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Biomedical subjects

M J Allen

Publications and source records attributed to M J Allen.

At least 73 records · Page 4Linked to original sources
PubMed1995

A comparison of 'abruptly stopping' with 'tailing off' oral corticosteroids in acute asthma.

Systemic corticosteroids are almost universally used in the treatment of severe acute asthma but the optimum length of treatment with corticosteroids following recovery from an acute attack of asthma is not established. Thirty-five patients admitted with acute asthma and treated with oral prednisolone 40 mg daily in addition to bronchodilator therapy until full recovery, with stable peak expiratory flow recordings (PEF) within 15% of their previous best PEF or predicted PEF were studied. They were all discharged home on regular inhaled corticosteroids and regular or as required use of bronchodilators and randomized to receive either prednisolone 40 mg daily or placebo for the first 14 days. Median PEF values increased from 31% predicted on admission to hospital to 71% predicted on discharge from hospital in the active treatment group (19 patients) and from 32-73% in the placebo group (16 patients). There was no difference between the two groups in the median values of the forced expiratory volume in one second, forced vital capacity, total lung capacity or diurnal variation in PEF either at the time of discharge from hospital or at 14 and 28 days after discharge from hospital. This study suggests that there is no need to reduce prednisolone gradually following recovery from an exacerbation of asthma, provided systemic corticosteroid treatment is continued until a satisfactory and stable PEF is achieved.

Acute Disease↗
PubMed1995

Direct and indirect MRI findings in ganglion cysts of the common peroneal nerve.

MRI findings in three cases of ganglion cyst of the common peroneal nerve are presented. In each case the cyst was imaged as an oval structure in transverse section section adjacent to the fibular neck. The cyst extended in a tubular fashion over several slices with an inferior extension towards the superior tibiofibular joint. Signal intensity was intermediate on T1- and high on T2-weighted images. In addition, increased signal on both T1- and T2-weighted images was noted throughout the peroneal compartment and was associated with clinical and EMG evidence of denervation. This has not been previously described but may be an important indirect sign which, when seen, should prompt a careful search in the region of the fibular neck for an underlying ganglion cyst of the common peroneal nerve.

Adolescent↗
PubMed1995

The value of 99Tcm-MDP bone scans in young patients with exercise-induced lower leg pain.

This study compares the bone scan appearances in 32 patients with medial tibial syndrome (MTS) with the appearance in 28 patients with confirmed chronic compartment syndrome (CCS). A distinctive pattern of uptake was seen in 30 patients, 24 of whom had MTS and 6 of whom had CCS. Of the patients with normal scans, only 4 had MTS, the remaining 15 had CCS. Both of these findings are statistically significant and confirm that bone scans are a useful diagnostic tool in the differential diagnosis of exercise-induced lower leg pain.

Adult↗
PubMed1995

Chronic ankle instability: the value of talar tilt under general anaesthesia.

Ankle inversion injuries are the most common injury in sport and yet treatment is controversial. One result is chronic ankle instability, an injury for which criteria for surgical intervention are unclear. This prospective study of 14 patients showed that a large proportion of patients had no detectable abnormality on preoperative investigation, but were subsequently shown to have an abnormality under general anaesthesia. This suggests that a good history of chronic instability is more sensitive an indicator than conventional investigations. Stress views under anaesthesia may confirm the problem.

Adolescent↗
PubMed1994

Variable germline and embryonic instability of the human minisatellite MS32 (D1S8) in transgenic mice.

Tandem repeat loci such as minisatellites and trinucleotide repeats frequently show instability. We have investigated mutation at human minisatellite MS32 (locus D1S8) transferred to transgenic mice. Three lines of hemizygous transgenic mice were studied. A single-copy line (110D) was seen to be relatively stable, whilst two multicopy lines showed structural instability of the transgene in pedigrees (lines 109 and 110A). For both these lines, mutant structures were detected as a result of mutation events having occurred in the germline or early embryo. Structural changes seen included gain or loss of minisatellite repeat units (110A and 109), alteration of DNA flanking the minisatellite repeat array (109 only) or deletion of the entire transgene (109 only). This work demonstrates that tandem repeat transgenes can show instability and thus provide additional systems for the analysis of repetitive DNA structural change in mice.

