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Biomedical subjects

J E Anderson

Publications and source records attributed to J E Anderson.

At least 127 records · Page 7Linked to original sources

The integrated inpatient management model. Lessons for managed care.

The Integrated Inpatient Management Model was a 2.5-year controlled prospective trial of using a clinical information system to direct and monitor physician and hospital practice on general medicine services of an 880-bed university hospital. For the over 2,000 admissions on both a control service and the intervention service, the mean length of stay (LOS) decreased when compared with historic norms (0.68 and 0.95 days respectively; P < 0.01 for both). This difference in mean LOS represents a savings of 580 hospital days for the intervention over the control service; (95% confidence interval, 300 to 1420 days). There also was a trend for the intervention service to have fewer LOS outliers than expected (P = 0.14). Ancillary service use decreased by 17% on both control and intervention services (a trend that disappeared after the study was terminated), while other internal medicine services experienced a 29% increase in this measure of resource use. The intervention service experienced fewer preventable deaths (P = 0.04), but there were no differences in global quality of care measures, readmission and mortality rates, and patient satisfaction. This use of a clinical information system is a prototype for the systems that will be needed for all forms of managed care.

Ancillary Services, Hospital↗

Pemphigus sera recognize conformationally sensitive epitopes in the amino-terminal region of desmoglein-1.

To identify regions of the Desmoglein-1 (Dsg1) extracellular domain that are targeted by pemphigus antisera, cDNA sequences encoding various regions of the Dsg1 extracellular domain were ligated to sequences encoding the E-cadherin extracellular anchor and transmembrane and cytoplasmic domains. These constructs were then expressed in mammalian cells, and pemphigus sera were tested for the ability to recognize the Dsg1 extracellular domains. When analyzed by immunoblot, very few pemphigus foliaceus sera recognized the Dsg1 domains. To determine whether pemphigus sera recognize non-denatured Dsg1 domains, constructs were expressed in cultured cells and tested for reactivity with pemphigus sera using live-cell immunofluorescence. The pemphigus foliaceus sera reacted strongly with the Dsg1 extracellular domain by live-cell immunofluorescence and recognized predominantly the amino-terminal region of the Dsg1 extracellular domain. In addition, sera from patients with pemphigus vulgaris also demonstrated strong reactivity with the Dsg1 extracellular domain when tested using live-cell immunofluorescence. In contrast, sera from normal human controls and sera from bullous pemphigoid patients did not react with the Dsg1 extracellular domain. These data indicate that both pemphigus foliaceus and pemphigus vulgaris sera react with conformationally sensitive epitopes in the amino-terminal region of Dsg1.

Base Sequence↗

Auditory and visual semantic priming using different stimulus onset asynchronies: an event-related brain potential study.

Semantic priming effects (behavioral and electrophysiological) were compared in the visual and auditory modalities across three stimulus onset asynchronies (SOAs; 0, 200, and 800 ms). When both prime and target were presented in the visual modality (the prime just to the left of a fixation point and the target to the right), there were N400 priming effects present across the three SOAs. However, the N400 in the 0-ms SOA condition extended longer in time (800 vs. 500 ms) than in the other SOAs. When both the prime and target were presented in the auditory modality (the prime to the right ear and the target to the left), the largest priming effects were found for the 800-ms SOA. Moreover, there was a relatively early priming effect present in the 0- and 800-ms SOA conditions but not in the 200-ms condition. The results are discussed in terms of modality differences in the time course of word comprehension processes.

Adolescent↗

An update on allogeneic marrow transplantation for myelodysplastic syndrome.

