Search PubMed⌕ Search

Biomedical subjects

M Johnston

Publications and source records attributed to M Johnston.

At least 19 recordsLinked to original sources
PubMed1992

Maturation of the hemostatic system during childhood.

The hemostatic system is assumed to be similar in children and adults and reference ranges established for adults are commonly used to evaluate children suspected of having congenital or acquired hemostatic problems. However, we know that the hemostatic system is not fully mature by 6 months of age and comprehensive studies of healthy older children have not been published. Therefore, we conducted a prospective cohort study of the hemostatic system in healthy children having minor, elective day surgery. After obtaining informed consent, a 3-mL blood sample was obtained at the time routine preoperative blood work was drawn. The plasma was fractioned and stored at -70 degrees C for batch assaying. We measured the concentration of 33 components of the hemostatic system (functional and immunologic assays) and the bleeding time (automated pediatric device) in 246 children aged 1 to 16 inclusive (a minimum of four subjects at each age). Eleven components of hemostasis (fibrinogen, prekallikrein, high-molecular weight kininogen, factors VIII and XIII, antithrombin III [ATIII], heparin cofactor II [HCII], alpha 1-antitrypsin [alpha 1AT], protein S, plasminogen, alpha 2-antiplasmin [alpha 2AP]) had mean values and ranges of normal that were similar to adults. Mean values of seven coagulants (II, V, VII, IX, X, XI, XII) were significantly lower than adult values and varied with age. Values for three inhibitors, alpha 2-macroglobulin (alpha 2M), protein C, and protein C1-inhibitor (C1-Inh) also differed from adults. Alpha 2M and C1-Inh inhibitor levels were elevated throughout childhood, whereas protein C levels were low, with a lower limit of normal of 0.40 U/mL until the age of 11. Finally, the upper limit of normal for the bleeding time was longer in children during the first 10 years of life, but decreased to adult values in the teenage years. In summary, there are important physiologic differences in the hemostatic system in children compared with adults. The decreased levels of several critical coagulants and increased levels of alpha 2M may contribute in part to the lower risk of thrombotic events in childhood. Age-matched controls should be used for evaluation of the hemostatic system in children with suspected congenital or acquired defects.

Adolescent↗
PubMed1992

Relationship of antiphospholipid antibodies to pregnancy loss in patients with systemic lupus erythematosus: a cross-sectional study.

To determine whether an association exists between the presence of antiphospholipid antibodies and pregnancy loss, a cross-sectional study was performed. Consecutive women who were referred to three outpatient rheumatology clinics and who had systemic lupus erythematosus (SLE) and a history of one or more pregnancies were evaluated. Patients were interviewed to determine outcomes of all previous pregnancies. Blood was taken on two separate occasions at least 3 months apart to test for the presence of the lupus anticoagulant and anticardiolipin antibodies; on both occasions, five tests of the lupus anticoagulant, with well-defined normal ranges, and an enzyme-linked immunosorbent assay to measure IgG anticardiolipin antibodies were performed. Patients were considered to be positive for the lupus anticoagulant if one or more tests was abnormal on both occasions and positive for anticardiolipin antibodies if the test was abnormal on both occasions. Forty-two women were studied. Statistically significant associations were shown between lupus anticoagulant positivity and previous pregnancy loss (odds ratio [OR], 4.8; 95% confidence intervals [CI], 1.0 to 23.6; P = .05) and between anticardiolipin antibody positivity and previous pregnancy loss (OR, 20.0; 95% CI, 1.3 to 97.0; P = .01). All seven women with multiple episodes of pregnancy loss were lupus anticoagulant positive and four of these were also anticardiolipin antibody positive. If patients who are transiently positive for lupus anticoagulant and/or anticardiolipin antibodies are considered to be test positive, the associations with pregnancy loss are no longer statistically significant. Within the group of lupus anticoagulant-positive patients, we observed stronger associations between the presence of six or more positive tests and pregnancy loss than between the presence of two to five positive tests and pregnancy loss. No single test for the lupus anticoagulant provides a statistically significant association with pregnancy loss. The results of our study show that by performing multiple lupus anticoagulant tests and by repeating testing for lupus anticoagulant and anticardiolipin antibodies on more than one occasion, significant associations between the presence of antiphospholipid antibodies and previous pregnancy loss can be shown in patients with SLE.

