Repeat unit multipriming and hybridisation--a novel method for the production of DNA fingerprints using minisatellite probes.
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DNA↗
Biomedical subjects
H Smith
Publications and source records attributed to H Smith.
Early prevention of left ventricular dysfunction after myocardial infarction with angiotensin-converting-enzyme inhibition.
Left ventricular dysfunction can be improved with angiotensin-converting-enzyme inhibition started 1 week after myocardial infarction or later. To see whether earlier intervention may confer greater benefit, a double-blind study was carried out in which 100 patients with Q wave myocardial infarction, but without clinical heart failure, were randomly allocated treatment with captopril 50 mg twice daily or placebo starting 24-48 h after onset of symptoms. Left ventricular volumes were measured regularly during 3 months of treatment and after a 48 h withdrawal period by means of two-dimensional echocardiography. The placebo group showed significant increases in left ventricular end-diastolic (LVEDVI) and end-systolic (LVESVI) volume indices, with the ejection fraction unchanged. By contrast, the captopril group showed a slight but not significant rise in LVEDVI and a significant reduction in LVESVI with ejection fraction increased significantly. At 3 months there was a 4.6% difference in the change in ejection fraction from baseline between the groups (p less than 0.0001). Most of the treatment benefit was evident at 1 month and there were no changes in left ventricular volumes after 48 h withdrawal of treatment at 3 months. Heart failure requiring treatment with frusemide developed in 7 patients in each group during the study period; 3 of these (1 captopril-treated, 2 placebo-treated) had to be withdrawn from the trial with severe heart failure requiring open treatment. Thus early treatment with captopril is effective in preventing the ventricular dilatation that can occur after Q wave myocardial infarction.
Angiotensin-Converting Enzyme Inhibitors↗
Caring for quality.
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Community Health Services↗
Symptomatic reactivation of hepatitis B in pregnancy.
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Adult↗
In vivo measurement of breast cancer growth rate.
S-phase cells of 66 primary breast cancers were labeled in vivo by preoperative infusion of the thymidine analogue bromodeoxyuridine. A monoclonal antibody specific for DNA-incorporated bromodeoxyuridine was used to identify positive cells and compute a labeling index on histologic sections. The labeling index (the percentage of cells in S-phase) ranged from 0.1% to 23.9%; it correlated positively with poorly differentiated cancer, higher mitotic counts on routine histologic examination, and tumor size; and it correlated inversely with estrogen and progesterone receptors. The labeling index did not correlate with nodal involvement or ploidy. Of the 15 patients with a labeling index greater than 12%, three died and one had systemic disease after a median follow-up of 19 months. No other patients had recurrences. There were no clinical complications of bromodeoxyuridine infusion.
Breast Neoplasms↗
Signal peptidase I overproduction results in increased efficiencies of export and maturation of hybrid secretory proteins in Escherichia coli.
The effects of 25-fold overproduction of Escherichia coli signal peptidase I (SPase I) on the processing kinetics of various (hybrid) secretory proteins, comprising fusions between signal sequence functions selected from the Bacillus subtilis chromosome and the mature part of TEM-beta-lactamase, were studied in E. coli. One precursor (pre[A2d]-beta-lactamase) showed an enhanced processing rate, and consequently, a highly improved release of the mature enzyme into the periplasm. A minor fraction of a second hybrid precursor (pre[A13i]-beta-lactamase), which was not processed under standard conditions of SPase I synthesis, was shown to be processed under conditions of SPase I overproduction. However, this did not result in efficient release of the mature beta-lactamase into the periplasm. In contrast, the processing rates of wild-type pre-beta-lactamase and pre(A2)-beta-lactamase, already high under standard conditions, were not detectably altered by SPase I overproduction. These results demonstrate that the availability of SPase I can be a limiting factor in protein export in E. coli, in particular with respect to (hybrid) precursor proteins showing low (SPase I) processing efficiencies.
Bacillus subtilis↗
Plasmodium falciparum: the effect of pH and Ca2+ concentration on the in vitro cytoadherence of infected erythrocytes to amelanotic melanoma cells.
Cytoadherence of Plasmodium falciparum-infected erythrocytes to amelanotic melanoma cells was pH dependent; increased adherence was observed in the pH range of 6.1 to 6.8 and was greatest between pH 6.6 and 6.8 Ca2+ promoted cytoadherence, but at higher concentrations (40-50 mM) than is usually the case for cell-cell adhesion. The effects of pH and Ca2+ were interdependent--the pH optimum of cytoadherence was altered by the Ca2+ concentration in the medium. The adherent properties of several P. falciparum lines (including a knobless cytoadherent line) under varying pH and Ca2+ concentrations were similar.