Ninety-three patients with myelodysplastic syndrome with either excess blasts or life-threatening cytopenia received cyclophosphamide and total body irradiation (88 patients) or busulfan (5 patients) followed by allogeneic (90 patients) or syngeneic (3 patients) marrow infusion. Thirty-eight patients are disease-free survivors between 1.8 and 11.3 years (median 6.1 years) after transplantation. The median Karnofsky performance status of the survivors is 100%, and only 2 have a performance status of < 80%. Eighteen patients relapsed and the remaining 37 died without evidence for relapse. The 5-year actuarial disease-free survival, relapse, and non-relapse mortality rates are 40%, 29%, and 44%, respectively. The actuarial relapse rate was higher among patients with excess blasts at the time of transplantation compared to those without excess blasts (49% vs. 4%, p = 0.0001), resulting in a lower disease-free survival (31% vs. 54%, p = 0.07). Increasing age was associated with a lower disease-free survival (p = 0.02). In a multivariate analysis, younger age, shorter disease duration, and absence of excess blasts were associated with improved outcome. We recommend that patients with myelodysplasia with appropriate marrow donors, especially patients less than age 40, undergo marrow transplantation early during the disease course, before the disease progresses or life-threatening complications develop.

Adolescent↗

Development of a swine animal model for the study of sudden infant death syndrome.

An animal model with selective cardiac autonomic denervation was developed in neonatal swine for the purpose of future studies concerning the possible role of abnormal cardiac innervation in the etiology of sudden infant death syndrome. Twenty-six 4- to 8-day old piglets were randomly assigned to one of the following treatment groups: right stellate ganglionectomy (RSG), left stellate ganglionectomy (LSG), right cardiac vagotomy (RCV), and sham-operated control group. Piglets were anesthetized with Saffan and mechanically ventilated on room air. The thoracic wall was opened, and the sternum was divided, permitting exposure of pleura, heart, and lungs. After completion of one of these operative procedures, the thoracic wall was closed in layers. On successful recovery from anesthesia and extubation, piglets were returned to their sows. Postoperative administration of antibiotics was performed during the first week. Electrocardiograms were recorded once a week over an 8-week period. The sham-operated control group had a postnatal increase in QTc and decrease in heart rate. The RSG group had significantly longer QTc than the sham-operated control group QTc, whereas the RCV group had significantly shorter QTc interval than sham-operated controls. Surgical complications caused the death of two piglets (hemorrhage in one and aspiration in the other), infection caused the death of one piglet 2 weeks after surgery, and three died of unknown causes (one from the RSG group and two from the RCV group). The cause of death for these three animals could not be determined (necropsy was not revealing) because they were not monitored at the time of their demise.(ABSTRACT TRUNCATED AT 250 WORDS)

Alfaxalone Alfadolone Mixture↗

Prostatic imaging: the role of transrectal ultrasound.

Until a few years ago, there was no acceptable imaging modality available for the prostate gland. Since the high frequency endo-rectal ultrasound transducers have been developed, transrectal ultrasound (TRUS) has gained wide acceptance as the method of choice for imaging assessment of common prostate conditions including prostate carcinoma.

Humans↗

Posttranslational regulation of plakoglobin expression. Influence of the desmosomal cadherins on plakoglobin metabolic stability.

Desmosomes are adhesive intercellular junctions that act as cell surface attachment sites for intermediate filaments. The desmosomal glycoproteins, desmogleins and desmocollins, are members of the cadherin family of adhesion molecules. In addition, desmoglein has been shown to coimmunoprecipitate with the junctional protein plakoglobin. To characterize further the interaction between plakoglobin and the desmosomal cadherins, stable mouse fibroblast (L-cells) cell lines were generated that express plakoglobin, desmoglein and plakoglobin, or desmocollin and plakoglobin. L-cell lines transfected with a plasmid encoding human plakoglobin expressed plakoglobin mRNA but very little plakoglobin protein. However, plakoglobin protein was expressed at high levels in L-cells coexpressing either desmoglein or desmocollin. In addition, both desmocollin and desmoglein were found to coimmunoprecipitate with plakoglobin. The transient expression of desmoglein in L-cell lines expressing plakoglobin mRNA resulted in the formation of a complex between plakoglobin and desmoglein and in the accumulation of plakoglobin protein. Furthermore, the rate of plakoglobin protein degradation was decreased by 15-20-fold in cell lines expressing either desmoglein or desmocollin. These results demonstrate that the desmosomal cadherins posttranslationally regulate plakoglobin expression by decreasing the rate of plakoglobin degradation.

