Subjectivity and objectivity in the analyst.
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Ego↗
Biomedical subjects
M Berg
Publications and source records attributed to M Berg.
Miniaturization of a functional transcription assay in yeast (human progesterone receptor) in the 384- and 1536-well plate format.
Miniaturization of high throughput screening assays to high-density microplate formats (384 or 1536 wells) is currently the focus of research activity in modern drug discovery facilities. In this article, we describe the adaptation of a fluorescence-based functional transcription assay in yeast for assessing modulators of human progesterone receptor to the 384- and 1536-well microplate format, comparing the experimental results to those obtained in the well-established 96-well format. The experiences gained from the optimization of the liquid-handling procedures and the miniaturization of an enzyme assay (beta-galactosidase) were implemented. Thus optimized pipetting protocols were developed to perform a reporter gene assay in yeast in microplate formats of higher density. In the functional transcription assay in yeast, the reporter gene expression showed the expected dependence on the ligand's dose and affinity in principle in all three microplate formats. For the first time, this assay system has been established in the 1536-well microplate format using CyBi-Well 96/384/1536 as the liquid-handling unit. The comparison of the signal:background ratios showed a lower sensitivity of the assay in the microplate formats of higher density. This study is an example of a successful miniaturization of a yeast cell-based assay to high-density plate formats on the basis of a careful adaptation procedure and optimized liquid-handling conditions.
Cloning, Molecular↗
Pregnancy and diabetes--a hermeneutic phenomenological study of women's experiences.
The aim of this article is to describe women's experiences of being pregnant and having insulin-dependent diabetes mellitus (IDDM), particularly regarding what the crucial elements of the experience are during pregnancy. A qualitative method with a hermeneutic phenomenological approach was used. The subjects were 14 pregnant women with IDDM, of whom eight were primiparous and six multiparous. They were interviewed during pregnancy concerning their experience of 'being controlled by blood glucose levels for the child's sake'. The child makes demands, with consequences which are divided into two main themes: objectification, including loss of control and an awareness of having an unwell 'risky body'; and exaggerated responsibility, including constant worry, constant pressure and constant self-blame. The results present a challenge to every midwife, physician or other health professional involved in the care of pregnant women with diabetes. They have an important role in mediating understanding of how risks to such women during pregnancy and childbirth can be minimized by normalizing the blood glucose level. At the same time, they should point out the fact that most women with IDDM today have healthy babies. This could reduce negative feelings. The women should also be supported and encouraged in the normal transition to motherhood.
Adaptation, Psychological↗
[Rett syndrome--an odd handicap affecting girls. A current 25-year follow-up in Western Sweden].
Rett syndrome, a complicated neurodevelopmental disorder exclusively affecting girls in early childhood, is now known to be one of the major worldwide causes of severe mental retardation in females. Although internationally unknown until the mid-1980s, under another designation it had been observed in Sweden since the early 1960s. The article consists in a review of current clinical, neurobiological and genetic knowledge of the syndrome, and a systematic penetration of data collected from the follow-up of a west Swedish series of 54 female patients, 5-57 years of age. Mortality in the series was 17 percent, with a median age at death of 24 years. In most cases death was sudden and unexpected.
Adolescent↗
Restoration of lymphoid populations in a murine model of X-linked severe combined immunodeficiency by a gene-therapy approach.
X-linked severe combined immunodeficiency (XSCID) is a life-threatening syndrome in which both cellular and humoral immunity are profoundly compromised. This disease results from mutations in the IL2RG gene, which encodes the common cytokine receptor gamma chain, gamma(c). Previously, we generated gamma(c)-deficient mice as a murine model of XSCID. We have now used lethally irradiated gamma(c)-deficient mice to evaluate a gene therapeutic approach for treatment of this disease. Transfer of the human gamma(c) gene to repopulating hematopoietic stem cells using an ecotropic retrovirus resulted in an increase in T cells, B cells, natural killer (NK) cells, and intestinal intraepithelial lymphocytes, as well as normalization of the CD4:CD8 T-cell ratio and of serum Ig levels. In addition, the restored cells could proliferate in response to interleukin-2 (IL-2). Thus, our results provide added support that gene therapy is a feasible therapeutic strategy for XSCID. Moreover, because we used a vector directing expression of human gamma(c) to correct a defect in gamma(c)-deficient mice, these data also indicate that human gamma(c) can cooperate with the distinctive cytokine receptor chains such as IL-2Rbeta and IL-7Ralpha to mediate responses to murine cytokines in vivo.
