Biomedical subjects

A Nelson

Publications and source records attributed to A Nelson.

At least 19 recordsLinked to original sources

PubMed1996

Electrochemical modeling of electron and proton transfer to ubiquinone-10 in a self-assembled phospholipid monolayer.

Ubiquinone-10 (UQ) was incorporated at concentrations ranging from 0.5 to 2 mol% in a self-assembled monolayer of dioleoylphosphatidylcholine (DOPC) deposited on a mercury drop electrode, and its electroreduction to ubiquinol (UQH2) was investigated in phosphate and borate buffers over the pH range from 7 to 9.5 by a computerized chronocoulometric technique. The dependence of the applied potential for a constant value of the faradaic charge due to UQ reduction upon the electrolysis time t at constant pH and upon pH at constant t was examined on the basis of a general kinetion approach. This permitted us to conclude that the reduction of UQ to UQH2 in DOPC monolayers takes place via the reversible uptake of one electron with the formation of the semiubiquinone radical anion UQ.-, followed by the rate-determining protonation of this anion with UQH. formation; this neutral radical is more easily reduced than UQ, yielding the ubiquinol UQH2. In spite of the very low concentration of hydrogen ions as compared with that of the acidic component of the buffer, the only effective proton donor is the proton itself; this strongly suggests that the protonation step takes place inside the polar head region of the DOPC monolayer, which is only accessible to protons.

Biophysical Phenomena↗

PubMed1996

Patient evaluation of prone carts used in spinal cord injury.

Prone carts are used for mobility by individuals with spinal cord injury who cannot use a wheelchair due to the risk of aggravating existing pressure ulcers. A prone cart is a flat/horizontal cart with a fixed height, propelled by the user while laying in a prone position. Patients reported that prolonged use of a prone cart resulted in chronic neck, shoulder and back pain. Additionally the existing prone carts lack user accessible angle adjustability, chest support area, as well as a storage, eating or working area. An interdisciplinary research team collaborated to address these concerns. Three prone carts were evaluated: E&J, Gendron, and a newly developed prototype, MIAD/PVA. Questionnaires were administered to caregivers and patients regarding usage and effectiveness of the prone carts as well as the features of an ideal cart. This data led to the design and refinement of a prototype prone cart which was tested on 20 patients and 19 caregivers at the SCI Centers of the Milwaukee and Tampa VAMC's from 1994-1995. The new prone cart enables the user to lie at an angle rather than laying flat. This position has been found to relieve back and neck pressure. With an hydraulic system, the the user can adjust both the front and rear angles of the cart to achieve desired comfort. In addition, a front deck provides an eating and working area. This study resulted in research-based information and criteria for the design of new prone carts. Findings of this pilot study will be incorporated in a development merit review proposal to the VA Rehabilitation Research & Development service for the design of a new manual and motorized prone cart. The researchers are collaborating with Ortho-Kinetics Inc. to promote ease in manufacturing.

Activities of Daily Living↗

PubMed1995

An in-gel assay for protein tyrosine phosphatase activity: detection of widespread distribution in cells and tissues.

A method is described for the detection of protein tyrosine phosphatase activity in sodium dodecyl sulfate-polyacrylamide gels. A radiolabeled substrate, 32P-labeled poly(glutamic acid-tyrosine) (random copolymer) is incorporated into gels prior to polymerization. Following electrophoresis, the sodium dodecyl sulfate is removed; the proteins are fully denatured by soaking gels in 6 M guanidine hydrochloride and then renatured by incubation in buffers containing 0.04% Tween 40 and high concentrations of reducing agents. Protein tyrosine phosphatase activity is detected in autoradiographs of dried gels as regions from which the 32P has been selectively removed. Electrophoresis of known cytoplasmic protein tyrosine phosphatases indicates activity as the predicted molecular weights. As little as 10 pg of some cytoplasmic phosphatases is detectable. However, transmembrane tyrosine phosphatases, such as CD45, are detected only at very high protein loadings in this assay. Electrophoresis of whole cell lysates indicates multiple bands of tyrosine phosphatase activity, some of which comigrate with known cytoplasmic protein tyrosine phosphatases. The activity is inhibited by sodium orthovanadate or the omission of reducing agents during the renaturation process. The assay has been used to analyze embryonic and adult tissues, as well as whole cell lysates. A similar profile of bands of tyrosine phosphatase activity is seen with many different cells and tissues. However, some that are highly differentiated, such as adult skeletal muscle, erythrocytes, or sperm, reveal either a reduced level of tyrosine phosphatase activity or a simplified profile of bands.