Animals↗

Structure of PvuII endonuclease with cognate DNA.

We have determined the structure of PvuII endonuclease complexed with cognate DNA by X-ray crystallography. The DNA substrate is bound with a single homodimeric protein, each subunit of which reveals three structural regions. The catalytic region strongly resembles structures of other restriction endonucleases, even though these regions have dissimilar primary sequences. Comparison of the active site with those of EcoRV and EcoRI endonucleases reveals a conserved triplet sequence close to the reactive phosphodiester group and a conserved acidic pair that may represent the ligands for the catalytic cofactor Mg2+. The DNA duplex is not significantly bent and maintains a B-DNA-like conformation. The subunit interface region of the homodimeric protein consists of a pseudo-three-helix bundle. Direct contacts between the protein and the base pairs of the PvuII recognition site occur exclusively in the major groove through two antiparallel beta strands from the sequence recognition region of the protein. Water-mediated contacts are made in the minor grooves to central bases of the site. If restriction enzymes do share a common ancestor, as has been proposed, their catalytic regions have been very strongly conserved, while their subunit interfaces and DNA sequence recognition regions have undergone remarkable structural variation.

Amino Acid Sequence↗

The effects of hyperthyroidism on muscular dystrophy in the mdx mouse: greater dystrophy in cardiac and soleus muscle.

Muscle damage and repair were studied in mdx mice treated with triiodothyronine (T3) for 14 days. Hindlimb and cardiac muscles were examined for the severity of dystrophy, the degree of muscle centronucleation, and fiber size. In control and mdx mice, cardiac hypertrophy and skeletal muscle atrophy were present after T3 treatment. Both cardiac and soleus (but not fast-twitch) muscles had larger, more frequent dystrophic lesions in T3-treated mdx mice, and mdx soleus had an increased area of new myotubes after T3. Skeletal myogenesis in mdx mice may have been delayed by excess T3, possibly related to the general reduction in staining for basic fibroblast growth factor in hyperthyroid mice. These are the first observations of a metabolic perturbation which worsens mdx dystrophy and possibly repair in a muscle-specific manner, and are likely related to T3-induced changes in myosin heavy chain expression, and to increased mechanical strain on dystrophin-deficient muscles.

Animals↗

The effects of altered metabolism (hypothyroidism) on muscle repair in the mdx dystrophic mouse.

After dystrophic damage, the limb muscles of the mdx mouse recover very effectively compared to muscles in Duchenne muscular dystrophy (DMD) patients. Since thyroid hormone is required for muscle development and integrity, we examined whether a deficiency of the hormone, induced by 0.05% propylthiouracil (PTU) in drinking water over 8 weeks, would be deleterious to the myogenesis and muscle repair in control and mdx mice. Measured metabolic and growth parameters confirmed hypothyroidism in PTU-treated mice. Histological and morphometric techniques were used to study myogenesis and the repair of the tibialis anterior muscle (TA) after crush injury in mdx mice and their nondystrophic controls (C57B1/10ScSn). After 8 weeks, PTU-treated TA from mdx mice had larger crush sites and lower myotube density than TA in untreated mdx mice. In unoperated mdx TA, there was a larger proportionate area of active dystrophy and smaller fiber diameter in PUT-treated than in untreated mdx TA, which suggested that PTU increased the activity of dystrophy as well. In contrast, in control TA neither the regeneration of myotubes or fiber diameter were affected significantly by PTU. Therefore, these results suggest that mdx muscle regeneration is more affected by hypothyroidism than normal muscle repair. This may be due to the larger pool of muscle precursors in mdx than control muscle, and a possible impairment of precursor cell proliferation or fusion during myotube formation.

