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Biomedical subjects

A Wright

Publications and source records attributed to A Wright.

At least 289 records · Page 16Linked to original sources

A bacterial gene involved in transcription antitermination: regulation at a rho-independent terminator in the bgl operon of E. coli.

We have investigated the mechanism of regulation of the bgl operon in Escherichia coli K-12. A regulatory region has been located downstream of the bgl promoter, revealing a 130 base leader containing a sequence from +64 to +112 characteristic of a rho-independent terminator. In vitro, over 90% of the transcripts initiated at the bgl promoter terminate within the leader, at the 3' end of the terminator. Transcriptional fusions containing the terminator require the bglC gene in trans for expression; fusions deleted for the sequence show bglC-independent expression. A mutation resulting in partially constitutive expression of the fusion maps within the terminator. We propose that the bglC gene product mediates positive regulation of the bgl operon by functioning as an antiterminator at the rho-independent terminator located within the leader.

Base Sequence↗

Prospective study of symptoms and signs in acutely ill infants in general practice.

A study was made of all cases of acute illness in infants aged 6 months or less presenting in a Gosport practice over five months. The frequency in these patients of the well defined symptoms and signs suggested to be important by the preliminary report of the Department of Health and Social Security's multicentre study of postneonatal mortality was recorded. During the study period there were 161 infants of this age in the practice, who gave rise to 69 consultations with acute illness. Thirty eight of these were given drug treatment and five were referred to a paediatric unit, one of them on social grounds. There were no infant deaths in the practice (total population 11,400), but two occurred in the Gosport area (total population 83,000). It would be unrealistic to refer all patients with any one of the symptoms and signs, even when well defined, in the age group 6 months or less. Analysis of the symptoms and signs found in those children who required admission did not show any pattern differentiating them from those who did not. Although the symptoms and signs studied are of value in assessment and should be sought in these patients, they cannot be used singly or in any pattern to indicate referral per se.

Acute Disease↗

Histamine H1-receptor antagonist activity assessed in conscious dogs.

A simple, minimally invasive technique is described which allows assessment of histamine H1-receptor antagonist activity in conscious dogs. The technique is based on the inhibition of the tachycardia caused by intravenous administration of the H1-receptor agonist, 2-pyridylethylamine. The response to 2-pyridylethylamine is dose dependent and is inhibited, in a dose-dependent manner by H1-receptor antagonists, such as temelastine, terfenadine, and chlorpheniramine. In contrast, cimetidine does not inhibit this response. This technique allows comparison of antagonist activity after either oral or intravenous administration of antagonists and also permits an assessment of the time course of antagonism.

Animals↗

The urinary excretion of albumin in normal pregnancy.

The urinary excretion of albumin was measured in a group of normal pregnant women at 14, 28 and 36 weeks gestation and 6 weeks postpartum. Using 2-h urine collections, the excretion rate was not found to increase during pregnancy or to differ from that in a group of non-pregnant controls. The urinary albumin to creatinine concentration ratio was greater at all stages of pregnancy than in the non-pregnant controls and greater at 36 weeks than at 14 weeks gestation. Correcting for the observed changes in serum albumin and creatinine clearance produced evidence consistent with the hypothesis that mean glomerular permeability to albumin rises progressively during pregnancy. Reasons are given why the measurement of urinary albumin excretion may be a useful screening test in some pregnant women, and may also yield useful information on the effect of multiple pregnancies on renal function. One grand multipara was studied and found to have an increased excretion of albumin at each stage of pregnancy.

Albuminuria↗

Haemophilus influenzae immunoglobulin A1 protease genes: cloning by plasmid integration-excision, comparative analyses, and localization of secretion determinants.

