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Biomedical subjects

M Johnston

Publications and source records attributed to M Johnston.

At least 235 records · Page 13Linked to original sources
PubMed1988

Monitoring beta-lactamase activity in vivo by 13C nuclear magnetic resonance spectroscopy.

A 13C-labeled cephalothin, 7 beta-(2-thienylacetamido)-3-[acetoxy-13C1]methyl-3-cephem-4- carboxylate (compound 1), has been prepared and used to monitor beta-lactamase activities by 13C nuclear magnetic resonance spectroscopy. Time-elapsed spectral analysis of the reaction of the labeled cephalothin with the TEM-2 beta-lactamase purified from Escherichia coli revealed the progressive loss of the cephalothin acetyl resonance at 176.8 ppm and accumulation of an acetate signal at 184.3 ppm. Spectral results identical to those observed in the in vitro experiment were obtained when compound 1 was incubated with cell suspensions of E. coli JSR-O (pBR322), which contains the plasmid-encoded TEM-2 beta-lactamase, and Enterobacter cloacae strains that contain a class I chromosomal beta-lactamase. Pseudo-first-order rate constants for the lactamase-catalyzed formation of acetate from cephalothin in vivo were obtained by integration of the 13C-acetyl resonances of compound 1 during timed incubations with cell preparations. These results constitute the first demonstration of the ability to monitor beta-lactamase activity in viable cells by nuclear magnetic resonance spectroscopy.

Cephalothin↗
PubMed1988

The Foster Care Research Project: summary and analysis.

This paper analyzes and summarizes five more detailed papers describing the Foster Care Research Project (F.C.R.P.). This compared two (individual and group) models of foster care as to their effects on foster parent satisfaction, placement breakdowns and several indices of children's adjustment in care. The group model is described and contrasted with other "extended family" models, and the results of the project, which were mixed, are summarized. A critique of the experimental design suggests why clinical gains noted in the children were not borne out experimentally. Following a clinician's analysis of the process by which the group model operated (illustrated by clinical vignettes), the paper ends by describing the content and process of two support groups for the natural children of the foster parents.

Adaptation, Psychological↗
PubMed1988

Laminar flow air cleaner bed attachment: a controlled trial.

Thirteen house dust mite-allergic young asthmatics were entered into a double-blind, crossover clinical trial to compare "in use" with "non-use" of a laminar flow air cleaner bed attachment. The study design encouraged maintenance of symptom control by adjustment of the dose of medications used. There was a significant reduction in the amount of medications required by the patients during the trial period that the air cleaner was in use. Histamine airway responsiveness was significantly decreased for a group of eight of the subjects tested at the end of a 3-month open trial.

Adolescent↗
PubMed1988

Development of a community health programme.

This formulation of the steps necessary to develop a community health programme is based on Ms Johnston's considerable experience in the "Dana Sehat" programme in Central Java, Indonesia. "Dana Sehat" means health funds and the programme is based on the concept of a community development programme, built upon a health insurance scheme. Further details on the Dana Sehat programme were given in CONTACT 31 "Community Health Care in Rural Java" and in an article by Dr Gunawan Nugroho in the WHO book "Health by the People", 1975. The following outline was first printed in CONTACT 43, February 1976.

Community Health Services↗
PubMed1988

Development of the human coagulation system in the healthy premature infant.