Abortion, Spontaneous↗
PubMed1992

D-dimer and thrombin-antithrombin III complexes in patients with clinically suspected pulmonary embolism.

One hundred and fifty-six consecutive patients with clinically suspected pulmonary embolism (PE) had blood drawn to measure levels of D-dimer and thrombin-antithrombin (TAT) complexes and underwent ventilation/perfusion (V/Q) lung scanning and bilateral impedance plethysmography (IPG); pulmonary angiography was performed in 10 patients. Patients were classified as: PE-positive (positive pulmonary angiography or high probability lung scan or non-high probability lung scan and abnormal IPG) or, PE-negative (normal lung scan or normal pulmonary angiography) or PE-unlikely (non-high probability lung scan and normal serial IPG and absence of venous thromboembolism in follow-up). Thirty patients were classified as PE-positive, 64 as PE-negative and 62 patients as PE-unlikely. PE-positive patients were treated with anticoagulants, whereas PE-negative and PE-unlikely patients were not. PE-unlikely patients were followed for 3 months with repeat IPG and clinical evaluation for the occurrence of venous thromboembolism. The sensitivities, specificities, positive predictive values and negative predictive values of the D-dimer and TAT complex assays were calculated for patients classified as PE-positive and PE-negative. In addition, the prevalences of normal D-dimer and TAT complex assays were calculated for PE-unlikely patients. Cutoffs of 300 ng/ml for D-dimer and 3.5 micrograms/ml for TAT complexes provided sensitivities of 96% for both assays, negative predictive values of 97% for D-dimer and 96% for TAT complexes and specificities of 52% for D-dimer and 51% for TAT complexes. The specificities of the assays were higher in patients without comorbid conditions and in outpatients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

In vivo mutational analysis of the NGFI-A zinc fingers.

NGFI-A is a mammalian transcription factor that contains zinc fingers similar to those observed in several other proteins, including NGFI-C and Krox-20. To define precisely the DNA binding domain of NGFI-A, we selected mutants using a chimeric transcriptional activator that contains the NGFI-A zinc finger domain sandwiched between the lexA DNA binding domain and the GAL4 transcriptional activating domain. Expression of this lexA-NGFI-A-GAL4 (LAG) trimeric protein in yeast significantly retarded their growth, unlike an activator containing only the lexA and GAL4 components. This suggested that LAG inappropriately regulates genes in yeast that contain NGFI-A binding sites. Yeast that contained LAG reverted to wild-type growth at high frequency by inactivation of LAG. The mutations recovered from these revertants were specifically limited to the 83-residue NGFI-A zinc finger domain by requiring that the lexA and GAL4 portions of the LAG chimera remain functional. Nearly all of the 93 mutants obtained contained single missense mutations that mapped within the zinc fingers to residues thought to be important for zinc finger function. Deletion analysis of native NGFI-A verified that residues distant from the zinc fingers do not influence DNA binding, thus establishing the minimal functional DNA binding domain. Interestingly, many zinc finger residues ascribed specific functions by x-ray crystallography were never mutated in yeast, implying that the identity of these residues is not critical. Surprisingly, not all of the mutations tested significantly impaired NGFI-A-specific DNA binding, suggesting that the function of these zinc fingers is more diverse than previously recognized.

Amino Acid Sequence↗
PubMed1992

The psychological effects of false-positive results in prenatal screening for fetal abnormality: a prospective study.

The purpose of the study was to describe the impact of false-positive results from initial maternal serum alpha-fetoprotein (MS-AFP) screening. The analyses compared two groups of women, those receiving a negative result (n = 346) and those receiving an initial positive result (n = 26), over four time points--prior to testing, immediately after testing, later in pregnancy, and in the post-partum period. Receiving an abnormal result was associated with high levels of anxiety which were reflected in increased worry about the baby's health and a more negative attitude towards the pregnancy and the baby. Women who had an initial abnormal result were offered a variety of further tests. Those women who went on to have amniocentesis were less worried about their baby's health in the third trimester and also less anxious post-partum than those who did not have amniocentesis. In view of the increasing number of screening tests available, it is necessary to establish whether and how these levels of distress can best be reduced.