Adult↗

PubMed1995

Cloning of the murine counterpart of the tumor-associated antigen H-L6: epitope mapping of the human and murine L6 antigens.

The murine monoclonal antibody (mAb) L6 was raised against human lung carcinoma cells and found to recognize an antigen which is highly expressed on lung, breast, colon, and ovarian carcinomas. Promising results in phase 1 clinical studies with this antibody or its chimerized counterpart suggest the antigen recognized by mAb L6 (H-L6) is an attractive target for monoclonal antibody-based cancer therapy. Further development of L6 as an anti-tumor-targeting agent would benefit from the development of a murine model. However, initial attempts to develop such a model were hampered by our inability to generate antibodies against the murine homologue of the L6 antigen, M-L6. Here we describe the preparation of the mAb 12A8, which was raised against murine thymic epithelial cells, the tissue distribution of the murine antigen recognized by 12A8, the cloning of a cDNA encoding the 12A8 target antigen, and the demonstration that this antigen is M-L6. Using H-L6/M-L6 chimeric proteins, we show that the region of the M-L6 protein recognized by mAb 12A8 corresponds to the region of H-L6 recognized by mAb L6. There are five amino acid differences in the regions of the H-L6 and M-L6 proteins recognized by L6 and 12A8, respectively. We further mapped the protein epitope recognized by L6 by individually exchanging each of these residues in H-L6 with the corresponding residue found in M-L6. Substitution of the single H-L6 residue Leu122 with Ser resulted in the H-L6 mutant HL6-L122S which failed to bind L6. The HL6-L122S mutant also failed to bind 12A8.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1995

Competing HMOs collaborate to improve preventive services.

BACKGROUND: In July 1993, an unusual collaboration developed between competing managed care plans and with competing primary care clinics as part of a federally funded research grant (IMPROVE from the Agency for Health Care Policy and Research). The goal of this collaboration is to scientifically test the ability of an health maintenance organization (HMO) to improve the delivery of eight adult preventive services by training and facilitating the use of continuous quality improvement and prevention systems by contracted private primary clinics. METHODOLOGY: In order to conduct this effectiveness study, it was necessary for two HMOs to come to a structural and functional understanding of how to operate jointly. Investigators recruited 44 private clinics for a randomized controlled trial in which 22 are being assisted in improving the process used to deliver these preventive services and 22 are being left alone as comparison clinics. The intervention is a train-the-trainer and consultation approach focused on clinics as collaborating customers. The comparison will be based on repeated surveys of patients and clinic personnel as well as chart audits to measure changes in systems and prevention rates. SUMMARY: Although this project was made possible by a number of unusual favorable factors, it can serve as a model for support of the clinician leadership that is essential to true health care delivery reform.

Adult↗

PubMed1995

The effect of iron in formula milk after 6 months of age.

Ninety two normal birthweight infants aged 6 months entered a double blind controlled trial which compared a follow on formula milk with no added iron against the same formula milk containing 1.2 mg of iron per 100 ml. There was no significant difference in the social class or demographic characteristics of the two treatment groups or in the proportion of each group completing the trial. There was no difference between the two groups in the quantity of milk taken but the amounts taken lessened between 6 and 18 months of age. There was no difference between the two groups with respect to mean haemoglobin and median serum ferritin at 6, 9, 12, 15, and 18 months of age. Very few infants developed iron deficiency anaemia in either group but there was a tendency for serum ferritin levels to fall between 6 and 18 months of age in both groups. The results suggest that iron added to follow on milk was not an important source of dietary iron in the infants studied.

Anemia, Iron-Deficiency↗

PubMed1995

Childhood living arrangements and adult children's relations with their parents.

We examine the relationship of childhood living arrangements to adult child-parent relations. Compared with adult children raised in intact families, adult children whose parents divorced have less frequent contact with their parents and report a lower-quality relationship with their parents. We observe these negative effects for both custodial and noncustodial parents, although the effects are larger for noncustodial parents. Remarriage of the custodial parent tends to offset the negative impacts of divorce on relations with the custodial parent and to amplify the negative impacts on relations with noncustodial parents. Further, the longer the adult child lived apart from the parent, the weaker the relations with noncustodial parents.

Adaptation, Psychological↗

PubMed1994

Recognition of trophoblasts by gamma delta T cells.

