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Biomedical subjects

M E Johnson

Publications and source records attributed to M E Johnson.

At least 19 recordsLinked to original sources
PubMed2001

Positive selection of a gene family during the emergence of humans and African apes.

Gene duplication followed by adaptive evolution is one of the primary forces for the emergence of new gene function. Here we describe the recent proliferation, transposition and selection of a 20-kilobase (kb) duplicated segment throughout 15 Mb of the short arm of human chromosome 16. The dispersal of this segment was accompanied by considerable variation in chromosomal-map location and copy number among hominoid species. In humans, we identified a gene family (morpheus) within the duplicated segment. Comparison of putative protein-encoding exons revealed the most extreme case of positive selection among hominoids. The major episode of enhanced amino-acid replacement occurred after the separation of human and great-ape lineages from the orangutan. Positive selection continued to alter amino-acid composition after the divergence of human and chimpanzee lineages. The rapidity and bias for amino-acid-altering nucleotide changes suggest adaptive evolution of the morpheus gene family during the emergence of humans and African apes. Moreover, some genes emerge and evolve very rapidly, generating copies that bear little similarity to their ancestral precursors. Consequently, a small fraction of human genes may not possess discernible orthologues within the genomes of model organisms.

Animals↗
PubMed2001

Qualitative and quantitative analysis of proteins and peptides in milk products by capillary electrophoresis.

Milk protein is an important component of the human diet throughout much of the world. The ability to assess the relative composition and integrity of milk proteins or peptides in dairy foods or food ingredients is important because these molecules have a profound effect on product functionality and quality. This communication describes two capillary electrophoretic methods that are useful for the analysis of proteins and casein-derived peptides in cheese and milk products. One technique, which uses a buffer containing citrate/phosphate (pH 3.3), 4 M urea, and a polymeric additive in a coated capillary, is useful for qualitative and quantitative analysis of proteins and peptides in milk, cheese, and whey products. The second method employs a citrate/phosphate buffer (pH 2.8) and a bare silica capillary, and is well suited for the analysis of small, casein-derived peptides in aqueous cheese extracts.

Animals↗
PubMed2001

Strategies for improved antigen delivery into dendritic cells.

Efficacious vaccines against cancers and infectious diseases will, in general, need to elicit comprehensive immune responses, including cytotoxic T lymphocyte activity. Because of their unique T cell stimulatory capacities, dendritic cells (DC) have emerged as the most potent antigen-presenting cell. Vaccination strategies should therefore aim at the acquisition and display of the antigen(s) of choice by DC. Results from vaccination studies, in animal models and in humans, stress the need for optimized antigen delivery systems to DC, to increase vaccination efficacy as well as to improve control on the immunological outcome. Here, we discuss the advantages and limitations of several recently described methodologies for antigen delivery into DC.

Animals↗
PubMed2001

Lateral stability during forward-induced stepping for dynamic balance recovery in young and older adults.

BACKGROUND: Balance dysfunction related to lateral instability has been associated with falls and fall-related injuries among older individuals. Protective stepping for dynamic balance recovery requires the effective control of lateral body motion. This study investigated the relationship between aging, falls, and lateral stability during forward-induced stepping for dynamic balance recovery. METHODS: Forward steps were induced by a motor-driven waist-pull system in 12 younger adults, 20 healthy community-dwelling older adult nonfallers, and 18 older adults who had reported falls. Group differences in kinetic and kinematic stepping characteristics for a range of postural disturbance magnitudes were evaluated. RESULTS: Despite group similarities in anticipatory postural adjustments for minimizing lateral instability, the older fallers demonstrated significantly greater sideways body motion toward the stepping side at first-step foot contact and a more laterally directed foot placement. During the first step, forward-stepping characteristics were generally comparable between the groups, but the older fallers had an earlier liftoff time and longer step duration. CONCLUSIONS: During forward-induced protective stepping, otherwise healthy older adults who had experienced falls showed particular differences in their control of lateral body motion that were not attributable to changes in anticipatory postural mechanisms. Aging changes in controlling lateral body motion during protective stepping appear to involve factors that intervene between the first-step liftoff and foot contact and/or adaptations in stepping patterns related to prior planning.

Accidental Falls↗
PubMed2001

Plasma tranexamic acid concentrations during cardiopulmonary bypass.

