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M Johnston

Publications and source records attributed to M Johnston.

At least 181 records · Page 10Linked to original sources
PubMed1993

Do coagulation screening tests detect increased generation of thrombin and plasmin in sick newborn infants?

BACKGROUND: Disseminated intravascular coagulation (DIC) is usually diagnosed in sick infants who have prolonged clotting times, depletion of platelets and coagulation factors, and elevated levels of fibrin derivatives. However, the diagnostic accuracy of abnormal coagulation profiles in neonates at risk of DIC has been uncertain. Since DIC is characterized by activation of both the coagulation and fibrinolytic systems, the objective of this study was to determine whether coagulation screening tests correctly identify infants with biochemical evidence of increased thrombin and plasmin generation. METHODS: Non-surgical patients in a tertiary care nursery who were sick enough to require an indwelling arterial catheter for monitoring purposes, were enrolled in a prospective cohort study. Blood samples for thrombin/antithrombin III (TAT) complexes and the plasmin-derived fibrinopeptide B beta 1-42 were drawn 36 to 72 h after birth from a free-flowing arterial line. Platelet counts, D-Dimer levels, plasma fibrinogen concentrations and prothrombin times, expressed as International Normalized Ratios or INR, were measured at the same time. RESULTS: One hundred patients were studied. Fifty-seven infants had elevated levels of TAT (> or = 4 micrograms/l) and B beta 1-42 (> or = 4 nmol/l). The sensitivities of platelets < 150 x 10(9)/l, D-Dimer > 500 ng/ml, fibrinogen < 1.5 g/l, and INR > 1.5 were 39%, 30%, 12%, and 11%, respectively. Corresponding specificities were 88%, 91%, 98%, and 95%. CONCLUSIONS: Abnormal coagulation screens in sick newborn infants strongly support a diagnosis of DIC. However, normal screens do not exclude activation of the coagulation and fibrinolytic systems.

Antithrombin III↗
PubMed1993

An antithrombin III assay based on factor Xa inhibition provides a more reliable test to identify congenital antithrombin III deficiency than an assay based on thrombin inhibition.

OBJECTIVES: To determine whether functional antithrombin III (AT-III) levels measured by a factor Xa inhibition (AT-III-Xa) assay identifies AT-III deficient individuals more reliably than functional AT-III levels measured by a thrombin inhibition (AT-III-IIa) assay. STUDY DESIGN: Cross-sectional study. PATIENT POPULATION: Sixty-seven members of a large family with type 2 AT-III deficiency. INTERVENTION: DNA analysis was used as the reference diagnostic standard for AT-III status and subjects were classified as AT-III deficient or non deficient according to these results. Functional AT-III levels were measured in all subjects using: 1) a chromogenic substrate for thrombin and added human thrombin (AT-III-IIa), and 2) a chromogenic substrate for factor Xa and added bovine factor Xa (AT-III-Xa). Functional heparin cofactor II (HC-II) levels were measured using a commercially available kit. The proportions of 125I-alpha-thrombin complexed to AT-III and HC-II were measured by polyacrylamide gel electrophoresis and autoradiography. RESULTS: Thirty-one (46%) individuals were classified as AT-III deficient and 36 (54%) as AT-III non deficient. AT-III-Xa assay measured a significantly lower mean AT-III value and a narrower range for individuals classified as AT-III deficient than the AT-III-IIa assay. Using the AT-III-IIa assay, six subjects had borderline AT-III levels compared to none with the AT-III-Xa assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Syntactic processing and written language output in first onset psychosis.

Written language samples from 45 schizophrenic patients were compared with those from 15 manics and 18 non-psychiatrically ill control subjects. We used the Hunt test to generate written language samples. This consists of 32 simple propositions describing the manufacture of Aluminum. Subjects are asked to rewrite the propositions in a more concise style. Analysis of the subjects' responses yields measures of syntactic complexity as well as syntactic and semantic errors. Schizophrenics performed as well as the other groups as far as complexity was concerned. This was quite unexpected, given the substantial evidence from speech studies that schizophrenic utterance is characterized by low syntactic complexity. Both patient groups also made more errors and had difficulty in integrating information successfully, compared with controls. Some of these differences were related to educational differences between the groups, as well as impairments in attention and working memory. A possible mechanism for these relationships is outlined. The results suggest that although working memory and attention have an important bearing on linguistic performance, there is in addition, a specific failure of language processing.

Adolescent↗
PubMed1993

Direct cloning of yeast genes from an ordered set of lambda clones in Saccharomyces cerevisiae by recombination in vivo.

We describe a technique that facilitates the isolation of yeast genes that are difficult to clone. This technique utilizes a plasmid vector that rescues lambda clones as yeast centromere plasmids. The source of these lambda clones is a set of clones whose location in the yeast genome has been determined by L. Riles et al. in 1993. The Escherichia coli-yeast shuttle plasmid carries URA3, ARS4 and CEN6, and contains DNA fragments from the lambda vector that flank the cloned yeast insert. When yeast is cotransformed with linearized plasmid and lambda clone DNA, Ura+ transformants are obtained by a recombination event between the lambda clone and the plasmid vector that generates an autonomously replicating plasmid containing the cloned yeast DNA sequences. Genes whose genetic map positions are known can easily be identified and recovered in this plasmid by testing only those lambda clones that map to the relevant region of the yeast genome for their ability to complement the mutant phenotype. This technique facilitates the isolation of yeast genes that resist cloning either because (1) they are underrepresented in yeast genomic libraries amplified in E. coli, (2) they provide phenotypes that are too marginal to allow selection of the gene by genetic complementation or (3) they provide phenotypes that are laborious to score. We demonstrate the utility of this technique by isolating three genes, GAL83, SSN2 and MAK7, each of which presents one of these problems for cloning.