Animals↗
Menin represses JunD-activated transcription by a histone deacetylase-dependent mechanism.
Recently the multiple endocrine neoplasia type 1 (MEN-1) tumor suppressor gene was cloned. MEN-1 encodes a nuclear protein, called menin, of hitherto unknown function. In order to investigate the biological function of menin we employed the yeast two-hybrid system to identify menin-interacting proteins. Here we report that menin functions as a transcriptional repressor through interaction with the transcription factor JunD. The interaction is mediated via the N-terminal transcription activation domain of JunD, and the C-terminal part of menin. In transient co-transfection experiments, expression of menin leads to specific repression of JunD transcriptional activity, which is dependent on the integrity of the menin C-terminal region. C-Terminal truncations of the protein not only abolish repression, but increase JunD transcriptional activity, implying the existence of a functional domain separate from the JunD-binding region. Menin-mediated repression is relieved by the histone deacetylase inhibitor trichostatin A, indicating that deacetylation of histones is an essential component of this repression mechanism, as has recently been demonstrated for the retinoblastoma protein. Missense, in-frame deletions, frameshift and nonsense mutations lead to inactivation of menin or possibly to truncated proteins. This would result in loss of repression of menin/JunD target genes, as well as non-target genes through indirect mechanisms, deregulation of cellular growth control and endocrine tumorigenesis.
Down-Regulation↗
Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma-mediated signaling.
Using the coiled-coil region of Stat5b as the bait in a yeast two-hybrid screen, we identified the association of Nmi, a protein of unknown function previously reported as an N-Myc interactor. We further show that Nmi interacts with all STATs except Stat2. We evaluated two cytokine systems, IL-2 and IFNgamma, and demonstrate that Nmi augments STAT-mediated transcription in response to these cytokines. Interestingly, Nmi lacks an intrinsic transcriptional activation domain; instead, Nmi enhances the association of CBP/p300 coactivator proteins with Stat1 and Stat5, and together with CBP/p300 can augment IL-2- and IFNgamma-dependent transcription. Therefore, our data not only reveal that Nmi can potentiate STAT-dependent transcription, but also suggest that it can augment coactivator protein recruitment to at least some members of a group of sequence-specific transcription factors.
CREB-Binding Protein↗
Chromosomal organization and nucleotide sequence of the genes coding for the elongation factors G and Tu of the apple proliferation phytoplasma.
Genes coding for elongation factors G (fus) and Tu (tuf) of the non-culturable apple proliferation (AP) phytoplasma were cloned and sequenced. Arrangement of these genes and identification of the ribosomal protein gene rps7 upstream of the fus gene suggest a transcriptional organization similar to that of the streptomycin operon of Escherichia coli and other bacteria. The fus and tuf genes from other tested phytoplasmas were found to be similarly linked as in the AP agent. Thus, it is likely that they show a similar chromosomal arrangement. This organization would be in contrast to that of the phylogenetically distinctly different culturable mollicutes of the genus Mycoplasma in which the tuf and fus genes are separately transcribed.
Amino Acid Sequence↗
Development during single IVP of bovine oocytes from dissected follicles: interactive effects of estrous cycle stage, follicle size and atresia.
