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Biomedical subjects

M Johnston

Publications and source records attributed to M Johnston.

At least 199 records · Page 11Linked to original sources
PubMed1992

The impact of a death on fellow hospice patients.

The study was designed to examine the impact of a patient's death on other patients in a hospice. Following pilot work, 11 patients who had shared a room with a patient who had died were compared with nine who had been in the hospice for a similar amount of time, but had not witnessed the death of another patient. Those who had witnessed a death were significantly less depressed on a standard measure of emotional distress (the HAD). They also rated the death of another patient as significantly more comforting than distressing. Thus the results point to the benefits rather than disadvantages for patients of witnessing the death of another patient in the hospice.

Adaptation, Psychological↗
PubMed1992

Coagulation screening tests in high risk neonates: a prospective cohort study.

Forty seven infants in a prospective cohort of 170 high risk neonates without signs of overt bleeding had abnormal coagulation screening tests within 36 hours of birth. Early thrombocytopenia was a better predictor of prolonged prothrombin times and hypofibrinogenemia than very low birth weight, fetal growth retardation, or poor five minute Apgar scores.

Blood Coagulation Disorders↗
PubMed1992

Thrombin/antithrombin III complex formation in the neonatal respiratory distress syndrome.

Intravascular and intra-alveolar thrombin generation may exacerbate the pulmonary hypertension and surfactant dysfunction that characterize the neonatal respiratory distress syndrome (RDS). Although low levels of the most important thrombin inhibitor, antithrombin III (AT III), have been reported in infants with RDS, direct evidence of increased intravascular thrombin generation has been lacking. Accordingly, the objective of this study was to determine whether thrombin generation is increased in severe neonatal RDS. Thirty-nine infants of 25 to 29 wk gestation with a clinical and radiologic diagnosis of RDS were enrolled in a prospective cohort study. Plasma levels of thrombin/antithrombin III complexes (TAT) and AT III activity, measured 36 to 72 h after birth, were related to RDS severity. Seventeen infants had severe RDS (mean airway pressure greater than 10 cm H2O or FlO2 greater than 0.8), and 22 had mild or moderate disease. Mean birthweight (1,017 versus 1,054 g) and mean gestational age (27.8 versus 27.4 wk) were similar in both groups. The median TAT level in infants with severe RDS was significantly higher than that in patients with mild or moderate disease (10.7 and 4.0 micrograms/L, respectively; p less than 0.001). In addition, the mean AT III activity in infants with severe RDS was significantly lower than that in less severely affected patients (0.31 and 0.46 U/ml, respectively; p less than 0.01). Considering the entire cohort, plasma TAT levels were inversely correlated with the arterial/alveolar oxygen tension ratio (r = -0.48, p = 0.0022) and the ventilator efficiency index (r = -0.51, p = 0.0011). The elevated TAT levels and reduced AT III activity in infants with severe RDS are consistent with increased thrombin generation and resulting AT III consumption. Therefore, to regulate thrombin activity, these infants may benefit from replacement therapy with AT III concentrate.

Antithrombin III↗
PubMed1992

Factors influencing accuracy of estimation of comprehension problems in patients following cerebrovascular accident, by doctors, nurses and relatives.

Previous work has shown that doctors, nurses and relatives are inaccurate at estimating the comprehension problem of stroke patients. Possible factors that influence the accuracy of these judgements were studied, including confidence of the respondents, the severity of the comprehension problems of the patients and factors specific to relatives (educational background and the length of the relative's relationship with the patient). Doctors, nurses and relatives involved with 30 recently aphasic stroke patients were asked to estimate how patients would perform on the comprehension sections of two tests (Western Aphasia Battery and Functional Communication Profile). Results show that although all respondents over-estimated patients' comprehension abilities, they were more accurate for patients who had mild problems. Doctors and nurses who were more confident about their predictions tended to be more accurate on some parts of the tests than those with less confidence, whereas relatives were equally inaccurate when giving high and low confidence judgements. Length of relationship and educational level did not predict relative's accuracy.

Aged↗
PubMed1991

The relationship of antiphospholipid antibodies to thromboembolic disease in systemic lupus erythematosus: a cross-sectional study.

In order to determine whether an association exists between antiphospholipid antibodies (APLA) and thromboembolic events in patients with systemic lupus erythematosus (SLE), we performed a cross-sectional study of consecutive unselected SLE patients. The occurrence of previous thromboembolic events was determined by investigators blinded to the APLA status of the patients by critical review of objective tests that had been performed at the time of symptomatic presentation and by performing venous Doppler ultrasound of the legs to elicit venous reflux as an indication of previous venous thrombosis. The presence of APLA was determined by coagulation assays for the lupus anticoagulant (LA) using five tests with well-defined control ranges and by ELISA assay for anticardiolipin antibodies (ACLA). These tests were measured on two separate occasions. The results of the study demonstrate a statistically significant association between persistently abnormal ACLA assays and thromboembolic events and a non-significant trend between persistently abnormal LA and thromboembolic events. Transient abnormalities of LA and ACLA were less strongly associated with thromboembolic events. We conclude that in patients with SLE, there is a significant association between thromboembolism and APLA.