Bacteriophage lambda↗
PubMed1993

Genetic and molecular characterization of GAL83: its interaction and similarities with other genes involved in glucose repression in Saccharomyces cerevisiae.

Expression of the GAL genes of Saccharomyces cerevisiae is subject to glucose repression, a global regulatory mechanism that requires several gene products. We have isolated GAL83, one of these genes required for glucose repression. The sequence of the predicted Gal83 protein is homologous to two other yeast proteins, Sip1p and Sip2p, which are known to interact with the SNF1 gene product, a protein kinase required for expression of the GAL genes. High-copy clones of SIP1 and SIP2 cross-complement the GAL83-2000 mutation (as well as GAL82-1, a mutation in another gene involved in glucose repression), suggesting that these four genes may perform similar functions in glucose repression. Consistent with this hypothesis, a gal83 null mutation does not affect glucose repression, and only dominant or partially dominant mutations exist in GAL83 (and GAL82). Two other observations were made that suggests that GAL83 functions interdependently with GAL82 and REG1 (another gene involved in glucose repression) to effect glucose repression: 1) REG1 on a low-copy plasmid cross-complements GAL82-1 and GAL83-2000 mutations, and 2) all pairwise combinations of reg1, GAL82-1 and GAL83-2000 fail to complement one another. Such unlinked noncomplementation suggests that Gal83p, Gal82p and Reg1p may interact with one another. Possible roles for GAL83, GAL82 and REG1 are discussed in relation to SNF1, SIP1 and SIP2.

AMP-Activated Protein Kinases↗
PubMed1993

Promoter elements determining weak expression of the GAL4 regulatory gene of Saccharomyces cerevisiae.

The GAL4 gene of Saccharomyces cerevisiae (encoding the activator of transcription of the GAL genes) is poorly expressed and is repressed during growth on glucose. To determine the basis for its weak expression and to identify DNA sequences recognized by proteins that activate transcription of a gene that itself encodes an activator of transcription, we have analyzed GAL4 promoter structure. We show that the GAL4 promoter is about 90-fold weaker than the strong GAL1 promoter and at least 7-fold weaker than the feeble URA3 promoter and that this low level of GAL4 expression is primarily due to a weak promoter. By deletion mapping, the GAL4 promoter can be divided into three functional regions. Two of these regions contain positive elements; a distal region termed the UASGAL4 (upstream activation sequence) contains redundant elements that increase promoter function, and a central region termed the UESGAL4 (upstream essential sequence) is essential for even basal levels of GAL4 expression. The third element, an upstream repression sequence, mediates glucose repression of GAL4 expression and is located between the UES and the transcriptional start site. The UASGAL4 is unusual because it is not interchangable with UAS elements in other yeast promoters; it does not function as a UAS element when inserted in a CYC1 promoter, and a normally strong UAS functions poorly in place of UASGAL4 in the GAL4 promoter. Similarly, the UES element of GAL4 does not function as a TATA element in a test promoter, and consensus TATA elements do not function in place of UES elements in the GAL4 promoter. These results suggest that GAL4 contains a weak TATA-less promoter and that the proteins regulating expression of this regulatory gene may be novel and context specific.

Base Sequence↗
PubMed1993

Coping with motor neurone disease--an analysis using self-regulation theory.

Medicine and environmental changes have had tremendous success in controlling the infectious diseases that were the major causes of death in the last century. However, the consequential extension of life has been accompanied by an increase in the number of persons living with and dying of chronic illness. Despite these changes and their implications, the means by which people cope with such illnesses has only recently begun to receive the attention the subject warrants. Such diseases have a high prevalence in the population and self-detection and self-management are critical to the treatment and control of chronic disease and disability. This paper examines how people cope with motor neurone disease and sets this in the context of earlier research on psychological aspects of chronic disease and current theoretical approaches to coping with long-term ill health.

Adaptation, Psychological↗
PubMed1993

Anxiety, knowledge and satisfaction in women receiving false positive results on routine prenatal screening: a randomized controlled trial.

The majority of women receiving an abnormal result on routine prenatal screening subsequently give birth to unaffected children. Previous studies have documented high levels of anxiety in women receiving such false positive results. In an attempt to reduce this anxiety, two methods of preparing women for undergoing such testing were compared: provision of detailed written information about maternal-serum alpha-fetoprotein testing; and anxiety management training. Eligible women were randomly allocated to one of five groups. Eighty-five women subsequently received false positive results on routine alpha-fetoprotein testing. There was some evidence that completing the study questionnaires had an anxiety-reducing effect. In contrast with the results of previous studies, there was no evidence that receipt of an abnormal alpha-fetoprotein result resulted in raised anxiety. Neither of the interventions, alone or in combination, had an effect upon anxiety following an abnormal alpha-fetoprotein result. Receipt of detailed written information however, led to women having more knowledge and being more satisfied with the amount of information that they had. One in three of the class groups reported that the classes had influenced the way they had dealt with worries. Although the interventions did not reduce anxiety in this study, there are other reasons for considering their incorporation into routine clinical practice.

Anxiety↗
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↗