This study was designed to determine the postnatal development of the human coagulation system in the healthy premature infant. Consecutive mothers of healthy premature infants born at either St Joseph's Hospital or McMaster University Medical Centre in Hamilton were asked for consent. One hundred thirty-seven premature infants (30 to 36 weeks of gestational age) entered the study. The premature infants did not have any major health problems and did not require ventilation or supplemental oxygen. Demographic information and a 20-mL blood sample were obtained in the postnatal period on days 1, 5, 30, 90, and 180. Between 40 and 96 premature infants were studied on each day for each of the following tests: prothrombin time, activated partial thromboplastin time, thrombin clotting time, plasminogen; 13 factor assays [fibrinogen, II, V, VII, VIII, IX, X, XI, XII, XIII, high-mol-wt kininogen (HMWK), prekallikrein (PK), von Willebrand factor (vWF)] and eight inhibitors [antithrombin III (AT-III), heparin cofactor II, alpha 2-antiplasmin, alpha 2-macroglobulin, alpha 1-antitrypsin, C1 esterase inhibitor, protein C (PC), and protein S (PS)]. A combination of biologic and immunologic assays were used. Between 30 to 36 weeks there was a minimal effect of gestational age for levels of AT-III, PC, and factors II and X only; therefore, the entire data set was used to generate reference ranges for these components of the coagulation system for premature infants. Next, the results for the premature infants were compared with those of a previously published study in 118 fullterm infants and with those for adults. An effect of gestational age was shown for plasminogen, fibrinogen, factors II, V, VIII, IX, XI, XII, HMWK, and all eight inhibitors. In general, the postnatal maturation towards adult levels was accelerated in premature infants as compared with the fullterm infants. By 6 months of age, most components of the coagulation system in premature infants had achieved near adult values.

Age Factors↗
PubMed1987

Inactivation of alanine racemase by beta-chloro-L-alanine released enzymatically from amino acid and peptide C10-esters of deacetylcephalothin.

The reactions of a set of amino acid and peptidyl C10-esters of deacetylcephalothin (1-5) have been examined with purified enzymes in vitro. Each of the compounds examined is a substrate for the Escherichia coli TEM-2 beta-lactamase, and enzyme-catalyzed hydrolysis of the lactam bond gives release of an amino acid or a peptidyl fragment from a cephem nucleus. 7 beta-(2-Thienylacetamido)-3-[[(beta-chloro-L-alanyl)oxy]methyl]-3- cephem-4-carboxylate (4) gives time-dependent inactivation of E. coli JSR-O alanine racemase in a process that requires beta-lactamase for the initial liberation of beta-chloro-L-alanine from the cephalosporin. Alanine racemase is similarly inactivated by 7 beta-(2-thienylacetamido)-3-[[[(beta-chloro-L-alanyl)-beta-chloro- L- alanyl]oxy]methyl]-3-cephem-4-carboxylate (1), but this inhibition requires the sequential action of both beta-lactamase and alanine aminopeptidase. Analysis of the enzymatic transformations of 7 beta-(2-thienylacetamido)-3-[[[(beta-chloro-L-alanyl)-L- alanyl]oxy]methyl]-3-cephem-4-carboxylate (3), monitored by high-field 1H NMR, reveals that (1) beta-lactamase releases the dipeptide beta-chloro-L-alanyl-L-alanine from 3 and (2) leucine aminopeptidase effects stoichiometric hydrolysis of the dipeptide to beta-chloro-L-alanine and L-alanine. These biochemical findings are discussed with reference to the mechanism of antibacterial action of 1 against beta-lactamase-producing, penicillin-resistant microorganisms [Mobashery, S., Lerner, S. A., & Johnston, M. (1986) J. Am. Chem. Soc. 108, 1685].

Alanine↗
PubMed1987

Recovery from physical disability after stroke: normal patterns as a basis for evaluation.

In 368 patients with residual hemiplegia after stroke, monitoring of recovery over eight weeks showed a distinct time-related pattern. Patterns of this sort could provide useful baselines in various conditions entailing physical disability, allowing comparison of individual scores with the average for that phase of the illness, the setting of precise goals, and the examination of factors that influence recovery.

Cerebrovascular Disorders↗
PubMed1987

Diagnosis of pulmonary nodules in the cancer patient: the role for routine culture and an unusual application of the human tumor colony-forming assay.