The juxtaposition of maternal and fetal tissues in the hemochorial placenta has led to speculation that maternal recognition of fetal Ags present on trophoblasts might play an important role in reproductive biology. We report here for the first time such recognition of trophoblasts by T lymphocyte hybridomas representative of certain cells present in the maternal decidua. Trophoblast recognition is TCR dependent and is mediated by members of the V gamma 1+ subset of gamma delta T lymphocytes, a population that we previously have shown to be associated with heat shock protein-60 reactivity. Recognition occurred in experiments in which trophoblast clones or freshly prepared trophoblasts were used and requires cell-cell interaction. Although the maternal-fetal immune relationship typically has been cast in terms of an allograft, the T cell recognition of trophoblasts as described herein is not MHC-restricted, inasmuch as freshly prepared trophoblasts from beta 2-microglobulin-deficient mice were found to be stimulatory. Furthermore, the trophoblast ligand that mediates this recognition is probably a conserved mammalian molecule, because a human trophoblast cell line is also stimulatory. Our findings suggest a novel form of T cell recognition, and may provide an enhanced understanding of the maternal-fetal immune relationship.

Animals↗

PubMed1994

Binding of antidepressants to human brain receptors: focus on newer generation compounds.

Using radioligand binding assays and post-mortem normal human brain tissue, we obtained equilibrium dissociation constants (Kds) for 17 antidepressants and two of their metabolites at histamine H1, muscarinic, alpha 1-adrenergic, alpha 2-adrenergic, dopamine D2, serotonin 5-HT1A, and serotonin 5-HT2 receptors. Several newer antidepressants were compared with older drugs. In addition, we studied some antimuscarinic, antiparkinson, antihistamine, and neuroleptic compounds at some of these receptors. For the antidepressants, classical tricyclic antidepressants were the most potent drugs at five of the seven receptors (all but alpha 2-adrenergic and 5-HT1A receptors). The chlorophenylpiperazine derivative antidepressants (etoperidone, nefazodone, trazodone) were the most potent antidepressants at alpha 2-adrenergic and 5-HT1A receptors. Of ten antihistamines tested, none was more potent than doxepin at histamine H1 receptors. At muscarinic receptors antidepressants and antihistamines had a range of potencies, which were mostly weaker than those for antimuscarinics. From the in vitro data, we expect adinazolam, bupropion, fluoxetine, sertraline, tomoxetine, and venlafaxine not to block any of these five receptors in vivo. An antidepressant's potency for blocking a specific receptor is predictive of certain side effects and drug-drug interactions. These studies can provide guidelines for the clinician in the choice of antidepressant.

Antidepressive Agents↗

PubMed1994

A thymic stromal cell line supports in vitro development of surface IgM+ B cells and produces a novel growth factor affecting B and T lineage cells.

A thymic stromal cell line with a medullary phenotype (Z210R.1) supported the differentiation of surface IgM+ B cells when cocultured with fetal liver cells in vitro. Conditioned medium (CM) from this cell line supported the long-term growth of a B cell line (NAG8/7) isolated from cocultures and enhanced the proliferation of unfractionated thymocytes to suboptimal concentrations of anti-CD3 antibodies in vitro. Biological assays of the CM detected interleukin-7 (IL-7) but not IL-1, IL-2, IL-3, IL-4, IL-6, Steel factor (SCF), leukemia inhibitory factor (LIF), or macrophage or granulocyte colony-stimulating factors (M-CSF or G-CSF). The failure of recombinant IL-7 to maintain the long-term growth of NAG8/7 cells and the inability of anti-IL-7 antibodies to significantly affect the response of either NAG8/7 cells or thymocytes to CM suggested the presence of one or more other cytokines in the CM. Analysis of concentrated CM fractionated by anion exchange chromatography revealed a single peak of activity in the NAG8/7 assay with an elution profile that was distinct from IL-7. Two peaks of activity were detected in the thymocyte response to anti-CD3 antibodies; one corresponded to IL-7 and the other corresponded to the same fractions that stimulated NAG8/7 cells. The second peak of thymocyte stimulatory activity could not be inhibited by neutralizing anti-IL-7 antibodies. In addition to producing a cytokine with unique properties, this thymic stromal cell exhibits a functional homology to bone marrow or fetal liver stromal cells not previously appreciated.

Animals↗

PubMed1993

Breast cancer chemoprevention. Tamoxifen: current issues and future prospective.

