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PubMed2006

Comparative analysis of the paired immunoglobulin-like receptor (PILR) locus in six mammalian genomes: duplication, conversion, and the birth of new genes.

Manyaspects of the immune system are controlled by homologous cell surface receptors that mediate inhibitory and activating pathways. The paired immunoglobulin-like receptor (PILR) locus at 7q22 encodes both PILRA, an inhibitory receptor, and PILRB, its activating counterpart. Mouse Pilrb1 is a novel immune system regulator, and its ligand Cd99 participates in the recruitment of T-cells to inflamed tissue. We characterized the PILR locus in six mammalian genomes and investigated the structure and mRNA expression of human PILRB. Synteny at the PILR locus is conserved in the human, chimpanzee, dog, mouse and rat genomes. The absence of the PILR locus in opossum and chicken genomes suggests it arose after the divergence of placental and nonplacental mammals. In humans, a Williams-Beuren syndrome-related segmental duplication has created a complex chimeric transcript representing the predominantly expressed form of PILRB. Unlike PILRA, PILRB transcripts were detected in a wide variety of tissues including cells of the lymphoid lineage. In the mouse genome, a second activating gene, Pilrb2, and six pseudogenes were found. Extensive gene duplications in the rat genome have resulted in at least 27 Pilrb genes and or pseudogenes. Abundant gene duplication events involving novel CD99-related genes were also detected in the rat genome. In addition to duplication, we show that gene conversion has played a persistent role in the evolution of the PILR genes. Overall, we demonstrate that the PILR locus is dynamically evolving via multiple evolutionary mechanisms in several mammalian genomes.

Animals↗
PubMedDate not supplied

Positioning and the discursive construction of categories.

Psychological phenomena are semiotic, so the best model for understanding them must be 'conversation'. Psychiatric conversations are dominated by complaints. In dealing with them the structure of the consequential conversation must be subjected to 'positioning analysis' to reveal the dynamics of rights and duties among the speakers.

Humans↗
PubMed1986

Nicotine, cotinine, and anabasine inhibit aromatase in human trophoblast in vitro.

Epidemiologic studies suggest that women who smoke have lower endogenous estrogen than nonsmokers. To explore the possible link between cigarette smoking and decreased endogenous estrogens, we have examined the effects of constituents of tobacco on estrogen production in human choriocarcinoma cells and term placental microsomes. In choriocarcinoma cell cultures, nicotine, cotinine (a major metabolite of nicotine), and anabasine (a minor component of cigarette tobacco) all inhibited androstenedione conversion to estrogen in a dose-dependent fashion. Removal of nicotine, cotinine, and anabasine from the culture medium resulted in the complete reversal of the inhibition of aromatase. In the choriocarcinoma cell cultures, a supraphysiologic concentration of androstenedione (73 microM) in the culture medium blocked the inhibition of aromatase caused by nicotine, cotinine, and anabasine. In preparations of term placental microsomes, nicotine, cotinine, and anabasine inhibited the conversion of testosterone to estrogen. Kinetic analysis demonstrated the inhibition to be competitive with respect to the substrate. These findings suggest that some nicotinic alkaloids directly inhibit aromatase. This mechanism may explain, in part, the decreased estrogen observed in women who smoke.

Anabasine↗
PubMed1994

Self-induced correction of the genetic defect in tyrosinemia type I.

A mosaic pattern of immunoreactive fumarylacetoacetase (FAH) protein was found in liver tissue in 15 of 18 tyrosinemia type I patients of various ethnic origins. One additional patient had variable levels of FAH enzyme activity in liver tissue. In four patients exhibiting mosaicism of FAH protein, analysis for the tyrosinemia-causing mutations was performed in immunonegative and immunopositive areas of liver tissue by restriction digestion analysis and direct DNA sequencing. In all four patients the immunonegative liver tissue contained the FAH mutations demonstrated in fibroblasts of the patients. In the immunopositive nodules of regenerating liver tissue one of the mutated alleles apparently had reverted to the normal genotype. This genetic correction was observed for three different tyrosinemia-causing mutations. In each case a mutant AT nucleotide pair was reverted to a normal GC pair.

