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Biomedical subjects

D L Nelson

Publications and source records attributed to D L Nelson.

At least 415 records · Page 23Linked to original sources

Eukaryotic chromosome transfer: linkage of the murine major histocompatibility complex to an inserted dominant selectable marker.

We have developed an approach for genetic analysis of the murine H-2 complex that has broad general applicability to the study of eukaryotic genome organization. We have used a retroviral vector to introduce a selectable marker into the mouse genome close to the major histocompatibility complex (MHC). Chromosomal segments containing large portions of the MHC from these donor cells have been transferred both to hamster and monkey cell recipients. The procedure involved the following steps. First, a murine cell line was multiply infected with a defective recombinant murine leukemia virus that contains the neomycin-resistance gene (a gene that confers resistance to G418). In this way, the neomycin-resistance gene was introduced at multiple sites in the mouse genome. Second, metaphase chromosomes, prepared from this infected cell population, were transferred to hamster cell recipients. Third, two G418-resistant transferents were identified that expressed murine H-2 antigens on their cell surface. These transferents were shown to contain a large segment of the murine MHC (H-2K and I regions) by DNA hybridization. The neomycin-resistance gene and the mouse MHC genes must be physically linked in these cells since they could be cotransferred from the hamster cells to monkey cells. Fourth, the murine cell carrying the neomycin-resistance gene near the MHC was identified from the original donor cell population. This cell will serve as a useful source of chromosome fragments for analysis of larger portions of the MHC. This series of steps can serve as a paradigm for the first steps in a detailed genetic analysis of any specific region of a mammalian genome to which one or more genes have already been mapped.

Animals↗

Burnout among physical therapists.

Burnout results in a decrease in job performance because of excessive work-related stress. This study assessed the presence of burnout among physical therapists and determined if potential organizational and personal causes of burnout could predict symptoms of burnout. One hundred and sixty therapists surveyed nationwide met the established criteria for inclusion in the study; 84 (53%) stated that they were currently experiencing feelings of burnout. Subjects were asked to respond to the frequency of their symptoms of burnout and the relevancy of the list of potential causes. A standard multiple regression equation was completed on each of the five dependent variables (symptoms) predicted by the eight potential causes of burnout, four of which were organizational in nature and four of which were personal in nature. Four out of the five symptoms of burnout were significantly predicted by different potential causes. Burnout experienced by physical therapists can have a detrimental effect on patients, therapists, and the facilities in which they are employed.

Analysis of Variance↗

[3H]5-Hydroxytryptamine binding sites: species and tissue variation.

The characteristics of spiperone inhibition of [3H]5-hydroxytryptamine [(3H]5-HT; [3H]serotonin) binding were examined in dorsal (DH) and ventral (VH) hippocampus, corpus striatum (CS) or caudate nucleus (CN), and frontal cortex (FC) in the rabbit, guinea pig, and cat. Some of the properties of spiperone inhibition of [3H]5-HT binding in these species were similar to the properties previously found in the rat. Spiperone was significantly more potent in DH, VH, and FC than in CS or CN. It produced shallow or biphasic inhibition curves, resulting in Hill slopes of less than 1.0. Nonlinear regression analysis of the data showed that the inhibition curves fit a two-site binding model significantly better than a one-site model in each brain region. The dissociation constants of spiperone for the high-affinity binding site (KH) for all the tissues and species, except cat FC and rabbit DH, were very close to those previously found in the rat (2-13 nM). However, the dissociation constants for the low-affinity binding site (KL) were different from those in the rat in all species and tissues examined, except cat FC and CS. The present data are consistent with the concept of multiple 5-HT1 binding sites and suggest the presence of at least two, and perhaps as many as three, groups of sites in the mammalian brain.

Animals↗

Differential laterality of hand function in right-handed and left-handed boys.

This study was designed to investigate differences in the degree of manual lateralization between right-handed and left-handed normal boys. Sixty-three 5, 7, and 9 year olds were tested on the Minnesota Rate of Manipulation Test (displacing subtest and turning subtest), the Finger Tapping Test, the Purdue Pegboard (placing subtest and assembly subtest), and the Southern California Motor Accuracy Test--Revised. Significant differences between right- and left-handed subjects were obtained on two of the six measures, and a third measure approached significance, with less lateralization among the left handers than among the right handers. Subsequent analyses indicated that differences in lateralization were significant or near-significant in the 5 and 7 year olds. By 9 years of age, right- and left-handed subjects no longer differed in the degree of laterality. Differences in degree of laterality, or the lack of such differences, between young right- and left-handed boys might be a function of the nature of the fine motor task or a function of the child's previous experience with the task.

