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PubMed1992

Analysis of conserved domains and sequence motifs in cellular regulatory proteins and locus control regions using new software tools for multiple alignment and visualization.

With the tremendous expansion of molecular sequence data in recent years, multiple alignment is arguably one of the two most important analytic techniques (the other being fast database searching). A number of useful approaches to this problem have previously been developed, but often they are limited to only a subset of multiple-alignment applications and cannot easily deal with the complex structural organization seen in an increasing number of sequences. For example, a single sequence may contain several domains of different evolutionary origins, and the multiplicities and relative ordering of these domains may be quite different among related sequences. Here we describe an integrated set of interactive Unix tools that combines several multiple-alignment techniques with traditional "dot-plot" visualization to provide a flexible environment for approaching complex sequence analysis problems. We apply these tools to the identification and characterization of "catalytic" domains in ras and rho/rac GTPase-activating proteins, to "Src homology" (SH2, SH3) domains in cytoplasmic signaling proteins, to repetitive sequence motifs in the alpha and beta subunits of protein prenyltransferases, and to regulatory DNA sequences in the locus control region of the beta-globin gene cluster.

Alkyl and Aryl Transferases↗

PubMed2006

Pulse!!--A virtual learning space project.

Game-based technology structured within an epistemic framework is revolutionizing learning. Intersecting military simulation technologies with modern pedagogical education practices, Pulse!! offers an epistemic framework for optimizing cognitive and psychomotor skills in clinical practices. Its intelligent authoring system is an integrated, fully immersive, interactive virtual learning simulation for civilian and military health care practitioners, providing opportunities to make mistakes and repeat actions.

Computer Simulation↗

PubMed2006

Radiologic estimation of hematoma volume in intracerebral hemorrhage trial by CT scan.

BACKGROUND AND PURPOSE: Therapeutic intervention during the early stages of an intracerebral hemorrhage (ICH) might have value in improving clinical outcomes. During the 73-site International Recombinant Activated Factor VII Intracerebral Hemorrhage Trial, CT techniques were used to monitor the change in hematoma volume in response to treatment. The use of CT imaging technology served 3 functions: to provide accurate measurements of the change in hematoma volume, intraventricular volume (IVH), and edema volume; to evaluate the use of CT scans as a predictor of patient outcomes; and to demonstrate that hematoma volume can serve as a surrogate marker for ICH clinical progression. METHODS: The multicenter clinical trial received institutional review board approval and obtained informed consent from the patient or a legally acceptable representative (waived in a few cases of incapacity, according to local and national regulations). CT scans were used to quantify volumes of hemorrhage and to monitor evolution over a 72-hour period in patients with ICH treated with placebo or 40, 80, or 160 microg/kg of recombinant activated factor VII (rFVIIa). CT image data were transmitted digitally to an imaging laboratory and analyzed by 2 readers masked to patient and treatment data, by using Analyze software, a fully integrated toolkit for interactive display, processing, and measurement of biomedical image data. The use of this software enabled the evaluation of intraclass variability of CT scan interpretations. RESULTS: Interpretations of ICH and IVH volumes of CT scans in patients treated in this study showed minimal intraclass variability. Variability was greatest for interpretations of edema volume. CONCLUSION: These CT assessments of lesions could have value in future early hemostatic interventions in ICH patients.

Cerebral Hemorrhage↗

PubMed2006

Healthy lifestyle behaviors among older U.S. adults with and without disabilities, Behavioral Risk Factor Surveillance System, 2003.