Animals↗
PubMed1994

Tandemly repeated transgenes of the human minisatellite MS32 (D1S8), with novel mouse gamma satellite integration.

The human hypervariable minisatellite MS32 has a well characterised internal repeat unit array and high mutation rates have been observed at this locus. Analysis of MS32 mutants has shown that male germline mutations are polarised to one end of the array and frequently involve complex gene conversion-like events, suggesting that tandem repeat instability may be modulated by cis-acting sequences flanking the locus. In order to investigate the processes affecting MS32 mutation rate and mechanism, we have created transgenic mice harbouring an MS32 allele. Here we describe the organisation of eight transgenic insertions. Analysis of these transgenic loci by MVR-PCR and structural analysis of the junctions between mouse flanking DNA and the transgenic loci has shed light on mechanisms of integration and rearrangement of the tandem repeated transgenes. Sequence analysis of the mouse DNA flanking these transgenes has shown that 5 of the 8 insertions have integrated into mouse gamma satellite repeated sequence. This suggests a non-random integration of the MS32 transgene construct into the mouse genome.

Alleles↗
PubMed1994

Rapid refolding of native epitopes on the surface of cytochrome c.

Refolding of surface epitopes on horse cytochrome c has been measured by monoclonal antibody binding. Two antibodies were used to probe re-formation of native-like surface structure: one antibody (2B5) binds to native cytochrome c near a type II turn (residue 44) while the other (5F8) binds to a different epitope on the opposite face of the protein near the amino terminus of an alpha-helical segment (residue 60). The results show that within the first approximately 100 ms of refolding all of the unfolded protein collapses to native-like folding intermediates that contain both antibody binding sites. All three absorbance/fluorescence-detected kinetic phases in the folding of cytochrome c (k1 approximately 5 s-1, k2 approximately 0.4 s-1, k3 approximately 0.03 s-1) are slower than the rates of re-formation of the antibody binding sites (k(obs) > 10.0 s-1), suggesting that the formation of antibody binding sites precedes the refolding reactions observed in kinetically resolved optically-detected refolding phases. Kinetically unresolved folding processes account for 79% and 19% of the total fluorescence change and absorbance change, respectively, observed in equilibrium unfolding. Thus, kinetically unresolved folding reactions appear to be responsible for re-formation of the MAb binding sites within partially folded intermediate species. These species are non-native (incompletely folded) in that their optical properties are in between those of the unfolded and the fully folded protein. As a test of whether antibody binding to folding intermediate(s) perturbs further folding, the rate of the absorbance-detected slow refolding phase has been measured for folding intermediate(s) of cytochrome c complexed with antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Management of non-palpable breast lesions detected mammographically.

A total of 212 consecutive fine-wire localization breast biopsies in 202 patients were performed on impalpable mammographically suspicious lesions. Preoperative fine-needle aspiration cytology was performed on 159 lesions and was valuable in planning the extent of the fine-wire localization biopsy. All 212 target lesions were accurately biopsied during the initial surgery. Overall, 134 lesions were malignant and 78 benign (benign:malignant ratio 1:1.72), with fewer biopsies for benign lesions performed in screened patients (benign:malignant ratio 1:2.43) than in those with symptoms (ratio 1:1). Breast conservation was achieved in 72 patients (80 per cent) with screen-detected in situ or invasive carcinoma and in 19 of 37 presenting via a symptomatic clinic. In 160 of 202 patients (79 per cent) the initial fine-wire localization biopsy was diagnostic and therapeutic.

Biopsy, Needle↗
PubMed1994

Use of vectorette and subvectorette PCR to isolate transgene flanking DNA.

Vectorette PCR permits the specific amplification of DNA segments flanking a known DNA sequence. It enables the application of the PCR where sequence information is only available for one primer site. We now show that vectorette PCR can be used for the systematic mapping and retrieval of transgene flanking DNA. We also show that the sequence of large vectorette PCR fragments can be obtained without cloning, by the production of subvectorette fragments.

Animals↗
PubMed1993

Atomic force microscope measurements of nucleosome cores assembled along defined DNA sequences.

