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J Pehrson

Publications and source records attributed to J Pehrson.

12 recordsLinked to original sources

PNA interference mapping demonstrates functional domains in the noncoding RNA Xist.

The noncoding RNA Xist has been shown to be essential for X-chromosome inactivation and to coat the inactive X-chromosome (Xi). Thus, an important question in understanding the formation of Xi is whether the binding reaction of Xist is necessary for X-chromosome inactivation. In this article, we demonstrate the failure of X-chromosome silencing if the association of Xist with the X-chromosome is inhibited. The chromatin-binding region was functionally mapped and evaluated by using an approach for studying noncoding RNA function in living cells that we call peptide nucleic acid (PNA) interference mapping. In the reported experiments, a single 19-bp antisense cell-permeating PNA targeted against a particular region of Xist RNA caused the disruption of the Xi. The association of the Xi with macro-histone H2A is also disturbed by PNA interference mapping.

Animals↗

A survey of social services needs assessments for elderly mentally ill people in England and Wales.

OBJECTIVE: to examine variations in the needs assessment policies and practices of social services departments in England and Wales in dealing with elderly people who have mental illness. DESIGN: postal questionnaire survey. SUBJECTS: a random sample of 61 of 119 social services departments in England and Wales. MAIN OUTCOME MEASURE: 99-item questionnaire. RESULTS: 40 responses were received (66%). There were substantial differences in the way referrals were screened before needs assessment and in the design of needs assessment procedures. Disagreements between health and social services were common and, although mechanisms existed to respond to urgent needs, almost one-third found such responses difficult to make. CONCLUSIONS: there are national variations in the way needs assessments are performed by social services, which may lead to inequalities in provision of care to individuals. The lack of a standardized approach impedes comparisons of need between areas which might aid in the distribution of resources at a national level.

Aged↗

Nalmefene enhances LH secretion in a proportion of oligo-amenorrheic athletes.

The influence upon LH secretion of doses of nalmefene, an orally effective congener of naloxone, and a placebo was compared in nine oligo-amenorrheic athletes with that in five regularly menstruating non-athletic women as a test for periodic elevations in hypothalamic opioid tone. After a 360-min control period, LH levels were followed for an additional 360 min following ingestion of the medications in random order approximately six weeks apart, 10-min blood sampling being employed throughout. The mean amplitude post-nalmefene in the athletes was significantly greater than pre (p < 0.05), although there were no differences in the frequency of LH pulses after placebo or nalmefene ingestion. Subjects were labelled as "responders" if their peak AUC after treatment exceeded their pretreatment AUC for LH by more than 1.96 SD (p < 0.05). There were no placebo responders, but 5/9 of the athletes and 1/5 of the menstruating controls were classified as nalmefene responders (p < 0.05). In addition, a variable proportion of the athletes (but none of the controls) experienced symptoms suggestive of narcotic withdrawal 1-4 h after ingesting nalmefene and again 12-18 h later. It appears that demonstrable increases in opioid tone occur at least transiently in a proportion of oligo-amenorrheic athletes.

Adult↗

Methylated ubiquitin inhibits cyclin degradation in clam embryo extracts.

A derivative of ubiquitin in which amino groups were blocked by reductive methylation was used to study the possible role of the ubiquitin pathway in the cell cycle-programmed degradation of cyclin. It was shown previously that methylated ubiquitin can be efficiently ligated to protein substrates, but cannot form polyubiquitin chains. In the well-characterized ubiquitin-dependent proteolytic system from reticulocytes, it was found that rates of protein breakdown obtained with methylated ubiquitin are generally slower than those with ubiquitin; and thus, this derivative can be used, in some cases, as an inhibitor of ubiquitin-dependent protein degradation. The addition of methylated ubiquitin to a cell-free system from fertilized clam oocytes inhibited the degradation of both cyclins A and B. That this was due to specific interference with ubiquitin function was indicated by the observation that the supplementation of excess ubiquitin completely overcame the inhibitory action of methylated ubiquitin on cyclin degradation. These findings suggest that polyubiquitin chain formation is required for cyclin degradation.

Animals↗

The pathology of intrauterine thyrotoxicosis: two case reports.