INTRODUCTION: Little is known about the relationship between healthy behaviors and the prevalence of chronic diseases in older adults with disabilities. This study examines the prevalence of selected healthy lifestyle behaviors related to chronic diseases among adults aged 65 years and older with and without disabilities. METHODS: Data from the 2003 Behavioral Risk Factor Surveillance System (BRFSS) were used to assess having a healthy weight and six behaviors: current cigarette smoking status, consumption of at least one alcoholic beverage daily, consumption of at least five fruits or vegetables daily, physical activity during the average week, influenza immunization in the past year, and lifetime pneumococcal immunization. RESULTS: People with a disability were less likely than people without a disability to have a healthy weight (28.5% vs 37.2%) and to engage in the recommended level of weekly physical activity (14.7% vs 26.2%). However, people with a disability were more likely than those without a disability to be nonsmokers (91.8% vs 89.9%), to consume up to one alcoholic beverage daily (95.1% vs 91.5%), to have received their influenza immunization in the past year (72.7% vs 69.0%), and to have received a lifetime pneumococcal immunization (72.1% vs 63.0%). There was no difference between people with and without a disability in the prevalence rates of consuming at least five fruits or vegetables daily. CONCLUSION: The prevalence of having a healthy weight and six chronic-disease related behaviors among adults aged 65 years and older varies by disability status and by specific modifiable lifestyle behavior. Screening older adults with and without disabilities and counseling them about health behaviors should be integrated into every interaction between older adults and their health care providers to potentially lower the rates of morbidity and mortality related to chronic diseases in the later years.

Aged↗

PubMed1991

Ovulatory dysfunction.

Ovulation is the result of a perfectly balanced and coordinated function of endocrine, paracrine, and autocrine systems. Any disruption in the delicately coordinated interaction between the integrated components of the hypothalamic-pituitary-ovarian axis may lead to ovulatory dysfunction, a multifactorial entity. The widening scope of knowledge regarding physiology of the reproductive processes as well as rapid development of new diagnostic methods and therapeutic procedures necessitates the continued reassessment and identification of factors leading to ovulatory dysfunction and the design of safe therapy for this condition. The combined use of serial ultrasonography and estradiol measurements should be the standard method of ovulation induction monitoring. The identification of high-risk groups prior to the initiation of ovulation induction regimens must also be taken into consideration if we want to improve pregnancy rate and reduce the incidence of hyperstimulation to a minimal level.

Abnormalities, Drug-Induced↗

PubMed1986

[Family interventions in crisis: a clinical case].

The authors make a clear difference between the traditional pattern of the psychiatric emergency and the interactional and more integrating conceptualization of the crisis' state. In an ecosystemic perspective they chiefly pay attention to the relation context in which the designated patient and his family are living. They make this clear by describing how the admission to the hospital of a "designated patient" has been avoided by the help of an intervention in the crisis' family and how they have been helped in gathering their resources during a critical period of their life-cycle.

Acculturation↗

PubMed1989

Elementary processes of response selection mediated by distinct regions of the striatum.

The relative contributions of the medial and lateral caudate putamen to performance of a visual reaction time task were compared by examining the effects of unilateral ibotenate-induced lesions to these regions in the rat. Different groups of rats were trained to respond either towards (Discrimination 1) or away from (Discrimination 2) unpredictable, brief visual stimuli presented to either side of the head. Lateral striatal lesions produced a strong spatial bias towards the side of the lesion but left the latency for the initiation of responses to the visual cues unchanged. By contrast, the medial striatal lesions resulted in a smaller degree of spatial response bias but a significant slowing of initiation latency to the side contralateral to the lesion. These effects were irrespective of the side of the stimulus presentation and thus represent response-related impairments. The lesions were further dissociated in their effects on responding inappropriately to task requirements. These results demonstrate a double dissociation of behavioral effects of lateral and medial striatal damage that can be used to infer the operation of distinct elementary processes of response output within a single task. They are important not only in demonstrating functional effects of hypothetical segregated parallel corticostriatal loops but also in showing that these loops must interact to produce integrated performance.

Acetylcholinesterase↗

PubMed1988

Transforming DNA sequences of human hepatocellular carcinomas, their distribution and relationship with hepatitis B virus sequence in human hepatomas.