We have found that the atomic force microscope (AFM) can be used to image the "beads-on-a-string" chromatin structure in a normal air environment following adsorption onto a cover glass substrate. Individual nucleosome cores and linker DNA could be resolved clearly along chromatin fibers that were reconstituted using histone octamers and a tandemly repeated 208-bp nucleosome positioning DNA sequence (208-18). AFM measurements showed that the compaction of the 3780-bp DNA by different loadings of histone octamers was consistent with 146 bp of DNA wrapped 1.75 turns about the histone octamer to form the 11-nm nucleosome core. Precise internucleosome core spacing measurements could be performed along the chromatin fiber axis. In other experiments, AFM images of chromatin reconstituted using closed circular DNA showed highly tangled beaded fibers, as expected. These images and measurements demonstrate that AFM can provide useful high-resolution structural information about chromatin that can be used to complement other more established techniques such as electron microscopy.

Animals↗
PubMed1993

Identification of the elemental packing unit of DNA in mammalian sperm cells by atomic force microscopy.

DNA is packaged within the sperm cell nuclei of many vertebrates and all mammals in a highly condensed state by small basic proteins (protamines). Despite continuous investigation for nearly half a century, the actual packing arrangement of the DNA has remained unresolved. Atomic force and electron microscopy studies described in this report provide evidence that the fundamental packing unit for sperm DNA is a toroidal structure, 900A in outside diameter with a 150A diameter hole, which contains up to 60kb of DNA. Although the results presented here are based primarily upon investigations of mammalian sperm cells, they are expected to be valid for all sperm cells which utilize protamines to package DNA.

Animals↗
PubMed1993

Atomic force microscopy of mammalian sperm chromatin.

We have used the atomic force microscope (AFM) to image the surfaces of intact bull, mouse and rat sperm chromatin and partially decondensed mouse sperm chromatin attached to coverglass. High resolution AFM imaging was performed in air and saline using uncoated, unfixed and unstained chromatin. Images of the surfaces of intact chromatin from all three species and of an AFM-dissected bull sperm nucleus have revealed that the DNA is organized into large nodular subunits, which vary in diameter between 50 and 100 nm. Other images of partially decondensed mouse sperm chromatin show that the nodules are arranged along thick fibers that loop out away from the nucleus upon decondensation. These fibers appear to stretch or unravel, generating narrow smooth fibers with thicknesses equivalent to a single DNA-protamine complex. High resolution AFM images of the nodular subunits suggest that they are discrete, ellipsoid-shaped DNA packaging units possibly only one level of packaging above the protamine-DNA complex.

Animals↗
PubMed1993

Popliteal entrapment syndrome: misdiagnosed as a compartment syndrome.

We report a case of popliteal artery entrapment syndrome which was originally diagnosed as a chronic compartment syndrome. The relative occurrence of the two conditions and their very similar symptoms explain the misdiagnosis. The diagnostic methods and surgical treatment for both conditions are discussed and suggestions are made as to possible non-invasive screening methods.

Adult↗
PubMed1993

Dose-ranging effects of candoxatril on elimination of exogenous atrial natriuretic peptide in chronic heart failure.

Seven patients with chronic heart failure were treated in single-blind crossover fashion with placebo and 10 mg, 50 mg, and 200 mg doses of the neutral endopeptidase inhibitor candoxatril to determine the effects of candoxatril on the elimination kinetics of exogenously infused atrial natriuretic peptide (ANP). An incremental dose-response effect was observed on the mean maximum observed plasma concentration (Cmax) of the active metabolite candoxatrilat (107.4, 453.5, and 1584 ng/ml in response to 10, 50, and 200 mg candoxatril, respectively). Pooled active versus placebo comparisons showed that candoxatril reduced the clearance (p = 0.021) and elimination rate constant (p = 0.006) and increased Cmax (p = 0.002) and time to reach Cmax (p = 0.01) of exogenous ANP. Individually, both 50 mg and 200 mg but not 10 mg candoxatril significantly altered the elimination kinetics of ANP. The most favorable effects were observed in response to 200 mg candoxatril, although even this dose may not have achieved the maximal modulating effect on elimination of circulating ANP.

Aged↗