Aging↗

Expression, purification, and crystallization of restriction endonuclease PvuII with DNA containing its recognition site.

We have overexpressed the type II restriction endonuclease PvuII (R-PvuII) in E. coli, prepared large amounts of the homogeneous enzyme, and crystallized it with an oligonucleotide carrying a PvuII recognition site. The cocrystals are orthorhombic space group P2(1)2(1)2(1) with cell constants a = 95.8 A, b = 86.3 A, c = 48.5 A, and diffract X-rays to at least 2.7 A. There is a complex of two protein subunits and one oligonucleotide duplex in the asymmetric unit.

Base Sequence↗

Anabolic steroid treatment increases myofiber damage in mdx mouse muscular dystrophy.

In order to study whether myofiber size is an important determinant of the severity of dystrophic injury, mdx and control mice were treated with an anabolic steroid, nandrolone decanoate, for 3 weeks. Treatment resulted in a population of significantly smaller fibers in both strains, and was accompanied by an increase in the proportionate area or the number of foci of dystrophic injury in mdx soleus (slow-twitch) or tibialis anterior plus extensor digitorum longus (fast-twitch) muscles, respectively. As well, serum creatine kinase activity was increased in steroid-treated mdx mice. Fiber centronucleation, an index of accumulated injury and repair, in steroid-treated mdx soleus was doubled compared to that observed in soleus muscles from untreated mdx mice. There was no change in the distribution of immunoreactive basic fibroblast growth factor, important in muscle cell proliferation, with the increased damage from treatment. However, presumptive muscle precursor cells (identified by immunoperoxidase histochemistry for neural cell adhesion molecule), appeared to be more abundant in foci of very recent fiber damage in muscles from steroid-treated than untreated mdx mice. Results show that mdx dystrophy is worsened by anabolic steroid treatment, possibly by altered influences on muscle use patterns and muscle precursor fusion, and is not accompanied by an increase in fiber size.

Animals↗

The pituitary-muscle axis in mdx dystrophic mice.

As myogenesis, muscle growth and differentiation and growth factor expression are influenced by thyroid and growth hormone (GH) levels, it is important to investigate the possibility that altered activity of the pituitary-muscle axis prevents the lethal progression of mdx dystrophy and/or contributes to the muscle fiber hypertrophy of limb muscles. The ultrastructure of pituitary and thyroid tissues in age-matched control and mdx mice at 2 and 12 months of age was examined. Pituitary GH, and serum thyroid stimulating hormone (TSH), thyroid hormone (T4), and creatine kinase (CK) levels were measured. Mdx thyroid gland structure was similar to age-matched control glands. Mdx thyroid gland weighed significantly more than in age-matched controls, but was unchanged relative to body weight. TSH and T4 levels were not different from levels in control mice. High CK levels reflected the active dystrophy in mdx muscles. Somatotrophs in mdx pituitaries were hypertrophied in comparison to controls, indicating increased secretory activity, and pituitary GH was slightly but significantly greater in old mdx female mice compared to age-matched female controls. These observations rule out hypopituitary or hypothyroid function as a reason for the low impact of dystrophin deficiency in mdx muscles. Results suggest a contribution by raised GH to the fiber hypertrophy in mdx limb and heart muscle, which might also assist the large capacity for limb muscle regeneration in mdx mice.

Aging↗

Validation of a food-repertory grid with a diabetic population.

The application of a psychology tool, the repertory grid, was explored. A diabetic sample was used to evaluate this new assessment tool. The grid measures attitudes about food and was created by determining elements (food items) and constructs (adjectival phrases) as identified by diabetic participants and dietitians. The grid was administered twice to 17 diabetic participants to determine applicability. The interindividual correlation coefficients ranged from 0.24 to 0.54 for elements and from 0.24 to 0.61 for constructs. The most stable components can be used for a grid designed to help dietitians with counseling. Clients would fill out a grid so that problem areas in the way of attitudes about food could be pinpointed. Because many diabetic persons fail to comply with their diets, a new and innovative tool is needed. The possibilities for grid development are abundant among other clinical populations for whom dietary management is important.