Several related human transforming DNA sequences, hhc, and a putative normal liver homologue, c-hhc, have been molecularly cloned from the genomic DNAs of individual African and Asian hepatomas and from normal liver respectively. hhcM (Mahlavu) and hhcK3 (Korean), but not c-hhc, transformed NIH3T3 cells in DNA-mediated gene transfer assays. Transformed cells were found tumorigenic in athymic NIH Swiss nu/nu mice. In view of recent epidemiological studies implicating hepatitis B virus (HBV) infection early in life as causative for the eventual development of primary hepatocellular carcinoma in humans in Southeast Asia, the Far-East, and certain areas of Africa, we hereby analyzed the relationship between these hhcs and HBV in a survey of 20 hepatomas for DNA sequences homologous to hhcM and HBV by sequential hybridizations against [32p]hhcM and [32p]HBV probes. hhcM related DNA sequence were found highly amplified in 80% of the 20 hepatomas but HBV DNA sequence was rare or low. hhcM lends itself as a marker for human hepatomas. However, overall results indicated that patients with integrated HBV DNA sequences showed high copy number of hhcM sequence. Furthermore, EcoR1-restricted hepatoma DNAs showed that HBV and hhcM DNA sequences resided at different fragments in hepatomas. Our results suggest that HBV contributes to hepatocarcinogenesis probably via an activation mechanism involving possibly an integration or transient interaction of HBV DNA with hepatocyte DNA sequences, leading to recombination and eventual amplifications of the hhcM sequence in Mahlavu.

Animals↗

PubMed1988

New technologies in chemistry instrumentation: the basis for clinical chemistry automation.

The analytical and operational capabilities of clinical chemistry analyzers will continue to evolve as new technologies are developed. This will lead to increasingly greater automation and enhanced ease of use. However, it will be important for the laboratorian to understand these technologies in order to effectively integrate them and interact with them in the health care environment.

Automation↗

PubMed1985

Interactions between severely mentally retarded students and other students in integrated and segregated public school settings.

Severely mentally retarded target students (n = 245) from 14 school districts in 9 states were observed in integrated and segregated social groups in 1981 and 1982. The rate of social bids directed by these students to other students and by other students to them was significantly higher in integrated social groups than in segregated social groups. In addition, a higher rate of positive bids was directed by nonretarded students to severely retarded students in comparison to bids from other handicapped students in integrated groups. Nonretarded students responded to social bids from severely retarded students more frequently than did other retarded students. The implications of the results of integration for severely retarded students are discussed in terms of increased social interaction opportunities and the generalized usage of social skills.

Adolescent↗

PubMedDate not supplied

[Cortico-subcortical systems of conditioned reflex activity].

Experimental data are presented on dynamic rearrangment of corticofugal influences on subcortical structures during conditioning and conditioned performance, as well as data on the transition of diffusive influences, to selective ones. The mechanisms of plastic rearrangment of subcortical influences in the course of consolidation of the conditioned reflex are discussed on the basis of cortical-reticular and cortical-striate interactions. The significance of subcortical interactions in the integrative brain activity and in the organization of behaviour is discussed. Facts are presented on synchronization of several rhythms in rhythmical activity in the strio-thalamo-cortical system in the process of achievement of conditioned reflexes.

Brain↗

PubMed1967

The neurological information network of the National Institute of Neurological Diseases and Blindness.

The National Institute of Neurological Diseases and Blindness (NINDB) has the responsibility of trying to alleviate the morbid and mortal effects of all the diseases of the nervous system and the special senses including speech, hearing, and vision. The information problem facing the NINDB is only a fraction of the total information problem of the biomedical community, but it is probably representative. The NINDB information audience has a core of about 19,000 persons, 10 percent of whom are nonclinical research scientists; 10 percent of whom are engaged in patient care, teaching, and some research; 12 percent in training (post doctoral); and 68 percent chiefly involved in the care of patients. In addition, there is an unknown number of other interested scientists. Fifty to eighty thousand journal articles, an unknown number of technical reports, and other items produced each year are potentially valuable to this group. The exact needs of each subgroup must be identified and ways developed to deliver the required information quickly, accurately, and in an easily useable form. NINDB has undertaken a large information program as a service to the biomedical community to help cope with these information problems. This program is to serve the needs of the practicing physician, the research scientist, and NINDB program analysis and planning. The Neurological Information Network is the core effort of the program.The Neurological Information Network envisions large units incorporating both information storage and retrieval and information analysis. These will be in universities with strong biomedical libraries where there are ongoing research programs in some area relevant to NINDB responsibilities. These units are to be integrated and will interact with each other and with the National Library of Medicine to avoid duplication of work. In addition to their own information analysis activities, the major documentation centers will be able to support information analysis satellites at other research centers where specific categorical research programs are underway.