UNLABELLED: Although tranexamic acid is used to reduce bleeding after cardiac surgery, there is large variation in the recommended dose, and few studies of plasma concentrations of the drug during cardiopulmonary bypass (CPB) have been performed. The plasma tranexamic acid concentration reported to inhibit fibrinolysis in vitro is 10 microg/mL. Twenty-one patients received an initial dose of 10 mg/kg given over 20 min followed by an infusion of 1 mg. kg(-1). h(-1) via a central venous catheter. Two patients were removed from the study secondary to protocol violation. Perioperative plasma tranexamic acid concentrations were measured with high-performance liquid chromatography. Plasma tranexamic acid concentrations (microg/mL; mean +/- SD [95% confidence interval]) were 37.4 +/- 16.9 (45.5, 29.3) after bolus, 27.6 +/- 7.9 (31.4, 23.8) after 5 min on CPB, 31.4 +/- 12.1 (37.2, 25.6) after 30 min on CPB, 29.2 +/- 9.0 (34.6, 23.8) after 60 min on CPB, 25.6 +/- 18.6 (35.1, 16.1) at discontinuation of tranexamic acid infusion, and 17.7 +/- 13.1 (24.1, 11.1) 1 h after discontinuation of tranexamic acid infusion. Four patients with renal insufficiency had increased concentrations of tranexamic acid at discontinuation of the drug. Repeated-measures analysis revealed a significant main effect of abnormal creatinine concentration (P = 0.02) and time (P < 0.001) on plasma tranexamic acid concentration and a significant time x creatinine concentration interaction (P < 0.001). IMPLICATIONS: A 10 mg/kg initial dose of tranexamic acid followed by an infusion of 1 mg.kg(-1).h(-1)produced plasma concentrations throughout the cardiopulmonary bypass period sufficient to inhibit fibrinolysis in vitro. The dosing of tranexamic acid may require adjustment for renal insufficiency.

Adult↗
PubMed2001

Fluvoxamine treatment of mixed anxiety and depression: evidence for serotonergically mediated anxiolysis.

Although increasing evidence suggests that selective serotonin reuptake inhibitor (SSRI) treatment may be effective for anxiety in addition to depression, SSRI anxiolysis has not been definitively related to the inhibition of serotonin (5-HT) transport. The gene that encodes for the human serotonin transporter (5-HTT) expresses its protein in neurons and in blood platelets, and both tissues respond to transport inhibition similarly in response to SSRI treatment. This study examined the relationship between the change in the 5-HTT's apparent affinity for 5-HT and the anxiolytic response in a group of 18 fluvoxamine-treated patients meeting Structured Clinical Interview for DSM-IV criteria for both generalized anxiety disorder and major depression. Significant decreases were found in both Hamilton anxiety and Hamilton depression scores over a 2-month treatment period. Robust increases were found in the apparent affinity constant (Km) for platelet 5-HT transport with treatment, and the increases covaried significantly with the decrease in anxiety (F = 4.97, p < 0.03). The pretreatment 5-HTT Km significantly correlated with the improvement in depression scores (r = 0.53, p < 0.03), consistent with the Hypothesis of Initial Conditions. These results suggest that the therapeutic effect of SSRI treatment can be linked to the magnitude and time-course of 5-HT transport inhibition effected with fluvoxamine, a drug that seems to have an antianxiety effect of the same magnitude as its effect on depression.

Adolescent↗
PubMed2001

Effect of rennet coagulation time on composition, yield, and quality of reduced-fat cheddar cheese.

This study compared the effect of coagulum firmness at cutting on composition of 50% reduced-fat Cheddar cheese. Coagulum firmness was determined by subjective evaluation by the cheese maker. Three firmness levels were tested, and these corresponded to average times of coagulant addition to cutting the curd of 25, 48, and 65 min. A slow acid-producing culture was used, and ripening times were altered to give similar curd pH values throughout cheese making. A longer rennet coagulation time (firmer coagulum at cutting) resulted in an increase in cheese moisture as well as an increase in cheese yield. The percentages of fat recovered in the cheese decreased with increasing curd firmness. The percentage of nitrogen recovered in the cheese was similar among the treatments. The amount of whey collected from the curd after milling increased as the coagulum firmness at cutting increased. Higher moisture content and lower pH of cheese made from the firmer curd at cutting contributed to softer, smoother-bodied cheeses, but the Cheddar flavor intensity was not affected.

