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Biomedical subjects

E Swanson

Publications and source records attributed to E Swanson.

At least 19 recordsLinked to original sources
PubMed1997

Overexpression of the rat sarcoplasmic reticulum Ca2+ ATPase gene in the heart of transgenic mice accelerates calcium transients and cardiac relaxation.

The Ca2+ ATPase of the sarcoplasmic reticulum (SERCA2) plays a dominant role in lowering cytoplasmic calcium levels during cardiac relaxation and reduction of its activity has been linked to delayed diastolic relaxation in hypothyroid and failing hearts. To determine the contractile alterations resulting from increased SERCA2 expression, we generated transgenic mice overexpressing a rat SERCA2 transgene. Characterization of a heterozygous transgenic mouse line (CJ5) showed that the amount of SERCA2 mRNA and protein increased 2. 6-fold and 1.2-fold, respectively, relative to control mice. Determination of the relative synthesis rate of SERCA2 protein showed an 82% increase. The mRNA levels of some of the other genes involved in calcium handling, such as the ryanodine receptor and calsequestrin, remained unchanged, but the mRNA levels of phospholamban and Na+/Ca2+ exchanger increased 1.4-fold and 1.8-fold, respectively. The increase in phospholamban or Na+/Ca2+ exchanger mRNAs did not, however, result in changes in protein levels. Functional analysis of calcium handling and contractile parameters in isolated cardiac myocytes indicated that the intracellular calcium decline (t1/2) and myocyte relengthening (t1/2) were accelerated by 23 and 22%, respectively. In addition, the rate of myocyte shortening was also significantly faster. In isolated papillary muscle from SERCA2 transgenic mice, the time to half maximum postrest potentiation was significantly shorter than in negative littermates. Furthermore, cardiac function measured in vivo, demonstrated significantly accelerated contraction and relaxation in SERCA2 transgenic mice that were further augmented in both groups with isoproterenol administration. Similar results were obtained for the contractile performance of myocytes isolated from a separate line (CJ2) of homozygous SERCA2 transgenic mice. Our findings suggest, for the first time, that increased SERCA2 expression is feasible in vivo and results in enhanced calcium transients, myocardial contractility, and relaxation that may have further therapeutic implications.

Animals↗
PubMed1997

Motoric responses to sucrose in postmature and term infants.

Postmature infants calm less when presented with sucrose solutions than term infants. To further assess the influence of postmaturity on sucrose responsivity, several motoric responses were examined in healthy term neonates and chronically stressed postmature (> or = 288 days gestational age (GA) e.g., > 41 weeks) neonates with Clifford's Syndrome tested between 5-91 h of age. Following baseline observations, each subject was presented with 0.1 ml of a 14% sucrose solution for 10 s each min for 5 min, and observations were continued for 5 min following stimulation. During sucrose stimulation and poststimulation phases, postmature infants showed more tremors during quiet state than term infants. Across conditions, postmature infants exhibited increased finger sucking, rhythmic sucking, but less mouth opening and arm movements than healthy, term infants. Sequence analysis revealed that short-latency mouthing, repetitive movements of the upper and lower lips, followed sucrose infusion reliably in postmature infants, but not term infants. These results suggest that postmaturity is associated with: 1. Increased oral behaviors associated with arousal and self soothing; and 2. Increased sucrose reactivity, as indicated by contingent mouthing and increased tremors.

Arousal↗
PubMed1995

Managing constipation using a research-based protocol.

Constipation, a common health problem particularly for elderly and hospitalized patients, can cause abdominal pain, discomfort, gas, headaches, nausea, anorexia, a bad taste in the mouth, and potentially adds to functional loss and length of stay. As part of a quality improvement initiative, a research-based interdisciplinary protocol was developed to prevent constipation in hospitalized immobile vascular surgery patients. Using a combination of dietary fiber, increased fluid, and hygiene measures over a 3-year period, incidence of constipation was reduced from 59% to about 9%. The incidence of impaction was eliminated and requests for laxatives and enemas were reduced from 59% to about 8%.

Clinical Nursing Research↗
PubMed1994

Alzheimer's special care units.