Animals↗
Infection in hospital: a proposal.
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Cross Infection↗
Prognostic significance of pre-S2 antigen and antibody in fulminant hepatitis B. Evidence for heterogeneous serological responses.
Serial sera were collected prospectively and from early on in the clinical course of ten patients with fulminant hepatitis B. These were analysed for HBV DNA (dot-blot technique), HBsAg, HBeAg, pre-S2-Ag and their respective antibodies. Two patterns emerged in nine of the patients. The first and well-recognised pattern of rapid clearance of antigens and appearance of antibodies was seen in four patients, all of whom survived. The second pattern seen in five patients was one of persistence of HBsAg and pre-S2 antigen and failure to detect antibodies but only one patient survived. The first pattern may reflect a more rapid cessation of virus replication and this may favour liver cell regeneration and recovery. In contrast, the second pattern may indicate continuing virus replication and liver cell damage which could contribute to the high mortality in some patients with fulminant hepatitis B.
Adolescent↗
MULTI: a shared memory approach to cooperative molecular modeling.
A general purpose molecular modeling system, MULTI, based on the UNIX shared memory and semaphore facilities for interprocess communication is described. In addition to the normal querying or monitoring of geometric data, MULTI also provides processes for manipulating conformations, and for displaying peptide or nucleic acid ribbons, Connolly surfaces, close nonbonded contacts, crystal-symmetry related images, least-squares superpositions, and so forth. This paper outlines the basic techniques used in MULTI to ensure cooperation among these specialized processes, and then describes how they can work together to provide a flexible modeling environment.
Computer Communication Networks↗
A new device to stabilize templates for transperineal I-125 implants.
Transperineal Iodine-125 implants of the prostate are currently being performed at Memorial Sloan-Kettering Cancer Center with CT-based treatment planning and transrectal ultrasound for verification of proper needle placement in the prostate at the time of implantation. An adjustable device, the WIPI, has been designed to stabilize the perineal template and rectal obturator during planning and implementation of the procedure. The device is simple to use and is compatible with CT scanning, transrectal ultrasound, and the Mick applicator. Its design and key functional features are described here.
Brachytherapy↗
Echocardiographic prediction of left ventricular volume after myocardial infarction.
Left ventricular volume is a strong determinant of survival after acute myocardial infarction. The aim of this study was to determine which clinical and echocardiographic criteria assessed early after myocardial infarction would predict later left ventricular dilation. Forty-eight patients with uncomplicated transmural myocardial infarction had echocardiography 5 to 10 days after myocardial infarction and assessment of clinical variables including peak creatine kinase and sum of electrocardiographic ST segment elevation. Left ventricular dimensions were measured from the echocardiogram in the parasternal view and also in the apical four and two chamber views at the level of the mitral leaflets, papillary muscles and apex. A cardiac wall motion score was obtained by segmental analysis of the apical views. Echocardiographic left ventricular volume was measured after 1 year from the apical views with use of a Simpson's rule method. Initial clinical and echocardiographic variables were correlated with the left ventricular volume at 1 year. There was a significant relation between the initial four and two chamber end-diastolic dimensions and the left ventricular volume at 1 year, particularly for dimensions measured at the apical level (four chamber R2 = 0.66, p = 0.0001, two chamber R2 = 0.61, p = 0.0001). Other clinical variables, parasternal left ventricular dimensions and cardiac wall motion score were not significantly related to left ventricular volume. A powerful three variable model obtained by multiple regression and including the initial two chamber apical dimension, cardiac wall motion score and body surface area accounted for 82% of the variation in left ventricular volume at 1 year.
Cardiac Volume↗
The surface structure seen on gonococci after treatment with CMP-NANA is due to sialylation of surface lipopolysaccharide previously described as a 'capsule'.
Phenotypic serum resistance of gonococci in urethral exudates is due to sialylation of lipopolysaccharide (LPS) by host cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA). A surface structure was visible on gonococci [strain BS4 (agar)] that had been stained with ruthenium red after incubation with CMP-NANA. This structure was not visible after neuraminidase treatment, which released sialic acid but not LPS. The LPS profiles of strain BS4 (agar) had another in vivo-selected strain Gc40 (variant D1), were similar. A monoclonal antibody (mAb) which recognises epitope C on the LPS of 'capsulated' gonococci was shown by immunoblotting to react with several LPS components, including one of about 4.5 kDa which contains the probable site of sialylation by CMP-NANA. The reactions with the mAb were not affected by growing the strains with CMP-NANA nor by neuraminidase treatment of the sialylated LPS. The mAb also gold-labelled the surface of both strains before and after treatment with CMP-NANA. These data indicate that sialylation by CMP-NANA and staining with ruthenium red renders more visible the surface LPS which, sometimes in the past, has been seen as a 'capsule'.