Blindness↗

PubMed1983

Suppression of the simian virus 40 tumorigenic phenotype in hybrid cells formed from simian virus 40- and adenovirus 2-transformed hamster embryo cells.

Hamster cells transformed by adenovirus 2 (Ad2) or simian virus 40 (SV40) have different tumorigenic phenotypes. In the present study, somatic cell hybrids formed from Ad2- and SV40-transformed hamster cells were used to determine whether possible interactions between the integrated viral genomes would influence the tumorigenic phenotype of hybrid transformed cells. These somatic cell hybrids were of two types, one expressing both Ad2 and SV40 T-antigens and the other expressing only SV40 T-antigens. Tumor induction by hybrid cells that expressed both Ad2 and SV40 T-antigens was reduced in adult syngeneic hamsters and abrogated in adult allogeneic hamsters. These results indicate that the tumorigenic phenotype of transformed somatic cell hybrids that contain both the Ad2 and SV40 genome is governed by the genetic expression of Ad2. This expression may alter the ability of SV40-transformed hamster cells to resist the immunologically nonspecific defenses of the host.

Adenoviridae↗

PubMed1984

The nature and function of granulopoietic microenvironments.

A significant volume of reviewed literature in combination with observations presented here suggest that fibroblastic reticulum cells of the hematopoietic stroma may play a decisive role in the regulation of granulopoiesis. The histology of both bone marrow and spleen demonstrates an association between granulopoiesis and fibroblastic reticulum cells. Using in vitro cultured primary fibroblastic cells from murine bone marrow (BM) as antigenic source, we have prepared a hybridoma cell line secreting a monoclonal antibody (mAb) to fibroblastic reticular cells of the nonlymphoid domains in the spleen and BM. The mAb (ER-HR1) was demonstrated to exclusively detect primary fibroblastic cells cultured from spleen and bone marrow and in situ reticular cells with characteristic dendritic morphology and a dispersed distribution pattern. These reticular cells had extensive ramifications in the hemopoietic parenchyma. With the exception of some sparse fibroblastic cells in the dermis of the skin, the mAb did not react with any other cell type or extracellular substance elsewhere in the mouse, nor did it cross-react with human hemopoietic tissues. Support for a role of fibroblastic reticular cells in the regulation of granulopoiesis was obtained from in vitro studies. Primary BM fibroblasts produced granulocyte-macrophage colony stimulating activity (CSA). In contrast, we have been unable to detect CSA production by BM macrophages. Rather, we have found that BM macrophages deplete exogenous CSA from their culture medium. It is concluded that CSA may be produced by fibroblastic cells in adherent BM cultures and that the low CSA levels detected in their medium is due to depletion of fibroblastic cell-derived CSA by macrophages. We conclude that fibroblastic reticulum cells of the hemopoietic stroma carry unique antigenic determinants and together with macrophages, endothelial cells, and lymphocytes contribute to a complex network of cellular interactions providing an integrated microenvironmental control of granulopoiesis.

Animals↗

PubMedDate not supplied

Epidemiology for community health nursing: an interactive computer assisted instruction program.

Epidemiology and its application to community health nursing is an essential concept for baccalaureate nursing students. To facilitate student learning, nursing faculty chose to use computer assisted instruction (CAI) as an adjunct teaching-learning strategy. An interdisciplinary team, including nursing content specialists and a computer programmer, produced an interactive CAI that integrated epidemiologic content, community health nursing practice, and learning-theory principles. Contents of the program modules are described, and program strategies used to enhance learning are delineated. Evaluation of the program indicated students (N = 106) believed the content was clearly explained and preferred learning epidemiology through combining classroom learning with CAI rather than through textbook reading assignments.