An overview of Alzheimer's special care units is provided, including the several models that have been used to guide their development. Philosophy and programming, physical and social environments, staff selection and training, admission and discharge criteria, family programming, and quality and cost features are described. Evaluation and research of special units and interventions for residents with Alzheimer's, their family members and staff caregivers are discussed.

Alzheimer Disease↗
PubMed1991

Clinical comparison of ocular irrigation fluids following chemical injury.

This study tested the hypothesis that four ocular irrigating solutions were equally irritating during copious irrigation. We conducted a prospective, double-blind study of patients with chemical exposure to the eye. Each underwent cross-over irrigation with all of the following in random order: normal saline (NS), lactated Ringer's (LR), normal saline adjusted to pH 7.4 with sodium bicarbonate (NS + Bicarb), and Balanced Saline Solution Plus (BSS Plus, Alcon Laboratories, Fort Worth, TX). Compared with traditional NS and LR, NS + Bicarb tended to be more comfortable. BSS Plus was statistically superior (P less than .05) to NS and preferred over LR and NS + Bicarb. Three patients demanded discontinuance of NS or NS + Bicarb infusions. All solutions had comparable normalization of conjunctival pH and degree of injection. Alternate solutions including BSS Plus should be considered for use in those patients whose poor tolerance to normal saline threatens to delay or interrupt eye irrigation following a chemical injury.

Bicarbonates↗
PubMed1990

Radial artery infections and aneurysms after catheterization.

Twelve patients in whom radial artery infections developed after catheterization in an intensive care unit over a 2-year period were reviewed. The incidence of local infection was 0.4%. An increased risk of infection was associated with prolonged catheterization (greater than 4 days). Aneurysms developed in five patients. Signs of septic emboli were present in two patients, including Osler's nodes, Janeway's lesions, and fingertip infarcts. In 6 of the 12 patients, the radial artery infection resolved with antibiotic treatment alone. The five patients with infected aneurysms were treated successfully with antibiotics and surgical excision. The radial artery was reconstructed by use of a vein graft in one patient. We believe that patients not responding promptly to antibiotics or patients with infected aneurysms are best treated by surgical excision.

Adolescent↗
PubMed1990

The radial forearm flap: reconstructive applications and donor-site defects in 35 consecutive patients.

Thirty-five consecutive patients treated with the radial forearm flap were reviewed. This flap was used in head and neck reconstruction in 25 patients, soft-tissue cover of an extremity in 9 patients, and as a new technique for penile reconstruction in 1 patient. Osteocutaneous flaps were used for mandibular reconstruction in 13 patients. In 6 patients innervated flaps were used to provide sensation on the dorsum of the hand or on the weight-bearing surface of the foot. There was only one total flap failure and no partial failures. Recipient-site complications were few, with prompt healing and very acceptable appearance. Donor-site complications included partial loss of the skin graft with tendon exposure in 10 patients (33 percent), an unsatisfactory appearance in 5 patients (17 percent), and one case of radial fracture (8 percent). On functional testing, there was no significant loss of strength or joint mobility in the donor extremity in 19/20 patients. The authors recommend measures to reduce donor-site morbidity and conclude that, with an acceptable donor site, this flap is valuable in a variety of reconstructive applications.

Adult↗
PubMed1990

The radial forearm flap: a biomechanical study of the osteotomized radius.

An experimental study was undertaken to determine the effect of an osteotomy on radial strength and to compare two techniques used clinically to perform these osteotomies. Forty preserved human cadaveric radii were randomized into osteotomized (20) and nonosteotomized (20) groups. Osteotomized bones were further randomized into beveled-corner (10) and squared-corner (10) groups. A 9-cm-long, one-third thickness segment of bone was removed, similar to the defect resulting from a radial osteocutaneous transfer. All bones were tested to breaking using a four-point bending apparatus. Osteotomized radii were significantly weakened, with breaking strengths only 24 percent of the control group. Although the beveled osteotomy group appeared stronger than the squared osteotomy group, this finding was not significant with the numbers tested. In view of the weakness of the osteotomized radius, we recommend excising no more than one-third of the radial diameter and postoperative immobilization of the forearm for 8 weeks. A beveled osteotomy prevents overcutting at the corners and allows better visualization of the depth of cut. With these measures, the incidence of fracture may be reduced.