Age Factors↗

Choice making in group and individual activity.

A guiding premise of occupational therapy practice is that it is beneficial to allow clients freedom of choice in selecting and participating in activities. This study examined subjects' affective responses to having or lacking freedom of choice in completing an activity and explored how those responses might differ when subjects did the activity in individual as opposed to group settings. Forty female undergraduate and graduate students participated in an origami activity under four different experimental conditions: a) individual--choice; b) individual--no choice; c) group--choice; and d) group--no choice. Afterward, each subject rated how she felt about herself while participating in the activity by using Osgood's semantic differential designed to elicit responses in terms of three affective factors: evaluation, power, and activity. Data analysis revealed an interaction between the two independent variables on the power factor such that subjects who were not permitted choice responded significantly differently from those who were permitted choice only in the group setting. Implications of this finding for occupational therapy practice are discussed.

Adult↗

Sequential versus simultaneous graphesthesia tasks in 6- and 10-year-old children.

Reported in the statistics of the Southern California Graphesthesia Test are significant sex differences for certain young age groups, with females scoring higher than males. In contrast, another study has reported that adult males scored higher than females on the same test. The purpose of this study was to examine the interaction between sex and age and to investigate a possible explanation for this interaction. Sixty-four normal children between the ages of 6.0 and 7.0 years, and 10.0 and 11.0 years were administered two graphesthesia tasks. One task was an adaptation of the Graphesthesia Test of the Southern California Sensory Integration Test (SCSIT). In this task, shapes were drawn sequentially on the palmar surface of the child's hand. A second task was devised whereby each of the same shapes was presented in a simultaneous manner, that is, the entire outline of each shape was pressed onto the palmar surface of the child's hand. Results indicated that for both tasks, younger boys performed relatively less ably than girls, but older boys equalled or surpassed the girls. At a level approaching significance, females scored relatively higher than males on the sequential task, and males scored relatively higher than females on the simultaneous task. However, this tendency toward an interaction between sex and the type of task does not fully explain the interaction between sex and age on graphesthesia tasks.

Age Factors↗

Effects of selected activities on affective meaning in psychiatric patients.

Occupational therapists have used activity analysis to ensure the therapeutic use of activities. Recently, they have begun to explore the affective components of activities. This study explores the feelings (affective responses) that chronic psychiatric patients have toward selected activities commonly used in occupational therapy. Twenty-two participating chronic psychiatric patients were randomly assigned to one of three different activity groups: cooking, craft, or sensory awareness. Immediately following participation, each subject was asked to rate the activity by using Osgood's semantic differential, which measures the evaluation, power, and action factors of affective meaning. Data analysis revealed significant differences between the cooking activity and the other two activities on the evaluation factor. The fact that the three activities were rated differently is evidence that different activities can elicit different responses in one of the target populations of occupational therapy. The implications of these findings to occupational therapists are discussed and areas of future research are indicated.

Activities of Daily Living↗

The Southern California Postrotary Nystagmus Test and electronystagmography under different conditions of visual input.

This study assessed the Southern California Postrotary Nystagmus Test (SCPNT)-stimulated nystagmus under three conditions of indoor illumination (bright, dim, and dark), and it studied the concurrent validity of SCPNT and electronystagmographic (ENG) measures of nystagmus duration and excursion. Eighteen adult subjects received three sets of rotations to the left under different lighting conditions in a counterbalanced order. The duration and excursion of the SCPNT were monitored under the bright and dim conditions, and ENG-recorded duration, excursion, frequency, slow-phase velocity, and average intersaccadic interval were measured under all three lighting conditions. No significant differences were found between nystagmus duration or excursion under the bright and dim conditions, but highly significant differences were found between the dark condition and the other two conditions. The correlation between ENG-recorded duration and SCPNT visually monitored duration across bright and dim conditions was .73, and the correlation for excursion was .24. These results suggest that occupational therapy researchers and clinicians need not question the validity of ENG recordings under different indoor lighting conditions, and suggest that the concurrent validity of ENG recordings and SCPNT measures requires more study.

Adolescent↗

Metaphase chromosome transfer of introduced selectable markers.