Amino Acid Metabolism, Inborn Errors↗
PubMedDate not supplied

The meaning of the nurse's presence during childbirth.

OBJECTIVE: The purpose of this exploratory study was to develop new understandings of what it means to women in labor for a nurse to be present during childbirth. DESIGN: Hermeneutic inquiry was used to explore the phenomenon of nursing presence during childbirth. The purpose of questioning in hermeneutic phenomenology is to stimulate thoughtful reflection and deeper exploration of the subject's experiences. PARTICIPANTS/ SETTING: Six women from an urban center in Canada volunteered to share their experiences of childbirth through conversations with the research team. DATA ANALYSIS: Audio-taped, transcribed interviews were analyzed along with the reflections of the research team. RESULTS: Women attribute multiple meanings to the care provided by intrapartum nurses. However, what stood out in these women's accounts was that a nurse's presence was the way in which a nurse was "there" for them and was a very important part of their childbirth experience. CONCLUSIONS: Women's experiences of a nurse's presence cannot be understood apart from the institutional structures and work processes that shape their experiences. Further research is needed to explicate how hospital procedures, administrative structures, and medical practices enable or constrain the presence of the intrapartum nurse.

Canada↗
PubMed1997

In vivo indicators of pathologic ruminal sulfide production in steers with diet-induced polioencephalomalacia.

Two groups of 3 120-160-kg Holstein steers were fed a diet high in carbohydrate and low in long fiber and either with or without added sodium sulfate. Prior to and during the course of feeding the experimental diet, the concentrations of rumen hydrogen sulfide gas and rumen fluid sulfide were determined by a simple sulfide detector tube method and by sulfide-selective electrode, respectively. Other measurements included rumen fluid pH, blood creatine kinase, and blood sulfhemoglobin. Two of the 3 steers fed the high-sulfate diet developed signs and lesions of polioencephalomalacia. Clinical signs included episodic ataxia and blunted or absent menace reaction. Increased ruminal H2S gas concentrations occurred in all 3 steers consuming the diet with added sulfate. The onset of clinical signs coincided with the onset of elevated H2S concentrations. These increases were 40-60 times the values measured in the steers consuming the diet without added sulfate. In contrast, increases in rumen fluid sulfide concentrations usually rose to 4 times that of control steers. The steers fed an identical diet but without added sulfate exhibited no signs or lesions of polioencephalomalacia and no elevations of sulfide in rumen gas or fluid. All steers had a modest decrease in rumen fluid pH associated with the transition to the concentrate diet. No significant changes were observed in any of the blood measurements of any of the steers. An additional pair of steers was fed the experimental diet with or without added sulfate to compare the ruminal H2S gas concentrations estimated by H2S detector tubes with those estimated by a different method of analysis utilizing charcoal trapping of H2S, conversion to sulfate, and measurement of the sulfate. Both methods yielded comparable estimates of H2S concentration. Overall, these data indicate that changes in rumen gas cap H2S concentrations are larger than changes in rumen fluid sulfide concentration and the estimation of rumen gas cap H2S concentration may be a practical approach to detecting pathologic increases in ruminal H2S gas. This simple, rapid, minimally invasive method should be useful for estimating the H2S content of ruminal gas under field conditions.

Animal Feed↗
PubMed1979

Visualization of multidimensional spectra in flow cytometry.