Many bacteria which establish infections after invasion at human mucosal surfaces produce enzymes which cleave immunoglobulin A (IgA), the primary immunoglobulin involved with protection at these sites. Bacterial species such as Haemophilus influenzae which produce IgA1 proteases secrete this enzyme into their environment. However, when the gene encoding this protein was isolated from H. influenzae serotype d and introduced into Escherichia coli, the activity was not secreted into the medium but was localized in the periplasmic space. In this study, the IgA1 protease gene (iga) from an H. influenzae serotype c strain was isolated and the gene from the serotype d strain was reisolated. The IgA1 proteases produced in E. coli from these genes were secreted into the growth medium. A sequence linked to the carboxyl terminus of the iga gene but not present in the original clone was shown to be necessary to achieve normal secretion. Tn5 mutagenesis of the additional carboxyl-terminal region was used to define a 75- to 100-kilodalton coding region required for complete secretion of IgA1 protease but nonessential for protease activity. The iga genes were isolated by a plasmid integration-excision procedure. In this method a derivative of plasmid pBR322 containing a portion of the protease gene and the kanamycin resistance determinant of Tn5 was introduced into H. influenzae by transformation. The kanamycin resistance gene was expressed in H. influenzae, but since pBR322 derivatives are unable to replicate in this organism, kanamycin-resistant transformants arose by integration of the plasmid into the Haemophilus chromosome by homologous recombination. The plasmid, together with the adjoining DNA encoding IgA1 protease, was then excised from the chromosome with DNA restriction enzymes, religated, and reintroduced into E. coli. Comparisons between the H. influenzae protease genes were initiated which are useful in locating functional domains of these enzymes.

Amino Acid Sequence↗

Positive and negative regulation of the bgl operon in Escherichia coli.

We have analyzed the functions encoded by the bgl operon in Escherichia coli K-12. Based on the ability of cloned regions of the operon to complement a series of Bgl- point mutations, we show that the three bgl structural genes, bglC, bglS, and bglB, are located downstream of the regulatory locus bglR in the order indicated. Using a bgl-lacZ transcriptional fusion, we show that bglC and bglS are involved in regulating operon expression. The presence of the bglC gene in trans is absolutely required for the expression of the fusion, which is constitutive when only the bglC gene is present. When the bglC and the bglS genes are both present in the cell, expression of the fusion requires a beta-glucoside inducer. From these observations, we conclude that (i) the bglC gene encodes a positive regulatory of bgl operon expression and (ii) the bglS gene encodes a negative regulator of operon expression, causing the requirement for a beta-glucoside inducer. These conclusions are supported by our observations that (i) a majority of bglC mutants exhibits a Bgl- phenotype, whereas rare trans-dominant mutations in bglC result in constitutive expression of the bgl operon and the fusion, and (ii) mutations in the bglS gene lead to constitutive expression of the fusion. Based on several lines of evidence presented, we propose that the bglS gene product has an additional role as a component of the beta-glucoside transport system.

Arbutin↗

Cloning and characterization of dnaA(Cs), a mutation which leads to overinitiation of DNA replication in Escherichia coli K-12.

The product of the dnaA gene is essential for the initiation of chromosomal DNA replication in Escherichia coli K-12. A cold-sensitive mutation, dnaA(Cs), was originally isolated as a putative intragenic suppressor of the temperature sensitivity of a dnaA46 mutant (G. Kellenberger-Gujer, A. J. Podhajska, and L. Caro, Mol. Gen. Genet. 162:9-16, 1978). The cold sensitivity of the dnaA(Cs) mutant was attributed to a loss of replication control resulting in overinitiation of DNA replication. We cloned and sequenced the dnaA gene from the dnaA(Cs) mutant and showed that it contains three point mutations in addition to the original dnaA46(Ts) mutation. The dnaA(Cs) mutation was dominant to the wild-type allele. Overproduction of the DnaA(Cs) protein blocked cell growth. In contrast, overproduction of wild-type DnaA protein reduced the growth rate of cells but did not stop cell growth. Thus, the effect of elevated levels of the DnaA(Cs) protein was quite different from that of the wild-type protein under the same conditions.

Bacterial Proteins↗

Mesulergine and pergolide in previously untreated Parkinson's disease.