Cheese↗
PubMed2001

Biofilm formation and contamination of cheese by nonstarter lactic acid bacteria in the dairy environment.

Defects in cheese, such as undesirable flavors, gas formation, or white surface haze from calcium lactate crystals, can result from growth of nonstarter lactic acid bacteria (NSLAB). The potential for biofilm formation by NSLAB during cheese manufacturing, the effect of cleaning and sanitizing on the biofilm, and bacterial growth and formation of defects during ripening of the contaminated cheese were studied. Stirred-curd Cheddar cheese was made in the presence of stainless steel chips containing biofilms of either of two strains of erythromycin-resistant NSLAB (Lactobacillus curvatus strain JBL2126 or Lactobacillus fermentum strain AWL4001). During ripening, the cheese was assayed for total lactic acid bacteria, numbers of NSLAB, and percentage of lactic acid isomers. Biofilms of L. curvatus formed during cheese making survived the cleaning process and persisted in a subsequent batch of cheese. The starter culture also survived the cleaning process. Additionally, L. curvatus biofilms present in the vat dislodged, grew to high numbers, and caused a calcium lactate white haze defect in cheese during ripening. On the other hand, biofilms of L. fermentum sloughed off during cheese making but could not compete with other NSLAB present in cheese during ripening. Pulsed-field gel electrophoresis results verified the presence of the two biofilm strains during cheese making and in the ripening cheese. Probable contamination sites in the plant for other NSLAB isolated in the cheese were identified, thus supporting the hypothesis that resident NSLAB biofilms are a viable source of contamination in the dairy environment.

Biofilms↗
PubMed2001

Elderly patients' reports of physical restraint experiences in intensive care units.

BACKGROUND: Use of physical restraints has undesirable sequelae. As they weigh the risks and benefits of protocols for reducing the use of restraints, staff members in intensive care units, where restraints are most used in hospitals, need to know how well elderly patients remember being restrained and how patients perceive the use of restraints. OBJECTIVES: To estimate the proportion of patients who remember being restrained, describe the experience from the patients' perspectives, and describe any distress caused by use of restraints within the overall experience of being in the intensive care unit. METHODS: Transcripts of semistructured, audiotaped interviews of patients who had been in the medical or surgical intensive care unit in any of 3 eastern and midwestern medical centers were analyzed by question and for overall themes. RESULTS: Six patients (40%) remembered some aspect of being restrained but did not report great distress. Patients accepted restraints as needed because of the lack of alternatives. Patients reported remembering that they should not perform certain behaviors but being unable to stop themselves. Patients cited hallucinations and intubation as major stressors in the intensive care unit. Patients' continuing health problems after discharge from the intensive care unit severely limited recruitment of subjects. CONCLUSIONS: Patients do not remember great distress specifically related to the use of restraints, but the overall situation leading to use of restraints is disturbing if remembered. The discovery of methods to reduce the distress of intubation and hallucinations could decrease use of restraints.

Aged↗
PubMed2001

Studies of the erythrocyte spectrin tetramerization region.

Human erythrocyte spectrin dimers associate at the N-terminal region of alpha spectrin (alpha N) and the C-terminal region of beta-spectrin (beta C) to form tetramers. We have prepared model peptides to study the tetramerization region. Based on phasing information obtained from enzyme digests, we prepared spectrin fragments consisting of the first 156 amino-acid residues and the first 368 amino-acid residues of alpha-spectrin (Sp alpha 1-156 and Sp alpha 1-368, respectively), and found that both peptides associate with a beta-spectrin model peptide, with an affinity similar to that found in alpha beta dimer tetramerization. Spin label EPR studies show that the region consisting of residues 21-46 in alpha-spectrin is helical even in the absence of its beta-partner. Multi-dimensional nuclear magnetic resonance studies of samples with and without a spin label attached to residue 154 show that Sp alpha 1-156 consists of four helices, with the first helix unassociated with the remaining three helices, which bundle to form a triple helical coiled coil bundle. A comparison of the structures of erythrocyte spectrin with other published structures of Drosophila and chicken brain spectrin is discussed. Circular dichroism studies show that the lone helix in Sp alpha-156 associates with helices in the beta peptide to form a coiled coil bundle. Based on NMR and CD results, we suggest that the helices in Sp alpha 1-156 exhibit a looser (frayed) conformation, and that the helices convert to a tighter conformation upon association with its beta-partner. This suggestion does not rule out possible conversion of a non-structured conformation to a structured conformation in various parts of the molecule upon association. Spectrin mutations at residues 28 and 45 of alpha-spectrin have been found in patients with hereditary elliptocytosis. NMR studies were also carried out on Sp alpha 1-156R28S, Sp alpha 1-156R45S and Sp alpha 1-156R45T. A comparison of the structures of Sp alpha 1-156 and Sp alpha 1-156R28S, Sp alpha 1-156R45S and Sp alpha 1-156R45T is discussed.