Attitude↗

What should be next for nutrition education?

Nutrition education is a process by which we assist people in making decisions regarding their eating practices by applying knowledge from nutrition science about the relationship between diet and health. Multiple factors affect food choice, all of which must be assessed if effective educational approaches and nutrition messages are to be developed for all segments of the population. Research enhances practice; however practice must inform research and guide its direction. There is still a need to improve our understanding of the food decision-making process, as well as the processes in and influences on changing eating behavior. Research will need to be directed into many areas in the next decade and beyond. For example, the commonalities and differences between the different ethnic groups, income levels and literacy levels in the population demand attention. Innovative techniques for reaching diverse population groups and rural areas will need to be created. Nutrition education in the future will undoubtedly involve greater collaboration both within the USDA as well as between the USDA and other agencies. Research efforts will be enhanced as will the practice of nutrition education by greater collaborations, partnerships, and linkages.

Health Education↗

Evaluation of a Bayesian approach to the pharmacokinetic interpretation of cyclosporin concentrations in renal allograft recipients.

The utility of a Bayesian parameter estimation program in the interpretation of cyclosporin concentrations was investigated in a group of 32 patients following renal transplantation. The program was evaluated by comparing concentrations predicted from individual estimates of pharmacokinetic parameters with measured concentrations. A one-compartment model incorporating an exponential, time-related change in clearance was used for data collected in the first 4 weeks after transplantation, and predictions of concentrations measured during weeks 5-14 were made using three schemes: a changing clearance model using all data from week 1 onward; a changing clearance model using data from week 4 onward; and a nonchanging clearance model using data from week 4 onward. Results demonstrated that predictions made by the Bayesian program were unreliable during the first 4 weeks of therapy, but that there was a progressive improvement as time after transplantation increased. The changing clearance model was superior to the constant clearance model and its performance was not compromised by including data from the first 4 weeks of therapy. Although the Bayesian approach may help with the interpretation of blood cyclosporin concentrations during maintenance therapy, the large variability in the pharmacokinetics of orally administered cyclosporin limits the usefulness of the approach in the early weeks following transplantation.

Adult↗

Gonococcal transferrin-binding protein 2 facilitates but is not essential for transferrin utilization.

Pathogenic Neisseria species have been shown to scavenge iron from transferrin (Tf), although the mechanism is not yet fully understood. Two iron-repressible proteins that exhibit Tf-binding activity have been identified. This work describes the cloning and sequencing of tbpB, a 2.1-kb gene in N. gonorrhoeae that encodes Tbp2, an 85-kDa iron-repressible lipoprotein. Transcriptional interruption of tbpB had a strong polar effect on tbpA, the structural gene for Tbp1 that is located immediately downstream from tbpB. Such tbpB mutants did not express either Tbp2 or Tbp1, did not bind Tf to whole cells, did not grow on Tf plates, and did not take up iron from Tf. A mutant in which most of tbpB was deleted, presumably leaving tbpA under transcriptional control of the tbpB promoter, was constructed. This mutant did not express Tbp2 but expressed wild-type levels of Tbp1 and possessed the phenotype of reduced binding of Tf, decreased iron uptake from Tf, but normal growth on Tf plates. Mutants expressing Tbp2 and not Tbp1 bound less Tf, did not grow on Tf plates, and did not take up iron from Tf. These results suggest that tbpB and tbpA are polycistronic. Tbp2 apparently facilitates binding of Tf but is not essential for acquisition of iron from Tf under these in vitro conditions.

Amino Acid Sequence↗