Intervention clinical trials are under way to address whether tamoxifen can prevent breast cancer development. This effort is based on laboratory evidence that tamoxifen interferes with the initiation and promotion of mammary cancer, clinical evidence of decreased breast cancer incidence in the opposite breast of women participating in tamoxifen adjuvant breast cancer trials, and a favorable toxicity profile of tamoxifen providing reasonable assurance of drug safety when used in a population without cancer. The apparently favorable effects of tamoxifen on lipid metabolism and bone mineral density provide additional impetus to this evaluation. Potentially life threatening toxicity of thromboembolism and development of a second cancer remain concerns. With respect to implications of such clinical trials, even upon successful study completion, difficult issues will remain; these issues include the potential for interaction between tamoxifen and dietary fat reduction (also proposed as potential breast cancer prevention), the cost and cost-effectiveness of wide scale (or selective) implementation of positive results, and the generalizability of study results to socioeconomically disadvantaged and racial and ethnic minority populations that historically have been under-represented in medical clinical trials. These important issues should be addressed concurrently as large-scale prevention trials go forward to optimize the practical utility of efficacy data obtained.

Breast Neoplasms↗

PubMed1993

Tobacco mosaic virus infection of transgenic Nicotiana tabacum plants is inhibited by antisense constructs directed at the 5' region of viral RNA.

Antisense (AS) versions of two 51-nucleotide (nt) sequences near the 5' end of tobacco mosaic virus (TMV) RNA have been shown to inhibit in vitro translation of the adjacent gene that encodes both the 126- and 183-kDa proteins. These DNA fragments have been cloned into the binary vector, pMON530, such that either the nopaline synthase (Nos) promoter or cauliflower mosaic virus (CaMV) 35S RNA promoter is used to drive synthesis of the corresponding sense and AS RNAs. Transgenic Nicotiana tabacum cv. Xanthi nn plants containing these constructs were challenged with TMV. Plants expressing the AS orientation of a 51-nt TMV leader sequence, under the control of the CaMV 35S promoter, were found to be resistant to infection when inoculated with up to 100 times the concentration of TMV which produced severe infections in control plants. Systemic accumulation of TMV RNA and progeny virus was diminished 15 to 30-fold in these plants. Accumulation of the viral coat protein was diminished 6 to 7-fold implying a selective inhibition of TMV replication.

Base Sequence↗

PubMed1993

A novel cytokine-responsive cell surface glycoprotein defines a subset of medullary thymic epithelium in situ.

A hamster mAb (10.1.1), raised against long term cultures of uncloned thymic stromal cells, selectively labeled a subpopulation of medullary stromal cells in situ. By ultrastructural and phenotypic criteria, the stromal cells labeled by this mAb were judged to be epithelial. Although some of the 10.1.1+ epithelial cells were reticular, others were globular and some were associated with structures resembling Hassal's bodies. Ultrastructural immunohistochemistry suggested that 10.1.1 labeling of some of the epithelial cells was preferentially associated at areas of epithelial cell contact with adjacent thymocytes. Reactivity of thymic stromal cells with this antibody was developmentally regulated. A few scattered 10.1.1+ cells were observed at day 14 of gestation, and there were progressive increases in both the extent and intensity of 10.1.1 labeling evident through birth. One thymic stromal cell line, Z210.1, exhibited low levels of constitutive reactivity with this antibody. Exposure to IL-1 resulted in enhanced 10.1.1 reactivity of this cell line, with little, if any, additional response to TNF-alpha or IFN-gamma. Under the same conditions, ICAM-1 expression by this cell line was elevated in response to IL-1, TNF-alpha, or INF-gamma. Immunoprecipitation of detergent lysates prepared from Z210.1.7 cells exposed to IL-1 24 h before cell surface iodination identified a cell surface protein with a molecular mass of about 92 kDa under nonreducing conditions and about 95 kDa under reducing conditions. Digestion of 10.1.1 immunoprecipitates with N-glyconase resulted in a small (5 kDa) reduction in molecular mass. The molecule recognized by the 10.1.1 mAb was distinct from ICAM-1, which possessed a molecular mass of 100 kDa (nonreduced) and 110 kDa (reduced), and also displayed a smaller N-glyconase-resistant molecular mass (65 to 85 kDa).

Age Factors↗

PubMed1993

T cell receptor delta gene mutant mice: independent generation of alpha beta T cells and programmed rearrangements of gamma delta TCR genes.

T cells bearing T cell receptor (TCR) gamma and delta chain heterodimers are first generated early in ontogeny. They form distinct subsets that differ in their TCR repertoires and tissue distribution. Disruption of the mouse TCR C delta gene segment by a gene targeting method caused the complete loss of T cells bearing TCR gamma delta chains, but had little or no effect on the development of T cells bearing TCR alpha beta chains. The analyses of TCR gamma and delta genes in the mutant mice suggest that intracellular mechanisms acting at the level of DNA rearrangement play key roles in the differential gamma and delta gene rearrangements and in the generation of the highly restricted junctional sequences during fetal thymic development.

Animals↗

PubMed1993

The topography of muscle activity in quantitative EEG.