Amino Acid Sequence↗
PubMed2000

NMR analysis of secondary structure and dynamics of a recombinant peptide from the N-terminal region of human erythroid alpha-spectrin.

We have studied the nuclear magnetic resonance solution secondary structure of the N-terminal region in human erythroid alpha-spectrin using a recombinant model peptide of alpha-spectrin consisting of residues 1-156. Pulsed field gradient diffusion coefficient measurements show that the model peptide exists as a monomer under the solution conditions used. The first 20 residues are in a random coil conformation, followed by a helix of 25 residues and then a random coil segment before the next helix. The random coil nature of this linker was confirmed by the presence of fast internal motion from (15)N relaxation measurements. The second, third and fourth helices are thought to form the triple helical bundle structural domain, consistent with previous studies. Our study shows that the N-terminal region of alpha-spectrin prior to the first structural domain forms a well behaved helix without its beta-spectrin partner.

Amino Acid Sequence↗
PubMed2000

Overexpression of cathepsin B and urokinase plasminogen activator is associated with increased risk of recurrence and metastasis in patients with chondrosarcoma.

BACKGROUND: Deregulation of the cellular protease network has been shown to be responsible for aggressive clinical behavior in several common human malignancies. In the current study, the authors evaluated the expression patterns of proteases in patients with chondrosarcoma of bone and correlated these patterns with clinical outcome. METHODS: The expression levels of urokinase plasminogen activator; matrix metalloproteinase types-1, -2, and -9; and cathepsins B and L were determined immunohistochemically in 114 cases of chondrosarcomas of bone and were correlated with their clinicopathologic parameters as well as with long term follow-up data. RESULTS: Overexpression of cathepsin B was associated with a high rate of local recurrence (P = 0.006) and a decreased recurrence free survival (P = 0.005). Overexpression of urokinase plasminogen activator was associated with an increased rate of metastasis (P = 0. 013), a decreased metastasis free survival (P = 0.016), and a decreased 5-year overall survival rate (P = 0.048). The univariate Cox model showed that tumor extension into soft tissue, high histologic grade, and overexpression of cathepsin B were predictors of adverse outcome. Multivariate analysis showed only overexpression of cathepsin B and tumor extension into soft tissue to be independent predictors of local recurrence. CONCLUSIONS: Overexpression of cathepsin B and urokinase plasminogen activator can be used to identify those patients with chondrosarcoma of bone who have an increased risk of local recurrence and distant metastases.

Adult↗
PubMed2000

Nonaqueous capillary electrophoresis of fatty acids derivatized with a near-infrared fluorophore.

Saturated linear fatty acids, derivatized with a near-infrared absorbing fluorescent dye, were separated in 100% methanol with 12.5 mM tetraethylammonium chloride added as a charge carrier. Separation at 380 V/cm was acceptable for acids that differed in length by a single carbon. The labeled linear fatty acids behaved as random coils in the nonaqueous separation medium, as shown in a fit to a simple theoretical expression. However, even in 100% methanol with a trimethylsilylated capillary, significant adsorption to the capillary wall occurred, which reduced resolution and slowed the separation. Addition of water to the methanol medium caused significant differences in separation behavior of high molecular weight acids (>C16). Addition of a cetyltrimethylammonium bromide surfactant to the separation medium dynamically coated the capillary and greatly improved the separation. The surfactant also interacted with the acyl tail, apparently causing it to collapse. Resolution in an optimal separation medium (20 mM surfactant) ranged from 1.6 to 1.1, depending on chain length, and theoretical plate heights were under 4 microm (N > 10(5)). Resolution was more than adequate to separate stearic (C18:0) from oleic (C18:1) acid, as well as other unsaturated C18 homologues.

Electrophoresis, Capillary↗
PubMed2000

Ion trap mass spectrometry of trimethylsilylamides following gas chromatography.