Many solid tumors that occur in humans tend to metastasize to the lungs. The etiology of pulmonary nodules in cancer patients, therefore, presents a diagnostic problem that can be resolved only by histologic evaluation or resection. We present two cases of cancer patients with preoperative and intraoperative diagnoses of metastatic lung tumors. Tissue culture using the Human Tumor Colony-Forming Assay (HTCFA), a procedure that predicts chemosensitivity patterns of tumors, was employed to successfully diagnose those nodules as fungal infections. In one case, results using the HTCFA were crucial in the identification of the opportunistic organism. These cases stress the importance of routine culture of all pulmonary nodules and present an unusual but noteworthy application of the HTCFA system.

Adolescent↗
PubMed1987

Goals of treatment in diabetes: a comparison of doctors and parents of children with diabetes.

Treatment failure is usually understood as a problem of patient compliance. This paper suggests another approach: to see this problem as resulting from a difference in the goals of the two parties involved, the doctor and the patient. Comparison was made between the goals of doctors and those of parents in treating children with diabetes. Significant differences emerged between the goals. Parents' goals of treatment were governed more by avoidance of the short-term threat of diabetes (hypoglycemia); doctors' goals more by the long-term threat of diabetes (diabetic complications). The outcome of treatment (diabetic control) was more closely related to parents' than doctors' goals of control. These results indicate that doctors and patients do not always share the same goals in treatment. It is suggested that a more effective clinical alliance would result if the goals of the clinical team were at least made explicit, even if they were not always shared.

Adolescent↗
PubMed1987

Mutations that inactivate a yeast transcriptional regulatory protein cluster in an evolutionarily conserved DNA binding domain.

The protein encoded by the GAL4 gene of the yeast Saccharomyces cerevisiae binds to DNA upstream of several genes and activates transcription. To try to understand these processes, we have undertaken a genetic analysis of GAL4. Here we report that nearly all missense mutations in GAL4, selected in vivo to lack function of the protein, cluster in the small region of the gene that encodes the DNA binding domain. About half of these mutations alters a cysteine-rich region of the protein highly homologous to several eukaryotic DNA binding proteins; the other half alters some of the 20 amino acids adjacent to the cysteine-rich region. Nearly all of the missense mutations that alter the DNA binding domain abolish the DNA binding activity of GAL4 protein measured in vitro. In contrast, nearly all of the mutations that alter the 3' 95% of the gene that encodes the transcription activation function are nonsense or frameshift mutations. These results support the idea that the conserved cysteine-rich sequence motif is directly involved in binding of several eukaryotic transcriptional regulatory proteins to DNA.

Amino Acid Sequence↗
PubMed1987

Prognostic factors for continued or rebleeding and death from gastrointestinal haemorrhage in the elderly.

We analysed 103 episodes of upper gastrointestinal bleeding in 88 elderly patients (age 76 +/- 7.7 years) to determine which of a group of 52 clinical and laboratory variables, measured on admission, best predicted continued or rebleeding, and death in these patients. Variables which related directly to the size of the bleed (blood urea, haemoglobin, pulse rate, systolic blood pressure) were all strongly predictive of both outcomes (P less than 0.001). Of the variables unrelated to the size of the bleed, prolonged prothrombin time and elevated serum creatinine were most strongly predictive of a poor outcome, suggesting that haemostatic dysfunction may be a major contributor to death from upper gastrointestinal haemorrhage in elderly patients. Other variables with strong predictive potential were age (P less than 0.001), the presence of multiple disease states (P less than 0.01), therapy with multiple drugs (P less than 0.01) and acute stroke or obtundation on admission (P less than 0.01). In general terms the size of the bleed was as significant as the premorbid condition of the patient in predicting the outcome. This, together with the fact that half the patients died of hypovolaemia, suggests that death from upper gastrointestinal bleeding in the elderly is not inevitable and that further reduction in mortality from this cause is attainable.

Aged↗
PubMed1987

Cognitive impairment, emotional disorder and length of stay of elderly patients in a district general hospital.