Adult↗
PubMed1992

Psychological effects of having amniocentesis: are these due to the procedure, the risk or the behaviour?

The purpose of the study was to examine the impact of amniocentesis on women at risk for having a baby with Down's syndrome because of raised maternal age. Fifty-four of the study participants had amniocentesis and nine did not. At the time of the procedure, those having amniocentesis were significantly more anxious, less certain about the baby's health, and held more negative attitudes towards the baby than women who did not undergo amniocentesis. For women undergoing amniocentesis there was a positive association between perceived risk of having an abnormal baby and anxiety. After the baby's birth, women who had undergone amniocentesis held less positive attitudes to the baby and were significantly more worried about the baby's health. These results suggest that the anxiety surrounding amniocentesis is related both to the procedure and to the perceived likelihood of an abnormal result. The differences between the groups after the birth seem more likely to reflect pre-existing attitudinal differences between the two groups, than the effects of amniocentesis.

Adaptation, Psychological↗
PubMed1992

Self-repair in dialogues of schizophrenics: effects of hallucinations and negative symptoms.

This paper concerns the discourse features of verbal hallucinations and negative symptoms of schizophrenia. A total of 46 schizophrenics, varying in verbal hallucination and in negative symptoms status, and 22 controls were tested on the Reporter Test. The frequency with which they issued inadequate instructions, attempted to repair the inadequacies, and the success of repairs were compared. We observed that schizophrenics, on the whole, issued more wrong and incomplete instructions. This was in part related to their worse working memory, but it was not affected by verbal hallucinations or negative symptoms. We observed, further, that schizophrenics had no particular problems monitoring messages for inadequacies. We did find, however, that schizophrenics with verbal hallucinations had a specific problem with self-repairing wrong instructions. We interpret these results in the framework of Hoffman's (1986b) plan disruption-based model of verbal hallucinations; the Frith (1987) and Frith and Done (1988) internal monitoring model of positive and negative symptoms; and finally Frith and Frith's (1990) model of negative and positive schizophrenia and we use the results to specify the models.

Adult↗
PubMed1992

Analysis of URSG-mediated glucose repression of the GAL1 promoter of Saccharomyces cerevisiae.

Repression of GAL1 expression during growth on glucose is mediated in part by cis-acting promoter elements designated URSG. We show that oligonucleotides containing sequences from two regions of URSG confer glucose repression upon a heterologous promoter. Repression caused by URSG is dependent on trans-acting factors of the glucose repression pathway and is independent of orientation or location within a promoter, suggesting that URSG contains binding sites for a glucose-activated repressor protein(s). Genetic analysis identified three apparently novel genes (URR1, URR3 and URR4) that are specifically required for URSG-mediated repression and may encode such repressor proteins. Mutations in the URR genes suppress the defect in URSG derepression caused by a snf1 mutation.

Base Sequence↗
PubMed1992

Changing perceived control in patients with physical disabilities: an intervention study with patients receiving rehabilitation.

Physiotherapy patients' perceptions of personal control over recovery (during rehabilitation) have been shown to be predictive of their progress. An experimental letter, consisting of the routine appointment letter plus some paragraphs designed to increase perceived control, was sent to 39 randomly selected patients prior to their first appointment. The remaining 32 control patients received the routine letter only. Approximately one week after each patient's first appointment, all patients were interviewed. The group to whom the experimental letter had been sent were found, on average, to have significantly higher levels of perceived control and tended to be more satisfied with information than the control group. There were no significant differences between groups on accuracy of expectations of physiotherapy. It is suggested that this type of communication given prior to treatment might lead to patients making better and faster progress with recovery. However, this possibility needs to be investigated by further study.

Persons with Disabilities↗
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↗