Fatty acid amides are a class of compounds with newly discovered biological activity. The ion trap mass spectrometric characteristics of silylated fatty acid amides were examined. Silylation of primary fatty acid amides is required prior to gas chromatography owing to thermal instability of the underivatized compound. The trimethylsilylated amides do not yield a molecular ion under normal electron ionization conditions (70 eV). With methane as a chemical ionization gas, the [M+H]+ ion appears. The [M+H]+ ion also appears when the helium buffer gas pressure is increased in the ion trap. There are three fragments other than the [M+H]+ peak that are predominant in the ion trap mass spectra of these compounds. Two of the fragments have been reported previously, namely the m/z 59 and the [M-71]+ fragments. The fragment of m/z 72 was identified and is the result of a rearrangement. Isotopic labeling was used to confirm fragment identity and the composition of the rearrangement products. Fragmentation patterns were affected by the amide chain length and concentration.

Amides↗
PubMed2000

Telephone survey of Alaskan pharmacists' nonprescription needle-selling practices.

OBJECTIVES: To determine the availability of nonprescription needles and syringes (NS) through pharmacy sales and to assess the impact of pharmacy policies and municipal paraphernalia laws on pharmacists' selling practices. DESIGN: Telephone survey of all pharmacies in Alaska's four largest cities. SETTING: Anchorage, Fairbanks, Juneau, and Ketchikan, Alaska. SUBJECTS: A single pharmacist from each pharmacy represented in the cities' phone books. MAIN OUTCOME MEASURES: Reports of (1) pharmacies' policies and individual pharmacists' procedures regarding the nonprescription sale of NS, (2) pharmacists' selling practices, and (3) identification of conditions that may affect pharmacists' decisions to sell nonprescription NS. RESULTS: Response rate of 86% (37/43); 77% of pharmacists reported selling at least one nonprescription NS in the last month. Store policy was related to selling practices; however, there was no difference in selling practices between a city with a paraphernalia law and cities without such laws. Logistic regression revealed pharmacists were more likely to sell NS if they worked in chain pharmacies and estimated that a high number of other local pharmacists sell nonprescription NS. CONCLUSION: NS are available through nonprescription sales in Alaskan pharmacies. The majority of pharmacies have store policies that permit pharmacists to sell nonprescription NS, either in all cases or at their discretion. Municipal paraphernalia laws do not determine the selling practices of individual pharmacists.

Alaska↗
PubMed2000

Preoperative embolization of bone metastases from renal cell carcinoma.

The purpose of this study was to correlate the effectiveness of preoperative embolization with the blood loss and transfusion requirement during surgery for bone metastases from renal cell carcinoma. Twenty-eight preoperative embolizations in 26 patients with renal cell carcinoma metastatic to bone were retrospectively evaluated and divided into two groups: Group A included the embolizations that resulted in complete devascularization of the lesion as defined by the post-embolization arteriograms, and group B included those with an incomplete result. The two groups were compared with regard to blood loss and transfusion requirement during surgery, by unpaired two-tailed Student's t-test. Where complete embolization was effected (group A, 10 cases), there was a mean blood loss of 535 +/- 390 ml. When a less than complete embolization was achieved (group B, 18 cases), the mean blood loss was 1.247 +/- 1.047 ml (p = 0.049). The red blood cell transfusion in group A was 1.3 +/- 1 units, whereas in group B it was 2.4 +/- 1.2 (p = 0.03). Preoperative embolization of bone metastases from renal cell carcinoma with subsequent complete devascularization leads to significant reduction of blood loss during surgery. Interventional radiologists should pursue and embolize every feeder to the metastasis, because any less than complete devascularization increases the amount of blood loss and the amount of red blood cell transfusion during surgery.

Aged↗
PubMed2000

Evaluation of root reinforcement of endodontically treated teeth.

OBJECTIVES: The purpose of this study was to test the root reinforcing capabilities of a glass ionomer sealer and to test whether pretreatment of the instrumented canal to alter or remove the smear layer might enhance the reinforcement. STUDY DESIGN: Ninety single-canaled roots of standardized dimensions were instrumented to International Standards Organization size 45 and were analyzed for resistance to vertical fracture. Six groups were tested (n = 15). RESULTS: No significant difference in fracture resistance was observed between any of the groups. CONCLUSIONS: Under the conditions of this study, reinforcement of endodontically treated mature teeth by placement of adhesive materials in the root was not demonstrated.

Analysis of Variance↗