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Biomedical subjects

P Laing

Publications and source records attributed to P Laing.

At least 19 recordsLinked to original sources
PubMed2005

Early results of autologous chondrocyte implantation in the talus.

Autologous chondrocyte implantation (ACI) has been used most commonly as a treatment for cartilage defects in the knee and there are few studies of its use in other joints. We describe ten patients with an osteochondral lesion of the talus who underwent ACI using cartilage taken from the knee and were prospectively reviewed with a mean follow-up of 23 months. In nine patients the satisfaction score was 'pleased' or 'extremely pleased', which was sustained at four years. The mean Mazur ankle score increased by 23 points at a mean follow-up of 23 months. The Lysholm knee score returned to the pre-operative level at one year in three patients, with the remaining seven showing a reduction of 15% at 12 months, suggesting donor-site morbidity. Nine patients underwent arthroscopic examination at one year and all were shown to have filled defects and stable cartilage. Biopsies taken from graft sites showed mostly fibrocartilage with some hyaline cartilage. The short-term results of ACI for osteochondral lesions of the talus are good despite some morbidity at the donor site.

Adolescent↗
PubMed2000

Immunisation with phage displaying peptides representing single epitopes of the glycoprotein G can give rise to partial protective immunity to HSV-2.

Filamentous phage displaying peptides representing single epitopes of the glycoprotein G of HSV-2 (gG2) were used as immunogens via the subcutaneous route in Balb/c mice without additional adjuvant. The phage were isolated from a random phage peptide display library and contain 15-mer peptide inserts that mimic epitopes of gG2. In each case, an antibody response to gG2 was generated that was dependent on the dose of phage administered and on the presence of the peptide insert. Phage displaying epitopes of gG2, which map to amino acids 551-570, were the most immunogenic; interestingly, this region of gG2 is frequently recognised by patients infected with HSV-2. The data also provide interesting information as regards choice of peptide mimics for use as immunogens because, surprisingly, the most antigenic of the individual clones was the least immunogenic. In two of the experiments, mice immunised with phage displaying a single epitope of gG2 were protected against challenge with a lethal dose of whole HSV-2. This suggests a possible role for phage-displayed peptides in inducing protective immunity against pathogens and provides a model system for investigating the underlying mechanisms.

Amino Acid Sequence↗
PubMed2000

Influenza virus infection in the second and third trimesters of pregnancy: a clinical and seroepidemiological study.

OBJECTIVE: To determine whether maternal influenza virus infection in the second and third trimesters of pregnancy results in transplacental transmission of infection, maternal auto-antibody production or an increase in complications of pregnancy. DESIGN: Case-control cohort study. POPULATION: Study and control cohorts were derived from 3,975 women who were consecutively delivered at two Nottingham teaching hospitals between May 1993 and July 1994. A complete set of three sera was available for 1,659 women. METHODS: Paired maternal ante- and postnatal sera were screened for a rise in anti-influenza virus antibody titre by single radial haemolysis and haemagglutination inhibition. Routine obstetric data collected during and after pregnancy were retrieved from the Nottingham obstetric database. Cord samples were tested for the presence of IgM anti-influenza antibodies, and postnatal infant sera were tested for the persistence of influenza-virus specific IgG. Paired antenatal and postnatal sera were tested against a standard range of auto-antigens by immunofluorescence. MAIN OUTCOME MEASURES: Classification of women as having definite serological evidence of an influenza virus infection in pregnancy (cases) or as controls. RESULTS: Intercurrent influenza virus infections were identified in 182/1,659 (11.0%) pregnancies. None of 138 cord sera from maternal influenza cases was positive for influenza A virus specific IgM. IgG anti-influenza antibodies did not persist in any of 12 infant sera taken at age 6-12 months. Six of 172 postnatal maternal sera from cases of influenza were positive for auto-antibodies. In all cases the corresponding antenatal serum was also positive for the same auto-antibody. There were no significant differences in pregnancy outcome measures between cases and controls. Overall, there were significantly more complications of pregnancy in the cases versus the controls, but no single type of complication achieved statistical significance. CONCLUSIONS: Influenza infection in the second and third trimesters of pregnancy is a relatively common event. We found no evidence for transplacental transmission of influenza virus or auto-antibody production in pregnancies complicated by influenza infections. There was an increase in the complications of pregnancy in our influenza cohort.

Adolescent↗
PubMed1999

Identification of type-specific domains within glycoprotein G of herpes simplex virus type 2 (HSV-2) recognized by the majority of patients infected with HSV-2, but not by those infected with HSV-1.