Community Health Nursing↗

PubMed1993

Analysis of structure-function relationships in the platelet membrane glycoprotein Ib-binding domain of von Willebrand's factor by expression of deletion mutants.

We have used a series of Escherichia coli-expressed deletion mutants of the glycoprotein (GP) Ib-binding domain of von Willebrand factor (vWF) to study the structural basis of its function. In addition to the prototypic molecule (rvWF441-733), we constructed 11 mutants; seven had deletions of sequence on the amino- and/or carboxyl-terminal side of the Cys509-Cys695 intrachain disulfide loop, and four had limited deletions inside the loop. Other cysteine residues in addition to 509 and 695, when present in the corresponding native sequence, were mutated to glycine; all molecules were purified in the oxidized as well as reduced and alkylated state. The smallest species retaining the ability to interact with GP Ib in the absence of modulators was the oxidized rvWF508-696; the latter, as well as rvWF441-696, became inactive after reduction and alkylation. In contrast, all the other fragments with deletions outside of the loop, but extending at least to residue 700, showed better binding to platelets after reduction and alkylation than when the Cys509-Cys695 disulfide bond was oxidized. Any limited deletion of sequence inside the loop caused complete loss of GP Ib-binding function both in the absence or in the presence of botrocetin, and this persisted even after reduction and alkylation. In contrast, all mutants with intact sequence between residues 509 and 695 bound to GP Ib in the presence of botrocetin, regardless of whether the 2 cysteine residues were oxidized or reduced and alkylated. Ristocetin, unlike botrocetin, appeared to have no effect in modulating the binding of any of the expressed fragments to platelets. Our findings suggest that the GP Ib-binding domain of vWF contains multiple interaction sites, but integrity of the sequence 509-695 is important for function.

Amino Acid Sequence↗

PubMed1996

[Family emotional climate of pain patients].

Personal clinical experiences in an interdisciplinary pain clinic and their integration into family interaction theories led to a concept of an explorative study of chronic pain patients. Therefore 32 patients and their spouses were investigated with the "family-environment-scale" (by Moos and Moos 1981, adapted by Schneewind et al. 1985). Most of the couples showed agreement with regard to familial solidarity, combined with few expressions of anger and conflict and low achievement orientation. The typical profile of these factors led to one group with the "positive-emotional family climate", in contrast to one group with the "normative-authoritative family climate". In addition, a potentially new factor was described as a so-called "symbiotic family climate". The latter constellation was on the one hand quite similar compared to the "positive-emotional climate", but differed on the other hand because of the small amount of structural control. The interference of these family climate profiles with the process of chronification for pain patients is discussed.

Adult↗

PubMed1996

Interleukin-4-specific signal transduction events are driven by homotypic interactions of the interleukin-4 receptor alpha subunit.

Interleukin-4 (IL-4) exerts its effects through a heterodimeric receptor complex (IL-4R), which contains the IL-4R(alpha) and gamma(c) subunits. IL-4R(alpha) also functions with other partner subunits in several receptor types, including the IL-13 receptor. To examine the roles of the individual subunits within IL-4R complexes, we employed a chimeric system that recapitulates native IL-4R function as verified by the activation of the kinases, JAK1 and JAK3, and induction of STAT-6. When a mutant gamma(c) subunit in which the four cytoplasmic tyrosines were converted to phenylalanine was paired with the cytoplasmic domain of the IL-4R(alpha) chain, specificity within the JAK-STAT pathway was not altered. Signaling events were examined further in cells expressing the IL-4R(alpha) chimera alone without the gamma(c) chimera. Ligand-induced homodimerization of these receptors activated the IL-4 signaling program despite the absence of gamma(c), including induction of JAK1 and STAT-6, phosphorylation of the insulin-related substrate 1 and cellular proliferation. Thus, homotypic interactions of the IL-4R(alpha) subunit are sufficient for the initiation and determination of IL-4-specific signaling events, and such interactions may be integral to signaling through IL-4R complexes.

Animals↗