All patients over 65 in a district general teaching hospital (n = 204) were screened for cognitive impairment and emotional disorder using the Clifton Assessment Procedures for the Elderly, the Mini-Mental State and the General Health Questionnaire. Patients scoring in the disordered range were psychiatrically assessed. These procedures gave an estimated prevalence of cognitive impairment of 22 per cent in the 164 patients satisfactorily assessed. Forty-three per cent of patients scored beyond the GHQ cut-off, but there was a high false positive rate. Cognitively impaired patients had a significantly longer hospital stay than the unimpaired. The majority (60 per cent) of these patients could not be discharged because of lack of an appropriate place elsewhere. Amongst all elderly patients whose discharge was prevented in this way, the cognitively impaired were markedly over-represented. The data have implications for the efficient use of hospital beds and for the welfare of elderly patients in acute hospitals.

Affective Symptoms↗
PubMed1987

Development of the human coagulation system in the full-term infant.

The investigation of many hemostatic defects in the newborn is limited by the lack of normal reference values. This study was designed to determine the postnatal development of the human coagulation system in the healthy full-term infant. Consecutive mothers of healthy full-term infants born at St Joseph's Hospital in the city of Hamilton were approached for consent. One hundred eighteen full-term infants (37 to 42 weeks' gestational age) were entered into the study. Demographic information and a 2-mL blood sample were obtained in the postnatal period on days 1, 5, 30, 90, and 180. Between 40 and 79 full-term infants were studied on each day for each of the coagulation tests. Plasma was fractionated and stored at -70 degrees C for batch assaying of the following tests: prothrombin time, activated partial thromboplastin time, thrombin clotting time, and factor assays (biologic): fibrinogen, II, V, VII, VIII, IX, X, XI, XII, and high-molecular weight kininogen. Factor XIII subunits A and S, von Willebrand factor, and the inhibitors antithrombin III, alpha 2-antiplasmin, alpha 2-macroglobulin, alpha 1-antitrypsin, C1 esterase inhibitor, protein C, and protein S were measured immunologically. Plasminogen, prekallikrein, and heparin cofactor II were measured by using chromogenic substrates. The large number of infants studied at each time point allowed us to determine the following: the range of normal for each test at five time points in the postnatal period; that coagulation tests vary with the postnatal age of the infant; that different coagulation factors show different postnatal patterns of maturation; and that near-adult values are achieved for most components by 6 months of life. In summary, this large cohort of infants studied consecutively in the postnatal period allowed us to determine the normal development of the human coagulation system in the full-term infant.

Aging↗
PubMed1987

Metabolic and hormonal effects of 25-mg and 50-mg 17 beta-estradiol implants in surgically menopausal women.

A prospective study involving 12 surgically menopausal women was undertaken to determine whether 17 beta-estradiol pellets could maintain bone mineral content without inducing adverse cardiovascular side effects. Surgically menopausal women were randomly selected to have either 25-mg or 50-mg pellets implanted subcutaneously. The bone mineral content of the midshaft of the nondominant radius in the combined group--measured by single photon absorptiometry--increased by 1.8% over the two-year period of observation (P less than .03); the distal bone mineral content of the radius was maintained at 0.8% per annum. No adverse effects were noted in the coagulation profiles or in the coagulation inhibition and fibrinolysis assays of both groups. Serum high-density lipoprotein cholesterol and triglycerides were unaltered, but serum cholesterol values decreased during the six-month period of observation by 14 mg/dL (P less than .05) and 11 mg/dL in the 25- and 50-mg groups, respectively. Carbohydrate and insulin metabolism was unaffected, as was the systolic and diastolic blood pressure. There were no significant intergroup differences in any of the parameters measured. The serum estradiol/estrone ratios of 1.45 and 1.59 reflected a physiologic estrogen milieu at the 25- and 50-mg dosages. Subcutaneous 17 beta-estradiol pellets can effectively maintain the bone mineral content of surgically menopausal women without inducing adverse cardiovascular side effects.

Adult↗