Antibodies, Monoclonal↗
Exacerbation of bacterial toxicity to infant ferrets by influenza virus: possible role in sudden infant death syndrome.
Of several toxins examined, only staphylococcal alpha and gamma toxin, endotoxin, and diphtheria toxins were lethal for 5-day-old ferrets. Their toxicities were enhanced in animals infected at 1 day old with influenza virus, from 3-fold with staphylococcal gamma toxin through 14-fold for staphylococcal alpha toxin, 84-fold for endotoxin, and 219-fold for diphtheria toxin. No increased viral replication occurred in any tissue; thus the effects of the toxins were exacerbated by the infection, not vice versa. Neonates died suddenly without clinical symptoms as in human babies dying from the sudden infant death syndrome (SIDS). Pathologic examination showed inflammation in the upper respiratory tract, lung edema and collapse, and early bronchopneumonia in the toxin- and influenza virus-treated animals but not in those treated with toxin or virus alone. Thus, bacterial toxins could play a role in SIDS, this being more likely with a concomitant influenza virus infection.
Animals↗
Intrapericardial left atrial aneurysm diagnosed by transoesophageal echocardiography and nuclear magnetic resonance imaging.
A case of intrapericardial left atrial aneurysm is described in a 38-year-old woman, who presented with invalidating paroxysmal atrial fibrillation. The diagnosis was suspected by 2D-echocardiography, and confirmed by transoesophageal echocardiography and magnetic resonance imaging. Chest X-ray, right and left ventricular and coronary angiography were normal. The aneurysm was surgically removed, and the patient has subsequently remained free from symptoms.
Adult↗
Influenza virus enhancement of membrane leakiness induced by staphylococcal alpha toxin, diphtheria toxin and streptolysin S.
Release of alpha-amino[14C]isobutyric acid from ferret Mpf cells was promoted by staphylococcal alpha toxin, diphtheria toxin and streptolysin S. This release was enhanced to a significant extent if the cells had been previously infected with influenza virus strain A/Puerto Rico/8/34 (PR8, H1N1), although infection with virus alone did not increase the release of radiolabel as compared with that from untreated cells; inactivated virus had a similar enhancing action. The mechanism of enhancement is unclear but it occurs between 0.5 and 2h post-inoculation and viral membrane/endosome membrane fusion is essential. Endotoxin had no effect on membrane permeability, either alone or with PR8. The relevance of these in vitro observations to the previously observed enhancement of toxin lethality by influenza virus in vivo is discussed.
Aminoisobutyric Acids↗
Nature of the endogenous pyrogen (EP) induced by influenza viruses: lack of correlation between EP levels and content of the known pyrogenic cytokines, interleukin 1, interleukin 6 and tumour necrosis factor.
Fever in influenza results from the release of endogenous pyrogen (EP) following virus-phagocyte interaction and its level correlates with the differing virulence of virus strains. However, the different levels of fever produced in ferrets by intracardial inoculation of EP obtained from the interaction of different virus strains with ferret of human phagocytes did not correlate with the levels of interleukin 1 (IL-1), IL-6 or tumour necrosis factor in the same samples as assayed by conventional in vitro methods. Hence, the EP produced by influenza virus appears to be different to these cytokines.
Animals↗
Non-functional expression of Escherichia coli signal peptidase I in Bacillus subtilis.
The Escherichia coli lep gene, encoding signal peptidase I (SPase I) was provided with Bacillus subtilis transcription/translation signals and expressed in this organism. When present on a low-copy-number plasmid, the amount of E. coli SPase I produced (per mg cell protein) in B. subtilis was half that produced in wild-type E. coli cells. The production of E. coli SPase I in B. subtilis was increased approximately fivefold by cloning the lep gene into a high-copy-number plasmid. The expression of E. coli SPase I in B. subtilis did not appear to increase the rate of processing of two hybrid secretory precursor proteins. Two observations may explain the failure of E. coli SPase I to stimulate processing of exported proteins in B. subtilis. First, the E. coli SPase I was apparently not exposed on the outside of the B. subtilis cytoplasmic membrane, indicating its incorrect insertion into the membrane. Second, in vitro processing studies, using cell-free extracts of B. subtilis producing E. coli SPase I, suggested that the enzyme was not active. A further outcome of this study was that conditions favouring processing of precursors by SPase I in cell-free extracts of E. coli did not favour processing by the corresponding enzyme in B. subtilis cell-free extracts. This suggests that significant differences exist between the two enzymes. The observation that antibodies directed against E. coli SPase I did not cross-react with B. subtilis membrane proteins supports this idea.
Amino Acid Sequence↗