Flow data from a cell sorter have been processed by hardwired circuits which include amplification, discrimination, coincidence requirements, peak sensing and holding, A-D conversion, and a computerized pulse height analysis with storage of the spectra obtained. Two dimensional spectra can be stored directly in memory, on tape and disk. Three and four parametric cellular events can be recorded on line during the flow measurement in a sequential mode on tape for subsequent recall. Simple processing of these data can be performed for displaying of two dimensional projections from these multidimensional spaces based on threshold conditions for the remaining parameters. Interfaced transmission of the stored data to a large scale computer enables more sophisticated data analysis. Data reduction by means of a multidimensional probability analysis has been carried out in order to transfer the spectra to a computerized picture system for display. This system creates perspective two-dimensional images from a three-dimensional data space. Frequency can be converted into grey levels. Hard copy in color (color as the third dimension and color intensity as frequency) simplifies the visualization of multiparametric flow data sets.

Animals↗
PubMed1999

Prevalence of mild apparent mineralocorticoid excess in Mennonites.

UNLABELLED: We have studied an unusual patient with mild low-renin hypertension due to a homozygous mutation in the HSD11B2 gene (PNAS 95:10200-10205, 1998). The patient came from an inbred Mennonite family, and though the mutation identified her as an AME patient, she had a normal birth weight and did not demonstrate the typical features of AME, such as hypokalemic alkalosis, low birth weight, failure to thrive, poor growth, and in many cases nephrocalcinosis. Biochemically, typical patients with AME have abnormal cortisol metabolites and an exceedingly diminished ability to convert [11-3H]cortisol to cortisone. In this patient with mild AME, the conversion of cortisol to cortisone was 58% compared to 0 to 6% in typical AME patients, while the normal conversion is 90 to 95%. Molecular analysis of the HSD11B2 gene of this patient showed a homozygous mutation in codon 227 (P227L). We studied this Mennonite population for the prevalence of the P227L mutation. Our hypothesis was that this mild form of AME would be prevalent in the somewhat inbred Mennonite population to which the patient belongs. Our proposed study was 1) to determine if there are other cases of this mild form of AME, and 2) to establish the heterozygote frequency of the mutation in the Mennonites. RESULTS: We did not detect any additional cases of mild AME. We detected 15 carriers of the P227L mutation out of 445 Mennonites, resulting in a heterozygote frequency of 0.03. CONCLUSION: Since this is an inbred population, the chance of two heterozygotes marrying would be 0.001, which is 1 in 1000 people. This population is known to have large families and therefore the possibility of having an affected child is high. The population consists of 2000 members and we have discovered one affected patient. Thus, there might be one other patient in this population.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2003

Family members' narrated experiences of communicating via video-phone with patients with dementia staying at a nursing home.

We studied the experience of family members who communicated via video-phones with elderly demented patients who were either staying at a home for temporary respite care or living in a nursing home. The study was based on qualitative data from seven interviews. The interviewees each had three or more months' experience with a video-phone. The open interviews were transcribed. Content analysis showed that video-phone conversations made the relatives of patients at nursing homes more involved in the caring process and that conversation via the video-phone was a different way of communicating. Video-phone conversations with demented patients were in some cases more focused and of better quality than face-to-face conversations. In most cases the video-phone conversations required the assistance of staff at the home in order to be meaningful. Video-phones have the potential to become useful tools for family members caring for elderly relatives.

Aged↗
PubMed1998

Comparison of amino acid sequence of the C-terminal domain of insulin-responsive glucose transporter (GLUT4) in livestock mammals.

The nucleotide sequence of cDNA coding the 38-amino acid of the C-terminal domain of insulin-responsive glucose transporter (GLUT4) was determined by the method of reverse transcription-polymerase chain reaction in the sheep, goat and pig, and compared with that of bovine which have been shown to have a unique amino acid conversion of Asn508 to His. The deduced amino acid sequence was completely identical in the three species, and did not have the amino acid conversion at position 508. Western blot analysis confirmed that an antiserum raised against a rat C-terminal peptide cross-reacted efficiently with GLUT4 of these livestock mammals.

Amino Acid Sequence↗
PubMed2006

Redefining disease? The nosologic implications of molecular genetic knowledge.