Biomechanical Phenomena↗
PubMed1988

MPTP and MPTP analogs induced cell death in cultured rat hepatocytes involving the formation of pyridinium metabolites.

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) which has been shown to produce a Parkinson-like syndrome in humans and monkeys also causes cell death in cultures of rat hepatocytes. Treatment of cells with MPTP or its metabolite MPP+ (1-methyl-4-phenyl pyridinium ion), resulted in leakage of lactic acid dehydrogenase and 14C-labeled adenine nucleotides, as well as marked depletion of ATP and glutathione. Deprenyl, a specific inhibitor of monoamine oxidase-B, the enzyme catalyzing the oxidation of MPTP into MPP+, blocked the lethal effect of MPTP, but gave no protection from MPP+-induced cell death. The 4'-fluoro and 4'-chloro analogs of MPTP evoked toxicities similar to that of the parent compound, while N-butyl-PTP, 4'-amino-MPTP, and 2'-methyl-MPTP were relatively less toxic. N-Acetylamino-MPTP was found virtually nontoxic. The cell death produced by these analogs was also associated with leakage of [14C]adenine nucleotides, which is an indicator of loss of ATP from cells. All these compounds except the N-acetylamino analog were converted to corresponding pyridinium metabolites by liver cells when analyzed by high-pressure liquid chromatography and plasma desorption mass spectrometry. MPTP and its analogs also served as substrates for rat liver mitochondrial monoamine oxidase to varying degrees. Toxicity of various analogs, with the noticeable exception of 2'-methyl-MPTP, was inhibited by deprenyl. These findings indicate that the conversion of MPTP and its analogs to corresponding pyridinium metabolites is essential for the expression of toxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Construction, purification and biological activities of recombinant human interleukin-2 analogs.

Fourteen human interleukin-2 (IL-2) analogs have been cloned and expressed in E. coli, starting from a chemically synthesized gene for human IL-2 optimized for expression in E. coli. These analogs were purified to greater than 95% purity as determined by SDS-PAGE, and were measured for biological activity in a 3H-thymidine incorporation assay using an IL-2 dependent murine T-cell line (CTLL). One analog was made which eliminated the N-terminal 23 amino acids from the protein by replacing one restriction endonuclease fragment with another. This analog, which begins at an internal methionine, had no detectable CTLL activity. Thirteen analogs were constructed using oligonucleotide site-directed mutagenesis. Four of these analogs were truncated at various residues near the C-terminus (residues 106, 116, 121 and 126). These analogs had at least 500-fold lower CTLL activities than the natural recombinant IL-2. The remaining nine analogs had substitutions at 1, 2, or all 3 of the three cysteine residues in the protein (residues 58, 105 and 125). Substituting an alanine, asparagine, aspartic acid, or serine at residue 125 resulted in highly active molecules with CTLL activities similar to that of the natural recombinant IL-2. The analogs with alanine and serine substitutions at residue 125 actually had slightly higher CTLL activities than the natural recombinant IL-2. Substituting alanine for cysteine at position 125 and serine for cysteine at either position 58 or 105 yielded analogs with about 150-fold lower CTLL activities than natural recombinant IL-2. Substituting an alanine for the cysteine at position 125 and serines for cysteines at both positions 58 and 105 resulted in an analog with 30-fold lower CTLL activity than the natural recombinant IL-2. The ten analogs with less than 1.0% of the CTLL activity of natural recombinant IL-2 were tested for competition with the natural recombinant IL-2 by mixing a 10-to 100- fold excess of the analog with the natural recombinant IL-2 and assaying the mixture in the CTLL assay. None of these analog mixtures resulted in a lower activity than mixing the natural recombinant IL-2 with buffer alone, implying that none of these analogs effectively competes with the natural recombinant IL-2 for binding to IL-2 receptors during incubation with the CTLL cells. If reduced binding does occur, it may be the direct cause of their lower activities.

Amino Acid Sequence↗
PubMed1985

Transcriptional regulation of a periodically controlled flagellar gene operon in Caulobacter crescentus.