Previous work suggests that a number of factors such as follicle size, day of estrous cycle, and level of atresia influence the developmental potential of bovine oocytes in vitro. To understand better the interactions of these factors, 1299 follicles > or =3 mm in diameter were dissected from ovaries of synchronized dairy cows on four days (d2, d7, d10, or d15) during the estrous cycle. The oocyte from each follicle was collected and matured, fertilized, and cultured singly to d8 (d0 of culture = IVF). Control follicles (302) were similarly dissected and processed from an ovary pair randomly collected from the abattoir on each slaughter day. Results showed that development to blastocyst was greater in oocytes collected during phases of follicular growth (d2 and d10) than those collected during phases of follicular dominance (d7 and d15; 44.8% vs. 36.0%, respectively: P < 0.001) over all follicle size categories (3-5 mm, 6-8 mm, 9-12 mm and > or =13 mm). Oocyte competence tended to increase with increasing follicle size (P < 0.1). Follicular cells from follicles containing an oocyte that developed to morula or greater by d8 (484 samples) were analyzed by flow cytometry to measure the level of apoptosis. Results showed an increase in mean percent apoptotic cells in subordinate follicles (18.65 +/- 0.86 over all size categories), particularly those of medium size (25.55 +/- 2.2 for 6-8 mm size follicles; P < 0.001), during the dominance phase compared to growth phase (9.25 +/- 0.95 over all sizes; P < 0.05). These results show a significant affect of the stage of estrous cycle on both oocyte competence and levels of follicular atresia.
Animals↗
Borna disease virus infection in racing horses with behavioral and movement disorders.
Borna disease virus (BDV) is a neurotropic agent with capacity to infect and cause neurological disease in a broad range of warmblooded hosts including horses, sheep, cattle, cats, and possibly also humans. The epidemiology of BDV is largely unknown. However, it is likely that subclinically infected animals may represent potential virus reservoirs. In two groups of Swedish racing horses, one clinically healthy and one consisting of horses with diffuse neurological signs, the BDV seroprevalence was 24.5% and 57.7%, respectively. BDV RNA was detected in peripheral blood mononuclear cells in 8 out of 28 (28.6%) investigated horses, the majority of the BDV RNA-positive horses belonging to the group with neurological signs. There was a close relationship between the Swedish equine BDV isolates and previously reported equine BDVs in Europe. Our results point to an association of BDV infection with atypical disease patterns in horses such as diffuse mental and gait disturbances. These findings may be of importance for the understanding of the epidemiology of BDV infections in animals and man.
Amino Acid Sequence↗
Peripheral and intracerebral T cell immune response in cats naturally infected with Borna disease virus.
Borna disease virus (BDV) is a neurotropic agent with capacity to cause encephalomyelitis in a wide range of animal species, including horses and cats. Recent studies also point to a link between BDV and human neuropsychiatric disorders. The pathogenesis of Borna disease (BD) has been proposed to be immune-mediated, mainly through the effects of cytotoxic T cells. We used flow cytometric analysis in order to characterize the peripheral and intracerebral T cell immune response in cats naturally infected with BDV. Our results show the presence of two different CD8+ cell populations (CD8+low and CD8+high) in the blood, spleen and brain of these cats. In the brain, CD8+low cells predominated over CD8+high cells. Since CD8+low cells have been suggested to represent a non-MHC-restricted T cell population, the recruitment of such cells to the brains of BDV-infected cats could possibly be of importance for the clearance of virus from neurones.
Animals↗
Patient care information systems and health care work: a sociotechnical approach.
Those who face the difficulties of developing useful patient care information systems (PCISs) often stress the importance of 'organizational issues'. Building upon recent sociological insights in the construction and use of information technologies for (health care) work, this paper underscores the importance of these insights for the development and evaluation of these systems. A sociotechnical approach to PCISs in health care is outlined, and two implications of this empirically grounded approach for the practices of developing and evaluating IT applications in health care practices are discussed. First, getting such technologies to work in concrete health care practices appears to be a politically textured process of organizational change, in which users have to be put at center-stage. This requires an iterative approach, in which the distinctions between 'analysis', 'design', 'implementation' and 'evaluation' blur. Second, a sociotechnical approach sheds new light on the potential roles of IT applications in health care practices. It is critical of approaches that denounce the 'messy' and 'ad hoc' nature of health care work, and that attempt to structure this work through the formal, standardized and 'rational' nature of IT systems. Optimal utilization of IT applications, it is argued, is dependent on the meticulous interrelation of the system's functioning with the skilled and pragmatically oriented work of health care professionals.