How will developments in genetic knowledge affect the classification of disease? Leaders in genetics have suggested that knowledge of the role of genes in disease can determine nosology. Diseases might be defined by genotype, thus avoiding the limitations of more empirical approaches to categorization. Other commentators caution against disease definitions that are detached from the look and feel of disease, and argue for an interplay between genotypic and phenotypic information. Still others attribute nosologic change to social processes. We draw on an analysis of the scientific literature, our conversations with genetics clinicians, and reviews of patient organization Web sites to offer a revised interpretation of the nosologic implications of molecular genetic knowledge. We review the recent histories of three diseases--hemophilia, Rett syndrome, and cystic fibrosis--to argue that nosologic change cannot be explained by either biologic theories of disease etiology or sociologic theories of social tendencies. Although new genetic information challenges disease classifications and is highly influential in their redesign, genetic information can be used in diverse ways to reconstruct disease categories and is not the only influence in these revisions. Ironically, genetic information is likely to play a central role in producing a new, but still empirical, classification scheme.

Cystic Fibrosis↗
PubMed2003

TEM00 terawatt amplification by use of micro-optic spatial mode conversion.

Micro-optic technology is used in a terawatt multipass Ti:sapphire amplifier to convert high-multimode, 532-nm radiation from an unstable resonator Nd:YAG laser into a TEM00 amplified output without sacrificing the amplifier-to-pump energy conversion efficiency. Experimental measurements and Fourier analysis of the spatial mode show a 3.8-fold increase in the peak irradiance and an order-of-magnitude improvement in the spatial contrast.

Journal Article↗
PubMed2006

Multiple user considerations and their implications in medical error reporting system design.

OBJECTIVE: The study examined the differences between physicians and clinical assistants in their preferences for a statewide medical error reporting system. BACKGROUND: Medical error reporting systems have been proposed as a means for studying the causes of medical error. Knowledge of user similarities and differences is needed for the development of design guidelines for medical error reporting systems. METHOD: Separate focus groups composed of 8 physicians and 6 clinical assistants (physician clinical support staff) were conducted. One-hour focus group meetings were conducted via toll-free teleconference lines one to two times per month for 9 months. All conversations were audiotaped and transcribed for analysis. An inductive content analysis was conducted. RESULTS: Eighty-six major and minor themes emerged. Differences between physicians and clinical assistants included rules and regulations governing the use of the system, the medium of reporting, and aspects of the organization that may affect reporting levels. CONCLUSIONS: Although physicians and clinical assistants shared similar preferences and beliefs surrounding error reporting, there were differences that need to be considered if medical error reporting systems are to be effective. APPLICATION: To successfully deploy a medical error reporting system, the system itself must be designed for the potential users. This study uncovered previously underappreciated issues that should be incorporated into the design and implementation process. Actual or potential applications of this research include the improvement of the design and implementation of medical error reporting systems to account for the needs of different types of users.

Attitude of Health Personnel↗
PubMed2000

[Perception of nurses about risk factors for nosocomial infection].

A study was undertaken in a pediatric teaching hospital to evaluate the nurses understanding about risk factors for nosocomial infections. The data were obtained in interviews with nurses of the emergency room, intensive and semi-intensive units. The analysis of the meaning of the conversation permitted the identification of the following risk factors: inadequacy of the hospital design and construction, deficiency of care equipment and supplies, understaffing, lack of education and training to the healthcare workers and orientation to the patients family.

Attitude of Health Personnel↗
PubMedDate not supplied

Optimization of block-floating-point realizations for digital controllers with finite-word-length considerations.

The closed-loop stability issue of finite-precision realizations was investigated for digital controllers implemented in block-floating-point format. The controller coefficient perturbation was analyzed resulting from using finite word length (FWL) block-floating-point representation scheme. A block-floating-point FWL closed-loop stability measure was derived which considers both the dynamic range and precision. To facilitate the design of optimal finite-precision controller realizations, a computationally tractable block-floating-point FWL closed-loop stability measure was then introduced and the method of computing the value of this measure for a given controller realization was developed. The optimal controller realization is defined as the solution that maximizes the corresponding measure, and a numerical optimization approach was adopted to solve the resulting optimal realization problem. A numerical example was used to illustrate the design procedure and to compare the optimal controller realization with the initial realization.