Temporal regulation of flagellar gene expression in Caulobacter crescentus has been examined by a detailed analysis of the flbG-flaJ-flbH-flaK hook operon. The approximate location of the promoter for this 4.4 X 10(3) base-pair transcriptional unit was determined by deletion mapping, and the flaK gene was shown by nucleotide sequencing to code for the hook protein. flaK messenger RNA was quantified by S1 nuclease mapping with an internal restriction fragment of the gene as the 5'-labeled DNA probe. The results of these assays provide the first direct evidence that periodic expression of a flagellar gene in the C. crescentus cell cycle is regulated at the transcriptional level. The effect of altering the time of gene duplication in the cell cycle was examined by subcloning the complete hook operon on a plasmid that replicates throughout the S phase. The normal periodicity of flaK transcription and translation was maintained in this merodiploid strain, which suggests that replication alone is not sufficient to initiate flagellar gene expression. We also show that the three adjacent transcriptional units III, IV and V are required in trans for transcription of the book operon, and we discuss the possible role of these genes in the hierarchical regulation of the flagellar gene expression.

Bacterial Proteins↗
PubMed1984

Physical mapping and complementation analysis of transposon Tn5 mutations in Caulobacter crescentus: organization of transcriptional units in the hook gene cluster.

Using the cloned DNA from the hook protein gene region of Caulobacter crescentus ( Ohta et al., Proc. Natl. Acad. Sci. U.S.A. 79:4863-4867, 1982), we have identified and physically mapped 19 Tn5-induced and 2 spontaneous insertion mutations to this region of the chromosome. These nonmotile mutants define a major cluster of fla genes that covers approximately 17 kilobases on the chromosome (hook gene cluster). Complementation analysis of the mutants using DNA fragments from the region subcloned in the broad host range plasmid pRK290 has shown that these fla genes are organized into at least five transcriptional units (I to V). Transcriptional unit II contains at least one gene in addition to the hook protein gene, which makes this the first operon described in C. crescentus. Expression of the hook protein gene and the genetically unlinked flagellin A and B genes by this set of mutants also furnishes additional insights into the hierarchial regulation of flagellar genes. We have found that the spontaneous insertion mutant ( SC511 ) of the hook protein gene ( flaK ) makes no flagellin A or B and that genes downstream from the hook protein gene are required in trans for expression of the hook protein operon and the flagellin A and B genes. Recombination and complementation results thus place flaK , flaJ , flaN , and flaO (R. C. Johnson and B. Ely , J. Bacteriol . 137:627-634, 1979) in the hook gene cluster, identify at least three new genes ( flbD , flbG , and flbF ), and suggest that this cluster may contain several additional, as yet unidentified, fla genes.

Bacterial Proteins↗
PubMed1983

Aspirin usage and perioperative blood loss in patients undergoing unexpected operations.

The effect of aspirin on perioperative blood loss was studied in 52 patients undergoing unplanned operation. Twenty-two of 52 patients were found to have taken aspirin prior to operation. Five others were suspected of having taken aspirin or some aspirin-like drug prior to operation. All patients who remembered taking aspirin preoperatively had significantly decreased platelet thromboxane B2 levels caused by aspirin inhibition of platelet arachidonic acid metabolism. Eight of 22 patients who took aspirin had abnormal template bleeding times. No significant increase occurred in the perioperative blood loss of patients who had taken aspirin. Neither the aspirin induced decrease in thromboxane B2 levels nor the increase in template bleeding times was associated with an increased perioperative blood loss. We concluded that aspirin is commonly used prior to unplanned operations but that preoperative aspirin usage does not result in increased perioperative blood loss in patients with normal platelet counts and with normal coagulation factors. These results suggest that there is no need to delay operation in this group of patients because of recent aspirin ingestion.

Arachidonic Acids↗
PubMed1978

The evolution of histones.

The amino acid sequences of bovine histones H2A, H2B, H3, and H4 and the first 107 residues of rabbit thymus histone H1 were examined using newly developed procedures designed to detect and evaluate weak similarities (de Haën et al., 1976). Using the McLachlan scoring system, regions of statistically significant similarity were found between several pairs of the four smallest histones. The probability that this set of similarities could result simply from chance was estimated to be less than 10(-5). No similarity was found between the H1 sequence and the other histones. The results are interpreted to indicate that at least the C-terminal portions of the core histones evolved from a common ancestral protein.

Amino Acid Sequence↗