The autopsy findings are described in two infants of hyperthyroid mothers in whom the clinical symptomatology, laboratory data, and autopsy findings strongly suggested intrauterine thyrotoxicosis secondary to transplacental thyroid-stimulating immunoglobulin. Documented intrauterine thyrotoxicosis is extremely rare, and we believe these to be the first detailed pathologic descriptions of the entity. Autopsy findings included slim habitus, massive thyromegaly, hypertrophic cardiomegaly, congestive visceromegaly, pulmonary hypertension, adenopathy, and prominent amniotic fluid aspiration. Both cases illustrate the positive contribution that a carefully performed autopsy, even in the severely macerated stillborn, can make toward better understanding of intrauterine disease.

Adult↗

Intracellular metabolism of hCG.

After administration of hCG, hormone enters pseudopregnant rat ovarian cells rapidly. Although evidence for small amounts of hCG bound to receptor exists within cells, the major fraction of internalized hCG is free and not receptor bound. The intracellular site of dissociation of hCG from its receptor is unknown. With internalization the hCG molecule is altered so that most of the hormone will no longer bind to concanavalin A. No free hCG alpha or hCG beta was observed for up to 24 hours after internalization. Immunoreactive hCG in cytosol eluted before native highly purified hCG and that altered hCG form may reflect changes in the carbohydrate component of hCG, metabolism of the protein core, or both. Most of the immunoreactive hCG within cytosol remains biologically active for several hours after internalization. The biologic to immunologic (B/I) ratio remained greater than 1.0 for the first six hours after a single injection of hCG. To ascertain whether internalized hCG was predominantly metabolized by lysosomal enzymes in vivo, pseudopregnant rats were pretreated with chloroquine. For the first few hours after hCG stimulation, those animals pretreated with chloroquine attained greater hCG concentrations within the cytosol but membrane bound hCG was lower than that attained for controls. That disparity probably reflected a combination of altered recycling of free hCG receptor in response to chloroquine as well as chloroquine's protecting hormone from lysosomal proteases for a short time after internalization.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Electrocardiographic and hemodynamic effects of tocainide (W-36095) in man.

Tocainide is a new antiarrhythmic drug with a chemical structure related to that of lidocaine. In the present study, healthy volunteers were investigated after infusion of tocainide 450 mg over 45 min. In nine subjects His bundle electrograms, sinus recovery time and ventricular effective refractory periods were recorded. No major changes were seen. In eight cases the hemodynamic effects at rest and during exercise were studied. No significant circulatory effects were observed. No clinically important side-effects were noted.

Adult↗

Effect of acute exercise on plasma neurotensin levels.

Neurotensin (NT) levels were examined in five aerobically untrained females aged 20-36 engaged in acute graded exercise testing. In addition to radioimmunoassay measurements, high pressure liquid chromatography was performed to further characterize plasma NT-like immunoreactivity (NTLI). Epinephrine (E), norepinephrine (NE), and lactate (L) responses were also determined. Exercise testing consisted of one hour of treadmill running subdivided into three 20-minute segments representing 50, 60, and 70%, respectively, of the previously determined maximal aerobic capacity. Mock testing established baseline values for each subject. Three components of NTLI were evaluated: NT(1-13), NT(1-8), and NT(1-11). Resting NT(1-13) concentrations averaged 5.8 +/- 4.2 fmol/ml, while mean NT(1-8) values were 13.0 +/- 5.2 fmol/ml, and NT(1-11) averaged 5.8 +/- 3.2 fmol/ml. Peak exercise values were: for NT(1-13), 5.4 +/- 2.0 fmol/ml, for NT(1-8), 13.5 +/- 2.8 fmol/ml, and for NT(1-11), 5.9 +/- 0.5 fmol/ml. Analysis of variance with repeated measures detected no changes in these levels with exercise. Four-fold increases in E (36 +/- 3 pg/ml to 121 +/- 51 pg/ml), NE (340 +/- 95 pg/ml to 1431 +/- 319 pg/ml), and L (0.8 +/- 0.1 mM to 4.3 +/- 1.7 mM) confirmed the stress of exercise on the body in general, and the sympatho-adrenal system in particular. While other research has associated peripheral NT metabolite elevations with stressful stimuli in laboratory animals, the results of the present study suggest either that NT is not released from the human adrenal medulla during exercise, or that peripheral sampling precludes detection of any increases in NT from the adrenal medulla with currently available radioimmunoassay systems.

Adult↗