A combination of phage peptide display library mapping and pepscanning, with both murine monoclonal antibodies and a panel of well-characterized human sera, have been used in order to define type-specific epitopes of glycoprotein G of herpes simplex virus type 2 (HSV-2) (gG2). Both techniques revealed an immunodominant region of gG2, centred around amino acids 525-587 of the uncleaved gG2 molecule. A soluble peptide, equivalent to amino acids 551-570, when used as antigen in an ELISA format was recognized by three out of five murine MAbs and by 20/26 (77%) Western blot anti-HSV-2-positive human sera, but by only 1/63 Western blot anti-HSV-2-negative sera (specificity, 98%). The sensitivity of detection of human anti-HSV-2 antibodies was increased to 90% using a peptide derived from this region, presented on a nitrocellulose membrane. This highly antigenic and type-specific domain of gG2 is located at the junction between the 'unique' region of gG2 and its C-terminal end, which has approximately 50% identity with gG1. A second antigenic region of gG2, amino acids 351-427, which lies within the 'unique' part of gG2, was also identified by both techniques employed in this study and is recognized by a proportion of anti-HSV-2-positive sera. These findings demonstrate the feasibility of developing a peptide-based type-specific assay for the detection of anti-HSV-2 antibody in human sera based on type-specific epitopes of gG2 and have implications for the understanding of the three-dimensional topography of gG2.

Amino Acid Sequence↗
PubMed1998

The development and complications of diabetic foot ulcers.

Neuropathy and ischemia, two common complications of diabetes mellitus, are the primary underlying risk factors for the development of foot ulcers and their complications. The presence of symmetric distal polyneuropathy, encompassing motor, sensory, and autonomic involvement, is one of the most important factors in the development of diabetic foot ulcers. Perhaps one third of diabetic foot ulcers have a mixed neuropathic and ischemic etiology. Although neuropathy and ischemia are the primary predisposing factors in the formation of diabetic foot ulcers, an initiating factor, such as physical or mechanical stress, is required for an ulcer to develop. Ischemic ulcers develop as a result of low perfusion pressure in a foot with inadequate blood supply, whereas neuropathic ulcers result from higher pressures in a foot with adequate blood supply but loss of protective sensation. In addition to increasing the risk of ulceration, diabetes mellitus also increases the risk of infection by impairing the body's ability to eliminate bacteria. The processes by which ulcers develop are reviewed here.

Bacterial Infections↗
PubMed1998

Epidural spinal cord stimulation for treatment of chronic pain--some predictors of success. A 15-year experience.

BACKGROUND: We have used epidural spinal cord stimulation (SCS) for pain control for the past 15 years. An analysis of our series of 235 patients has clarified the value of specific prognostic parameters in the prediction of successful SCS. METHODS: Patients were followed up for periods ranging from 6 months to 15 years with a mean follow-up of 66 months. The mean age of the 150 men and 85 women in the study was 51.4 years. Indications for SCS included failed back syndrome (114 patients), peripheral vascular disease (39 patients), peripheral neuropathy (30 patients), multiple sclerosis (13 patients), reflex sympathetic dystrophy (13 patients), and other etiologies of chronic intractable pain (26 patients). RESULTS: One hundred and eighty-nine patients received permanent devices; 111 (59%) of these patients continue to receive satisfactory pain relief. Pain attributable to failed back syndrome, reflex sympathetic dystrophy, peripheral vascular disease of lower limbs, multiple sclerosis, and peripheral neuropathy responded favorably to spinal cord stimulation. In contrast, paraplegic pain, cauda equina syndrome, stump pain, phantom limb pain, and primary bone and joint disease pain did not respond as well. Cases of cauda equina injury had promising initial pain relief, but gradually declined after a few years. After long-term follow-up, 47 of the 111 successfully implanted patients were gainfully employed, compared with 22 patients before implantation. The successful patients reported improvements in daily living as well as a decrease in analgesic usage. Multipolar stimulation systems were significantly more reliable (p < 0.001) than unipolar systems. Complications included hardware malfunction, electrode displacement, infection, and tolerance. CONCLUSION: Aside from etiologies of pain syndromes as a prognostic factor, we have identified other parameters of success. In patients who have undergone previous surgical procedures, the shorter the duration of time to implantation, the greater the rate of success (p < 0.001). The diagnosis of failed back syndrome must be considered a confounding factor in our analysis. Those patients whose pain did not follow a surgical procedure had better responses to SCS than patients who had multiple surgical procedures prior to their first implant. The advent of multipolar systems has significantly improved clinical reliability over unipolar systems. Age, sex, and laterality of pain did not prove to be of significance.

Adult↗
PubMed1997

Cleavage of the low-affinity receptor for human IgE (CD23) by a mite cysteine protease: nature of the cleaved fragment in relation to the structure and function of CD23.

