tracheoesophageal fistula, and airway obstruction. Ultrafast CT was a reliable technique for detecting and assessing the site, extent, severity, and dynamics of airway collapse in five of seven symptomatic infants with congenital tracheoesophageal anomalies when the imaging findings were compared with endoscopic findings and previously published normal standards.

Airway Obstruction↗