Information Systems↗
The contextual nature of medical information.
Successful design of information systems in health care starts with a thorough understanding of the practices in which the systems are to function. In this paper, we discuss the nature of 'medical information' from a sociological perspective. We focus on the (im)possibilities of the utilization of primary health care data for secondary purposes such as research and administration. In much of the literature on EPRs, this secondary utilization is only seen to depend on the question whether the IT connections are in place. It is then simply a matter of selecting which information to transport and to where. In this article, we argue that this view of medical information is mistaken. Information should be conceptualized as always entangled with the context of its production. The disentangling of information from its production context is possible, but that entails work. We propose the following 'law of medical information': the further information has to be able to circulate (i.e. the more diverse contexts it has to be usable in), the more work is required to disentangle the information from the context of its production. The question that then becomes pertinent is; who has to do this work, and who reaps the benefits?
Decision Support Techniques↗
Commentary: studying maternal experiences of childbirth.
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Amnion↗
Stinging and rosacea.
A total of 32 rosacea patients (25 with the papulopustular type of rosacea and 7 with the erythematotelangiectatic type) and 32 healthy persons were single-blind tested with a solution of 5% lactic acid and pure water applied to their cheeks. Twenty-four patients and 6 controls reacted positively as "stingers" (p<0.001) in this objective test of sensitive skin. All 7 of the patients with erythematotelangiectatic rosacea, but only 17/25 with the papulopustular type, were stingers (n.s.). The reason why some patients react with subjective symptoms, such as itching, burning, stinging, prickling or tingling, is unclear. The findings in this study are not surprising, but do support the theory that impairment due to different stimuli, most likely because of vascular sensitivity, is a central mechanism in the aetiology of rosacea. The correlation between sensitive vessels and sensitive skin has, however, not yet been determined.
Adult↗
Bipolar ventricular far-field signals in the atrium.
In an attempt to evaluate the prevalence and predisposing factors of bipolar ventricular far-field oversensing, 57 patients were studied who had a Medtronic dual chamber pacemaker implanted (models 7940: n = 6; 7960i: n = 41; 401: n = 3; 8968i: n = 7) and bipolar atrial leads with a dipole spacing from 8.6 to 60 mm attached to various parts of the atrial wall (lateral/anterior: n = 30; appendage: n = 10; atrial septum: n = 10; floating: n = 7). Median bipolar sensing threshold for P waves was 4.0 mV (2.8-4.0 mV, lower and upper quartile) with standard leads and 0.35 (0.25-1.4) mV with single pass (VDD) devices. At the highest sensitivity available, 43 of 50 DDD pacemakers but only two of seven VDD systems detected intrinsic R waves in the atrium (P < 0.01). Ventricular far-field oversensing occurred at 0.5 mV in 28 (56%) and at 1.0 mV in 16 of 50 DDD units (32%), respectively, and there was one observation in a septal implant at a sensitivity of even 2.8 mV. With ventricular pacing, VDD systems were as susceptible to far-field signals as DDD pacemakers. Outside the postventricular blanking period (100 ms), evoked R waves were detected by 27 of 57 systems (47%) at maximum atrial sensitivity, by 10 (18%) at 0.5 mV, and by 2 (4%) at a setting of 1.0 up to 1.4 mV, respectively. There was no definite superiority of any lead position, there was a trend in favor of the atrial free wall for better intrinsic R wave rejection, but just the opposite was the case for paced ventricular beats. Bipolar signal discrimination tended to be higher with short tip-to-ring spacing (1 7.8 mm) but the difference to larger dipole lengths (30-60 mm) was not significant in terms of the R to P wave ratio and the overall far-field susceptibility. In summary, bipolar ventricular far-field oversensing in the atrium is common with short postventricular blanking times and high atrial sensitivity settings that may be warranted for tachyarrhythmia detection and mode switching. A potentially more discriminant effect of shorter dipole lengths (< or = 10 mm) remains to be tested.