Autoantibodies↗
PubMed1991

Regulated expression of the GAL4 activator gene in yeast provides a sensitive genetic switch for glucose repression.

Glucose (catabolite) repression is mediated by multiple mechanisms that combine to regulate transcription of the GAL genes over at least a thousandfold range. We have determined that this is due predominantly to modest glucose repression (4- to 7-fold) of expression of GAL4, the gene encoding the transcriptional activator of the GAL genes. GAL4 regulation is affected by mutations in several genes previously implicated in the glucose repression pathway; it is not dependent on GAL4 or GAL80 protein function. GAL4 promoter sequences that mediate glucose repression were found to lie downstream of positively acting elements that may be "TATA boxes." Two nearly identical sequences (10/12 base pairs) in this region that may be binding sites for the MIG1 protein were identified as functional glucose-control elements. A 4-base-pair insertion in one of these sites causes constitutive GAL4 synthesis and leads to substantial relief (50-fold) of glucose repression of GAL1 expression. Furthermore, promoter deletions that modestly reduce GAL4 expression, and therefore presumably the amount of GAL4 protein synthesized, cause much greater reductions in GAL1 expression. These results suggest that GAL4 works synergistically to activate GAL1 expression. Thus, glucose repression of GAL1 expression is due largely to a relatively small reduction of GAL4 protein levels caused by reduced GAL4 transcription. This illustrates how modest regulation of a weakly expressed regulatory gene can act as a sensitive genetic switch to produce greatly amplified responses to environmental changes.

Base Sequence↗
PubMed1991

Identification of the DNA binding site for NGFI-B by genetic selection in yeast.

An in vivo selection system for isolating targets of DNA binding proteins in yeast was developed and used to identify the DNA binding site for the NGFI-B protein, a member of the steroid-thyroid hormone receptor superfamily. The feasibility of the technique was verified by selecting DNA fragments that contained binding sites for GCN4, a well-characterized yeast transcriptional activator. The DNA binding domain of NGFI-B, expressed as part of a LexA-NGFI-B-GAL4 chimeric activator, was then used to isolate a rat genomic DNA fragment that contained an NGFI-B binding site. The NGFI-B response element (NBRE) is similar to but functionally distinct from elements recognized by the estrogen and thyroid hormone receptors and the hormone receptor-like proteins COUP-TF, CF1, and H-2RIIBP. Cotransfection experiments in mammalian cells demonstrated that NGFI-B can activate transcription from the NBRE with or without its putative ligand binding domain.

Animals↗
PubMed1991

Perceived risk not actual risk predicts uptake of amniocentesis.

A consecutive cohort of 71 women eligible for amniocentesis because they were over 38 years of age completed questionnaires during the first trimester of pregnancy. Sixty-one women underwent amniocentesis, an uptake rate of 86%. Uptake was associated with a less negative attitude towards termination of an affected baby and a higher perceived risk of the fetus being abnormal. It was not associated with actual age-related risks. There was no significant relation between actual risk and perceived risk. The results of this study suggests that it is important for doctors to understand the basis of women's decisions to have amniocentesis, and the difference between actual and perceived risk if they are to communicate effectively with women about the test and their options.

Abortion, Therapeutic↗
PubMed1991

GRR1 of Saccharomyces cerevisiae is required for glucose repression and encodes a protein with leucine-rich repeats.

Growth of the yeast Saccharomyces cerevisiae on glucose leads to repression of transcription of many genes required for alternative carbohydrate metabolism. The GRR1 gene appears to be of central importance to the glucose repression mechanism, because mutations in GRR1 result in a pleiotropic loss of glucose repression (R. Bailey and A. Woodword, Mol. Gen. Genet. 193:507-512, 1984). We have isolated the GRR1 gene and determined that null mutants are viable and display a number of growth defects in addition to the loss of glucose repression. Surprisingly, grr1 mutations convert SUC2, normally a glucose-repressed gene, into a glucose-induced gene. GRR1 encodes a protein of 1,151 amino acids that is expressed constitutively at low levels in yeast cells. GRR1 protein contains 12 tandem repeats of a sequence similar to leucine-rich motifs found in other proteins that may mediate protein-protein interactions. Indeed, cell fractionation studies are consistent with this view, suggesting that GRR1 protein is tightly associated with a particulate protein fraction in yeast extracts. The combined genetic and molecular data are consistent with the idea that GRR1 protein is a primary response element in the glucose repression pathway and is required for the generation or interpretation of the signal that induces glucose repression.

Amino Acid Sequence↗
PubMed1990

Isolation and characterization of the ZWF1 gene of Saccharomyces cerevisiae, encoding glucose-6-phosphate dehydrogenase.

Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the first step of the pentose phosphate pathway, a reaction that generates NADPH. We have isolated ZWF1, the Saccharomyces cerevisiae gene that encodes G6PD, and identified its transcript and transcription start point. Expression of ZWF1 appears not to be regulated, consistent with its 'housekeeping' role. Null mutants lacking G6PD appear to grow normally, but are more sensitive than wild type to oxidizing agents that presumably reduce the level of NADPH. This suggests that G6PD has a major role in NADPH production in yeast. Regulation of GAL1 expression appears normal in zwf1 mutants, suggesting that the pentose phosphate pathway is not involved in glucose repression. The predicted amino acid sequence of yeast G6PD is highly similar to the sequence of the Drosophila, human, and rat enzymes, except near its N terminus, where the yeast and Drosophila sequences diverge from that of human and rat.

Amino Acid Sequence↗
PubMed1990

Development of the hemostatic system in the neonate and young infant.

Our understanding of the coagulation and fibrinolytic systems (the hemostatic system) in the adult has progressed rapidly in recent years. However, a more complete understanding of the physiology of the hemostatic system in the neonate has lagged behind that of the adult for many reasons. First, the hemostatic system in the newborn exists in a dynamic state and is rapidly evolving toward the adult system. This situation necessitates the generation of not one, but several, reference ranges (or ranges of normal values) in the postnatal period for the various tests and components of the hemostatic system. Also, microtechniques must be used to perform the required assays, both because of the small size of blood samples available and because of the difficulty of obtaining blood from infants. Recently, many of these problems have been resolved, which resulted in a better appreciation of the development of the hemostatic system in the infant. This article reviews our current understanding of the protein components of the coagulation and fibrinolytic systems in the neonate. Reference ranges for normal values of the various tests and components of the hemostatic system have been provided for the premature and full-term infant at birth and during the first 6 months of life.

Aging↗
PubMed1990

Phosphorylated forms of GAL4 are correlated with ability to activate transcription.

GAL4I, GAL4II, and GAL4III are three forms of the yeast transcriptional activator protein that are readily distinguished on the basis of electrophoretic mobility during sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Phosphorylation accounts for the reduced mobility of the slowest-migrating form, GAL4III, which is found to be closely associated with high-level GAL/MEL gene expression (L. Mylin, P. Bhat, and J. Hopper, Genes Dev. 3:1157-1165, 1989). Here we show that GAL4II, like GAL4III, can be converted to GAL4I by phosphatase treatment, suggesting that in vivo GAL4II is derived from GAL4I by phosphorylation. We found that cells which overproduced GAL4 under conditions in which it drove moderate to low levels of GAL/MEL gene expression showed only forms GAL4I and GAL4II. To distinguish which forms of GAL4 (GAL4I, GAL4II, or both) might be responsible for transcription activation in the absence of GAL4III, we performed immunoblot analysis on UASgal-binding-competent GAL4 proteins from four gal4 missense mutants selected for their inability to activate transcription (M. Johnston and J. Dover, Proc. Natl. Acad. Sci. USA 84:2401-2405, 1987; Genetics 120;63-74, 1988). The three mutants with no detectable GAL1 expression did not appear to form GAL4II or GAL4III, but revertants in which GAL4-dependent transcription was restored did display GAL4II- or GAL4III-like electrophoretic species. Detection of GAL4II in a UASgal-binding mutant suggests that neither UASgal binding nor GAL/MEL gene activation is required for the formation of GAL4II. Overall, our results imply that GAL4I may be inactive in transcriptional activation, whereas GAL4II appears to be active. In light of this work, we hypothesize that phosphorylation of GAL4I makes it competent to activate transcription.

Alleles↗
PubMed1990

Two systems of glucose repression of the GAL1 promoter in Saccharomyces cerevisiae.

Expression of the GAL1 gene in Saccharomyces cerevisiae is strongly repressed by growth on glucose. We show that two sites within the GAL1 promoter mediate glucose repression. First, glucose inhibits transcription activation by GAL4 protein through UASG. Second, a promoter element, termed URSG, confers glucose repression independently of GAL4. We have localized the URSG sequences responsible for glucose repression to an 87-base-pair fragment located between UASG and the TATA box. Promoters deleted for small (20-base-pair) segments that span this sequence are still subject to glucose repression, suggesting that there are multiple sequences within this region that confer repression. Extended deletions across this region confirm that it contains at least two and possibly three URSG elements. To identify the gene products that confer repression upon UASG and URSG, we have analyzed glucose repression mutants and found that the GAL83, REG1, GRR1, and SSN6 genes are required for repression mediated by both UASG and URSG. In contrast, GAL82 and HXK2 are required only for UASG repression. A mutation designated urr1-1 (URSG repression resistant) was identified that specifically relieves URSG repression without affecting UASG repression. In addition, we observed that the SNF1-encoded protein kinase is essential for derepression of both UASG and URSG. We propose that repression of UASG and URSG is mediated by two independent pathways that respond to a common signal generated by growth on glucose.

Base Sequence↗