A general method for creating somatic cell hybrids which maintain chromosome segments by selection is described. To extend the technique of metaphase chromosome transfer to regions of the genome which do not carry a selectable marker, a retroviral vector has been employed to introduce the dominant selectable neo gene at many genomic locations in a population of murine cells. We have used such cells as donors in metaphase chromosome transfer experiments in which hamster and monkey cells were used as recipients. Cells acquiring a transferred chromosomal segment containing the neo gene were selected by growth in the presence of the drug G418. Hybridization to cloned interspersed repeat DNA sequences of the mouse was used to estimate the proportion of mouse DNA in each transferent. These experiments indicate that transferents produced in this manner contain 0.01 to 1.0% of the mouse genome. To analyze the organization of the DNA transferred to each recipient, we used Southern transfer hybridization of DNA from each transferent to a cloned mouse interspersed repeated DNA probe which did not cross-hybridize to hamster or monkey DNA. We found that each primary transferent gave a unique pattern of restriction fragments hybridizing to this probe. Secondary transferents from two independent primary transferents were compared by this technique. Each set of secondary transferents exhibited a hybridization pattern which resembled closely that of the primary transferent from which it was derived. However, a number of hybridizing DNA segments present in each primary transferent were absent in some of the secondary transferents. These results are most compatible with the view that an intact segment of the mouse chromosome surrounding the integration site of the retroviral vector can be transferred by the techniques used in this study. We believe this technique will be generally applicable to cells from many species, and will allow the study of chromosome regions previously refractory to analysis by chromosome transfer techniques.

Animals↗

A study of liver microsomal enzymes in rats following propoxur (Baygon) administration.

Groups of rats were given either propoxur, were left as untreated controls, or were given phenobarbital, DDT, chlordane or toxaphene which are known to induce liver microsomal detoxification enzymes. Microsomal enzyme activity was measured by testing the ability of liver homogenates to degrade EPN (O-ethyl O-(4-nitrophenyl) phenylphosphonothioate) to p-nitrophenol. The activity of aminopyrine-N-demethylase, cytochrome P-450 and p-nitroanisole-O-demethylase in liver homogenates of rats receiving propoxur was measured. Liver microsomal detoxification enzymes were not induced by propoxur exposure.

Aminopyrine N-Demethylase↗

Specificity of in vitro anti-influenza virus antibody production by human lymphocytes: analysis of original antigenic sin by limiting dilution cultures.

The fine specificity of the antibody produced in in vitro cultures of human lymphocytes stimulated with influenza virus was investigated. The antibody was specific for the stimulating type of virus in that cultures stimulated with type B influenza virus made little or no antibody to type A viruses and vice versa. There was a degree of cross-reactivity among the type A viruses, however, both within and between subtypes. In general, more antibody was made to the stimulating strain of virus than to heterologous strains, with the exception that cultures of mononuclear cells from four of five donors stimulated with A/Bangkok/79 (H3N2) made more antibody to A/Aichi/68 (H3N2) than to the stimulating virus, likely reflecting the original antigenic exposure of these donors. The specificity of this in vitro response was further investigated by using monospecific antibodies produced in limiting dilution cultures. Approximately 30% of the antiviral antibodies produced in these cultures bound to purified hemagglutinin, but only 7% bound to purified matrix protein. When antibodies stimulated with A/Bangkok/79 were analyzed for their binding to other H3N2 viruses, a variety of reactivity patterns was observed. Some antibodies were specific for A/Bangkok/79 and some bound to common determinants found on a number of H3N2 viruses. In addition, a number of antibodies were observed that did not bind to A/Bangkok/79 but did bind to earlier H3N2 viruses, demonstrating an extreme form of "original antigenic sin." A similar variety of reactivity patterns was observed when antibodies were tested for binding to heterotypic type A viruses or hemagglutinins. The results of the present experiments demonstrate that the fine specificity of an in vitro human antibody response can be analyzed by using limiting dilution cultures, and suggest that the fine specificity of the antibody response of an individual to a strain of influenza virus is affected by previous antigenic exposure of that individual.

Adult↗

Antigen-stimulated human B cell clones are committed to the production of a single class of antibody in vitro.

We have investigated the isotype(s) of antibody produced in vitro by antigen-stimulated human B cell clones. An analysis of the class(es) of antibody produced in multiple replicate cultures containing a mean of less than one precursor B cell per well was consistent with the hypothesis that individual B cell precursors produced a single class of antibody. This result was obtained by using cells isolated from either the peripheral blood or tonsils. Thus, under the culture conditions utilized, no intraclonal isotype switching was detected.

Antibodies, Viral↗

Metastatic cutaneous Crohn's disease.

A 16-yr-old boy and a 38-yr-old woman with Crohn's disease developed granulomatous dermatitis on the forearm and lower calf, respectively. Their lesions were clinically and histologically similar to those described in the small number of prior reports of "metastatic" cutaneous Crohn's disease. They were readily distinguished from those of other dermatologic conditions associated with Crohn's disease, such as pyoderma gangrenosum, erythema nodosum, and cutaneous polyarteritis nodosa. Appropriate clinical studies, biopsy specimens, and cultures are required, however, to exclude other forms of granulomatous disease that could occur coincidentally in a patient with Crohn's disease.