Adult↗
Five-year follow-up of a bipolar steroid-eluting ventricular pacing lead.
Steroid-eluting pacing leads are known to attenuate the threshold peaking early after implantation. Long-term performance, however, is not yet settled. The lead design tested in this prospective study combines a 5.8-mm2 tip of microporous platinum-iridium with elution of 1.0 mg of dexamethasone sodium phosphate and tines for passive fixation (model 5024, Medtronic Inc.). In 50 patients (mean age 69 +/- 10 years), the electrode was implanted in the right ventricular apex. Follow-up was performed on days 0, 2, 5, 10, 28, 90, 180 and every 6 months thereafter for 5-years postimplant. At each visit, pacing thresholds were determined as pulse duration (ms) at 1.0 V and as the minimum charge (microC) delivered for capture. Lead impedance (omega) was telemetered at 2.5 V-0.50 ms, and sensing thresholds (mV) were measured in triplicate using the automatic sensing threshold algorithm of the pacemaker implanted (model 294-03, Intermedics Inc.). On the day of implantation, mean values were 0.10 +/- 0.03 ms, 0.12 +/- 0.03 microC, 758 +/- 131 omega, and 13.1 +/- 1.8 mV, respectively. Beyond 1-year postimplant, pacing thresholds did not vary significantly. Sensing thresholds and lead impedance values were stable during long-term follow-up. Five years after implantation, mean values were 0.23 +/- 0.11 ms, 0.24 +/- 0.07 microC, 670 +/- 139 omega, and 11.6 +/- 3.1 mV for pulse width and charge threshold, lead impedance, and sensing threshold, respectively, and all leads captured at 1.0 V with the longest pulse duration available (1.50 ms). It is concluded that the bipolar steroid-eluting tined ventricular lead showed stable stimulation thresholds, lead impedance values, and sensing thresholds for 5 years after implantation.
Adult↗
Mild carotid artery atherosclerosis: assessment by 3-dimensional time-of-flight magnetic resonance angiography, with reference to intravascular ultrasound imaging and contrast angiography.
BACKGROUND AND PURPOSE: Our aim was to evaluate the usefulness of 3-dimensional time-of-flight magnetic resonance angiography (3-D TOF MRA) in detection and quantification of mild atherosclerotic changes of carotid arteries with reference to intravascular ultrasound (IVUS) and contrast angiography. METHODS: TOF MRA at 1.5 T, IVUS, and selective digital subtraction angiography were performed on 31 extracranial carotid arteries of 27 patients (mean age, 52 years; age range, 17 to 75 years) undergoing neuroendovascular interventions. The atherosclerotic lesions were registered, and quantitative measurements of plaque thickness, luminal diameters, and diameter stenosis were independently performed for the imaging modalities. RESULTS: Among 170 arterial segments analyzed, IVUS revealed a total of 48 atherosclerotic lesions (mean diameter stenosis, 17%; range, 4% to 40%), only 25 of which were depicted on digital subtraction angiography. Analysis of the axial source images of TOF MRA resulted in sensitivity of 77% to 83% and specificity of 71% to 80% in lesion depiction for the 2 readers with reference to IVUS. The values of diameter stenosis measured from MRA and IVUS were closely interrelated (r=0.53 to 0.61, P<0.001). CONCLUSIONS: Three-dimensional TOF MRA is feasible and moderately accurate for evaluation of mild atherosclerotic changes of carotid arteries.
Adolescent↗