Ten normal preadolescent subjects were studied on three occasions with quantitative EEG topography: two sessions recorded EEG that was free of artifact, but during the third the subjects were instructed to clench their teeth and tighten their faces to produce muscle artifact. The sessions were then compared for stability of various frequencies at standard scalp electrode sites. The posterior electrodes were stable among sessions for frequencies up to 24 Hz; the anterior electrodes were less stable, and above 24 Hz there were no stable electrode sites. Muscle artifact contaminates anterior electrode sites more than posterior sites, making the posterior scalp electrodes superior for studying beta activity in quantitative EEG. Frequencies above 24 Hz are contaminated at all sites and therefore cannot be assessed reliably in the presence of muscle artifact.

Adolescent↗

PubMed1993

AASCIN strategic plan--1993-1998.

A long-standing commitment to planned growth and development are essential for the AASCIN to be effective in influencing the direction of spinal cord injury (SCI) nursing. Recognizing these needs, a long-range planning initiative was supported by the Board of Directors in March, 1990. A task force was charged with the responsibility for outlining the future of the AASCIN through the development of a five-year strategic plan. The long-range planning initiative was divided into two segments. First, a Delphi Study was developed to obtain membership input into AASCIN's priorities. Once this data was collected, the Strategic Planning Task Force synthesized the results of the study and developed a five-year AASCIN strategic plan. The purpose of this article is to describe the process and content of the proposed AASCIN strategic plan. The report begins with a brief description of the Delphi Survey, which forms the foundation for the strategic plan. Since the strategic plan needs to be congruent with the organization's mission statement and goals, the organizational plan of AASCIN is presented. Lastly, a brief summary of how the organization proposes to use this strategic planning document is provided.

Forecasting↗

PubMed1993

Toward the design of a new bowel care chair for the spinal cord injured: a pilot study.

Bowel care is a critical aspect of daily living for person with disabilities; ineffective bowel care can lead to severe and costly complications. Staff, patients, and caregivers have often found existing bowel care chairs to be inadequate. These chairs are frequently unsafe, inconvenient, and ineffective for showering and bowel elimination. Because bowel care procedures can be lengthy, proper seating posture and comfort is necessary to prevent pressure ulcers. Patient falls is another common problem, occurring during transfer, transport, or during actual bowel care/shower procedures. There are over 200,000 persons with spinal cord injuries (SCI) in the United States today. The majority of these patients have neurogenic bowels, requiring bowel care an average of three times a week. Each bowel care procedure takes 30 minutes to 3 hours to complete. Advances in bowel care chair design would significantly impact on quality of life, self-esteem, and physical well-being of persons with SCI. Enhanced design would also improve the safety, effectiveness, and efficiency of nurses and caregivers who perform bowel care procedures. An interdisciplinary research team, comprised of an industrial designer, a nurse, two physicians, and a human factors psychologist collaborated to address this important problem. Three bowel care chairs, commonly used in SCI, were evaluated using a combination of videotaping, still photography, and questionnaires. Based on this data, performance criteria for the design of an optimal bowel care chair design were developed.

Ergonomics↗

PubMed1993

Grading cervical dysplasia with AgNORs using a semiautomated image analysis system.

Colposcopic biopsies were classified according to previously established criteria by a group of three pathologists interested in cervical pathology. Ten cases were identified in each of the following five groups: normal, koilocytosis, low grade squamous intraepithelial lesions (CIN 1), high grade squamous intraepithelial lesions (CIN 2) and high grade squamous intraepithelial lesions (CIN 3). The Crocker technique was used to stain the sections cut 3 microns thick. With ths silver stain the nucleolar organizer regions (NORs) are stained black and referred to as AgNORs. It has been shown that malignant and premalignant changes in cells produce an increase in AgNORs. In each case eight images were captured using a 100x oil-immersion objective and stored in a Datacube Maxvideo system as 512 x 480 pixels in an 8-bit grayscale per image. The images were processed using the NeoPath field-of-view computer to detect the AgNORs and nuclei by using grayscale mathematical morphology algorithms. Color overlays of the AgNORs and nuclei were created using segmentation algorithms. The results show that it is possible to differentiate between low grade squamous intraepithelial lesions (CIN 1) and high grade squamous intraepithelial lesions (CIN 2 and CIN 3) taken together; however, there is no difference between low grade squamous intraepithelial lesions (CIN 1) and koilocytosis. The results support the concept that dysplasia cannot be classified effectively into three grades and that low grade squamous intraepithelial lesions (mild dysplasia [CIN 1]) is indistinguishable from koilocytosis.

Analysis of Variance↗