Analog-Digital Conversion↗
PubMed1988

Effect of personal oral hygiene on bleeding interdental gingiva. Histologic changes.

A previous study demonstrated that the combination of subgingival scaling and improved oral hygiene resulted in a reduction of clinical and histological signs of interdental gingival inflammation, changes that were associated with a cessation of interdental gingival bleeding. The present study compared, histologically, the interdental tissues of bleeding sites with sites that initially bled but had been converted to nonbleeding by an oral hygiene program alone. Morphometric analysis of interdental gingiva demonstrated that conversion from bleeding to nonbleeding was associated with a significant reduction in the inflamed connective tissue component. This study showed that an oral hygiene program consisting of toothbrushing and interdental cleaning could significantly reduce interdental inflammation, and that bleeding determinations monitored the effects of this therapy.

Adult↗
PubMed1999

The effects of long-term administration of recombinant bovine somatotropin (Posilac) and Synovex on performance, plasma hormone and amino acid concentration, and muscle and subcutaneous fat fatty acid composition in Holstein-Friesian bull calves.

The effect of recombinant somatotropin (rbST), Synovex (Syn), and their combination (rbST+Syn) on intact male calves was examined in an experiment that lasted an average of 238 d. Holstein-Friesian bull calves were allotted to one of four subtreatments (n = 14/treatment) in a factorial arrangement. There were two levels of rbST (0; rbST) and two levels of the estrogenic growth promoter Synovex (0; Syn). The rbST was administered once every 2 wk as injections of 500 mg of Posilac. Synovex (C and S) was implanted at 90-d intervals. The animals were fed for ad libitum consumption a diet with a metabolizable energy concentration of 11.7 MJ/kg DM and 15% crude protein. The hot carcasses were weighed after the removal of kidney, pelvic, and cod fats, which were weighed separately. The 12th rib cut was saved for analysis. Average daily gain and feed conversion efficiency were increased by rbST treatment by 9% (P < .005) and 10% (P < .016), respectively. There was no significant effect of Syn treatment, nor was there a rbST x Syn interaction. The proportion of the fat of the large depots in the carcass was reduced by 34% (P < .0001) and in the longissimus muscle by 32% (P < .16) owing to the rbST treatment. The plasma concentrations of GH, insulin, and thyroxin were increased by rbST treatment (P < .001, P < .01, and P < .03, respectively). The concentration of IGF-I was not affected. Synovex had no effect on plasma hormone concentration. Plasma essential and nonessential amino acid concentrations were reduced by 14 and 9%, respectively, when rbST was injected. Concentrations of cholesterol and fatty acids in muscle and subcutaneous fat were not affected (P > .072) by the rbST treatment. Synovex increased the monounsaturated fatty acids (MUFA), and the combinaton of Syn with rbST reduced polyunsaturated fatty acid (PUFA) concentration in the longissimus muscle (at the 12th rib). The reduced muscle fat content of the rbST-treated animals was associated with a trend toward an increase in polyunsaturated fatty acids.

Adipose Tissue↗
PubMed1994

Autoreactive T cell-dependent polyclonal hypergammaglobulinemia in mantle cell lymphoma.

We investigated the mechanism of polyclonal B cell differentiation in mantle cell lymphoma (MCL) using peripheral blood mononuclear cells (PBMC) from a patient with MCL in leukemic stage presenting polyclonal hypergammaglobulinemia. Patient T cells not only responded to autologous non-T cells but induced polyclonal production of IgG in vitro. Flow cytometric analysis of PBMC showed the increased conversion of CD4+ T cells from the naive to the memory state. We propose the possible mechanism that autoreactive T cells may be involved in polyclonal B cell differentiation in this monoclonal B cell disorder.

B-Lymphocytes↗