Seventeen hitherto untreated patients with mild Parkinson's disease were given the dopamine agonists mesulergine or pergolide. Of the 10 patients who received pergolide (mean dosage 3.7 mg/day) five failed to improve, four showed slight improvement and one gained moderate benefit. Of the seven patients who received mesulergine (mean dose 6.4 mg/day) three patients derived no benefit, two slight benefit and two moderate benefit. The incidence of adverse side-effects was high with both drugs despite the use of a peripheral dopamine receptor antagonist, domperidone, when required. These results are less encouraging than those reported from other centres both in respect of response rate and the severity of unwanted effects.

Aged↗

Use of cerebrospinal fluid gating to improve T2-weighted images. Part I. The spinal cord.

Ungated and gated magnetic resonance images of the spinal cord acquired with the use of long repetition times (TRs) and long echo-delay times (TEs) were compared in 21 studies performed on a 1.5-T system. Both normal and abnormal spinal cord conditions were compared. All images were acquired in an identical fashion except that ungated studies had TRs of 2,000 or 2,500 msec, whereas in gated studies, TR was determined by the patient's heart rate. The effective TR of images gated to the cerebrospinal fluid (CSF) fell primarily in the range of 1,500-1,800 msec. Gating was accomplished using a peripheral pulse. Three image parameters were assessed: signal-to-noise ratio, object contrast, and resolving power. For each parameter, in both normal and abnormal spinal cords, the CSF-gated studies proved superior by eliminating spatially mismapped signal intensity from pulsatile CSF.

Cerebrospinal Fluid↗

Use of cerebrospinal fluid gating to improve T2-weighted images. Part II. Temporal lobes, basal ganglia, and brain stem.

Ungated and gated magnetic resonance images of the temporal lobes, basal ganglia, and brain stem acquired with the use of long repetition times (TRs) and long echo-delay times (TEs), were compared quantitatively. Twenty-five pairs of images obtained on a 1.5-T system were evaluated. Ungated images (TR = 2,000 msec, TE = 80 msec) were acquired in the same manner as gated images except for TR, which, for gated studies, was determined by a patient's heart rate and generally fell into the 1,500-1,800-msec range. Three image parameters were assessed: signal-to-noise ratio (S/N), object contrast, and resolving power. In both normal and abnormal brain tissue, gated images were superior to ungated images in object contrast and resolving power and equivalent in S/N. More so than in comparable studies of the spinal cord, ungated studies were susceptible to both false-positive and false-negative interpretations. As in spinal cord studies, the major benefit of gating was the elimination of phase shift images arising from basal cisterns and the third ventricle.

Basal Ganglia↗

Cervical spine MR imaging: generating high-signal CSF in sagittal and axial images.

Three magnetic resonance (MR) imaging techniques were compared as to their ability to generate images with high-signal cerebrospinal fluid (CSF) to provide a high-contrast CSF-dura interface. The three techniques were CSF gating to the peripheral pulse, selective saturation recovery with gradient refocusing (SSRGR), and gradient recalled acquisition in the steady state (GRASS). In sagittal views of the cervical spine, CSF gating proved to be a reliable technique for producing images with uniform high-signal CSF in a single-section or multi-section mode. In axial views, SSRGR and GRASS techniques were more consistent than CSF gating in producing high-signal CSF images, especially in a multisection mode. Although axial image quality was nearly equivalent for SSRGR and GRASS techniques, the latter was clinically more efficient because of shorter imaging times. These methods of imaging in the cervical spine yield sufficient CSF-dura contrast and spatial resolution to be of use in the diagnosis of cervical disk disease.

Cerebrospinal Fluid↗

CSF-gated MR imaging of the spine: theory and clinical implementation.

A spine phantom and cervical spines of seven volunteers were studied with cerebrospinal fluid (CSF)-gated magnetic resonance imaging to optimize acquisition factors reducing CSF flow artifacts. Peripheral gating was performed with either an infrared reflectance photoplethysmograph or peripheral arterial Doppler signal. The effects of effective repetition time, echo train, trigger delay, number of sections, and imaging plane on image quality were evaluated. Gated imaging of oscillatory CSF motion simulated constant-velocity flow and reduced CSF flow artifacts caused by cardiac-dependent temporal phase-shift effects. Velocity compensation on sagittal even-echo images with a symmetric short-echo time echo train reduced the remaining CSF flow artifacts caused by spatial phase-shift effects. Overall gated imaging time was not increased compared with nongated imaging and was reduced when improved image quality permitted the use of fewer excitations. These results suggest that the combination of CSF gating and flow compensation is clinically useful and efficient because it improves image quality without prolonging imaging time.