Adolescent↗

Mental representations for pictures and words: same or different?

Do pictures and their corresponding verbal labels activate common meaning representations? Alternatively, do pictures invariably act like words-in-context generating some but not all of the semantic content activated by their labels? These possibilities were evaluated in a cuing experiment in which the cues consisted of either pictures or their labels and the targets consisted of related words. Modality and cue presence-absence during the study trial were manipulated along with preexperimental measured-meaning set size and cue-target strength. The results indicated that as long as category size and relative strength were equal, pictures and words appeared to activate functionally identical semantic representations. However, this commonality should not be expected across all drawings of the same referent. A second experiment using rhyming words indicated that the phonemic representations activated by naming a picture or reading a word were identical. However, subjects were able to use visual information contained in the labels to facilitate retrieval.

Association Learning↗

Computer-assisted autoradiographic localization of subtypes of serotonin1 receptors in rat brain.

In vitro light microscopic receptor autoradiography was carried out to localize two subtypes of 5-HT1 receptors in certain regions of the rat central nervous system (CNS). The data were analyzed by computerized digital image processing to reveal subfields of high receptor densities within the septal area, the prefrontal and frontal cortex, and the hippocampus. The septum and hippocampus showed interesting localization of serotonin binding which can be subtyped into 5-HT1-A and 5-HT1-B sites. The differential localization of these sites may be helpful in shedding some light as to the functional significance of multiple serotonin receptors.

Animals↗

Limiting dilution analysis of Epstein-Barr virus-induced immunoglobulin production by human B cells.

The Epstein-Barr virus (EBV) is a herpes virus that has the capacity to infect human B cells and to induce them to secrete immunoglobulin (Ig). In the current experiments, Poisson analysis of limiting dilution cultures has been used to study the activation of human peripheral B cells by the B95-8 strain of EBV. Under the culture conditions used, 0.2-1% of peripheral blood B cells were activated by EBV to secrete IgM or IgG. In addition, when multiple replicate cultures containing limited numbers of B cells were tested for IgM and for IgG production, the precursors for IgM and IgG segregated independently; thus, individual B cell precursors matured into cells secreting IgM or IgG but not both classes of Ig. Additional experiments using limiting dilutions of EBV were undertaken to study the viral requirements for B cell activation. These studies indicated that B cell activation by EBV to produce Ig was consistent with a "one-hit" model and inconsistent with a "two-hit" model. Taken together, these results indicate that infection by one EBV virion is sufficient to induce a precursor peripheral blood B cell to secrete Ig and that only one isotype of Ig is then secreted.

Antibody Formation↗

Biochemical studies of the excitable membrane of paramecium tetraurelia. IX. Antibodies against ciliary membrane proteins.

The excitable ciliary membrane of Paramecium regulates the direction of the ciliary beat, and thereby the swimming behavior of this organism. One approach to the problem of identifying the molecular components of the excitable membrane is to use antibodies as probes of function. We produced rabbit antisera against isolated ciliary membranes and against partially purified immobilization antigens derived from three serotypes (A, B, and H), and used these antisera as reagents to explore the role of specific membrane proteins in the immobilization reaction and in behavior. The immobilization characteristics and serotype cross-reactivities of the antisera were examined. We identified the antigens recognized by these sera using immunodiffusion and immunoprecipitation with 35S-labeled ciliary membranes. The major antigen recognized in homologous combinations of antigen-antiserum is the immobilization antigen (i-antigen), approximately 250,000 mol wt. Several secondary antigens, including a family of polypeptides of 42,000-45,000 mol wt, are common to the membranes of serotypes A, B, and H, and antibodies against these secondary antigens can apparently immobilize cells. This characterization of antiserum specificity has provided the basis for our studies on the effects of the antibodies on electrophysiological properties of cells and electron microscopic localization studies, which are reported in the accompanying paper. We have also used these antibodies to study the mechanism of cell immobilization by antibodies against the i-antigen. Monovalent fragments (Fab) against purified i-antigens bound to, but did not immobilize, living cells. Subsequent addition of goat anti-Fab antibodies caused immediate immobilization, presumably by cross-linking Fab fragments already bound to the surface. We conclude that antigen-antibody interaction per se is not sufficient for immobilization, and that antibody bivalency, which allows antigen cross-linking, is essential.

Animals↗