Cerebrospinal Fluid↗

Hair cell distributions in the normal human cochlea. A report of a European working group.

Cochlear hair cell counts from individuals who had clinically normal hearing prior to their death have been plotted for various age bands as a function of the number of hair cells per millimetre against their position in the cochlea. Position has been expressed as the distance of that observation of hair cell density from the base of the cochlea, divided by the total length of the cochlea, thereby giving a proportional representation of the cochlea in the range of 0.0 to 1.0 with 20 subdivisions of 0.05. There is an age-related decrease in the number of hair cells in the normal population, and this is more marked for the outer hair cells.

Adolescent↗

Ultrastructural findings on human Scarpa's ganglion.

The morphology of human Scarpa's ganglion from two surgically removed specimens as well as from four autopsy preparations from patients without clinical evidence of vestibular dysfunction was investigated. Ganglion cell circumference varied between 45 and 160 microns. More than half of the nerve cells ranged between 90 and 110 microns. The arrangement of ganglion cells, nerve fibres and endoneural connective tissue appeared better preserved in autopsy preparation than in biopsy specimens. Electron microscopy revealed that in half of the investigated specimens, neuroglial tissue was present as far distal as the vestibular ganglion. Almost all ganglion cells were surrounded by one or several layers of satellite cells, and did not reveal myelination. From the present study we cannot predict if neuronal function in human beings differs from that in other animals, although morphological differences do exist.

Adult↗

Hair cell distributions in the normal human cochlea.

This supplement presents the results of a collaborative project between workers from several European nations. The study was started in order to provide data describing the distribution of the sensory hair cells in the normal human cochlea and to allow the evaluation of age-related changes in the hair cell density. Fifty-three cochleas (including nine from fetuses) were preserved by perilymphatic perfusion with fixative shortly after death. In the non-fetal material the hearing was clinically normal prior to death. Some subjects had audiograms available and these also had to be normal for their age for inclusion of the cochlea in the study. Dissection of cochleas permitted surface preparation techniques to be used to count the hair cells and allow the hair cell density to be described as inner or outer hair cells per mm. The total length in mm of each cochlea was also measured (Length). The location of each hair cell density count was defined as distance in mm from the base (Distance), distance in mm from the apex (Length minus Distance), or as a proportion of the total length of the cochlea when the location of that count was measured as distance from the base (Distance/Length). The material was allocated to one of six age bands. For each age band and at each point in the cochlea for which data existed the average hair cell density and its standard deviation were calculated. This allowed average cytocochleograms to be drawn for both inner and outer hair cells. The proportional method of representation of location within the cochlea gave the best fit of the available data and the proportional cytocochleograms are presented, although the data for all three methods are included in tabular form. The average cytocochleograms indicate a progressive age-related loss of outer hair cells. This loss was exacerbated at both the apical and basal ends of the cochlea. The overall loss was less marked for the inner hair cell population but was accentuated at the base, like that of the inner hair cells, although not at the apex. With the proportional datasets, and taking fetal age as zero, a model of hair cell loss was developed. A simple linear equation in the form: Hair cell density(i) = (Age in years X Age Coefficient(i)) + Constant(i) gave the best fit at each proportional location (i) for both inner and outer hair. The age coefficients and constants are given in tables for inner and outer hair cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Count↗

Diagnostic challenges following cardiac transplantation.

It is now almost two decades since the first human cardiac transplantation was performed. Recipients will require close follow-up by their referring physicians outside of the main referral centers. This article is intended to assist the referring physician in choosing the most appropriate diagnostic studies throughout the posttransplant period.

Biopsy↗