Der p I, a cysteine protease representing a major allergen of the house dust mite Dermatophagoides pteronyssinus, has recently been shown to cleave CD23 from the surface of cultured human B cells (RPMI 8866 B cell line). We have now undertaken a detailed investigation of CD23 cleavage by Der p I. We demonstrate that Der p I cleaves CD23 at two sites (Ser155-Ser156 and Glu298-Ser299) to produce a 17-kDa fragment containing the lectin domain and only part of the C-terminal tail. No such effect was demonstrable with mouse CD23, a finding which was anticipated based on its lack of the cleavage sites identified on human CD23. Based on the cleavage pattern and the model of CD23, we propose a sequence of events leading to the liberation of the 17-kDa soluble CD23 fragment. The biological significance of such cleavage is underlined by the demonstration that Der p I-treated B lymphocytes lose their ability to bind IgE, and that the 17-kDa fragment (amino acids 156-298) contains the minimum structural requirement (amino acids 156-288) for binding to both IgE and CD21.

Animals↗
PubMed1996

Rhesus incompatibility as a risk factor for schizophrenia in male adults.

BACKGROUND: Rhesus (Rh) incompatibility is a cause of hemolytic disease of the fetus and newborn. Hemolytic disease results from the transplacentally transmitted maternal antibodies against Rh factor D and can cause permanent neurological damage in the affected newborn. This study examines the hypothesis that Rh incompatibility may be a risk factor for schizophrenia. METHODS: A sample of 1867 male subjects was divided into two groups, 535 Rh incompatible and 1332 Rh compatible, and compared on rate of schizophrenia. RESULTS: The rate of schizophrenia was significantly higher in the Rh-incompatible group (2.1%) compared with the Rh-compatible group (0.8%) (P < .03). In addition, since the risk for Rh hemolytic disease increases with second and later Rh incompatible pregnancies, it is noteworthy that the second- and later-born incompatible offspring exhibited a significantly higher rate of schizophrenia than second- and later-born compatible offspring (P < .05). Also, as predicted, the rate of schizophrenia among firstborn incompatible subjects was not significantly different from that of firstborn compatible subjects (1.1% vs 0.7%). CONCLUSION: Rh incompatibility may be a risk factor for schizophrenia.

Adult↗
PubMed1996

Screening for patients at risk of diabetic foot ulceration in a general diabetic outpatient clinic.

An examination of the reproducibility of three tests for identifying patients at risk of diabetic foot complications is reported. One thousand and one patients attending a general diabetic outpatient clinic at the Royal Liverpool University Hospital underwent screening using the Semmes-Weinstein monofilaments, the biothesiometer, and palpation of pedal pulses. Two hundred and fifty-nine patients who were found to have a deficit on at least one of these tests were given a second appointment where the tests were repeated. Two hundred and twenty-nine patients attended for their second appointment. The expected range of variation in readings for the biothesiometer was 5 log hertz, sufficient variation to make the biothesiometer unacceptable as a screening instrument. The range of reproducibility for the four pedal pulses was from 68% to 81%, also an unacceptable level of variation. Over 85% of the results for the Semmes-Weinstein monofilaments were the same on the first and second measurement. Of the three instruments examined in this study, only the Semmes-Weinstein monofilaments have sufficient reproducibility in the clinical setting for them to be recommended for general use as a screening test for risk of diabetic foot complications.

Adolescent↗
PubMed1996

Multiple sclerosis: sunlight, diet, immunology and aetiology.

Multiple sclerosis is more common in temperate latitudes, and migration studies indicate the involvement of an aetiological environmental factor in pre-pubertal life; the precise nature of this factor has never been identified and may perhaps have been overlooked. Here we suggest a simple explanation for the latitude gradient of multiple sclerosis, i.e. that it can be explained by the immunosuppressant effects of sunlight mediated via suppression of the secretion of the immunostimulatory neurohormone melatonin from the pineal gland. The effects of dietary fatty acids in multiple sclerosis also indicate the involvement of anti-inflammatory eicosanoids in its pathogenesis. We further suggest that the exceptions to the latitude gradient (e.g. Japan), which have previously been attributed to genetic factors, may in fact have a dietary basis. Since sunlight also influences the metabolism of fatty acids in the retina, it may also influence the development of retrobulbar optic neuritis-a common antecedent of multiple sclerosis. We suggest a re-examination of the epidemiology of multiple sclerosis based on an understanding of the immunological consequences of illumination of the retina by sunlight.

Autoimmunity↗
PubMed1996

Diagnosis of osteomyelitis in neuropathic foot ulcers.

We reviewed all patients with a clinically infected foot ulcer attending a specialised neuropathic foot clinic. Neuropathy was confirmed by the inability to feel a 5.07 Semmes-Weinstein hair, areflexia and impaired vibration sense, as measured by a biothesiometer. Of 40 patients who attended the clinic over a two-year period, six with ischaemic ulcers were excluded. The remaining 34 had plain radiographs of the foot followed by a 99mTc-MDP bone scan. If the latter was positive, an 111In-labelled WBC scan was performed with planar and/or tomographic dual-isotope studies where appropriate. Bone and WBC scans were performed in 31 patients. In ten, isotope imaging showed infection localised to the soft tissues only and conservative treatment was successful in them all. Eighteen patients were treated surgically with excision of the involved bone, which was sent for culture and histological examination. Dual-isotope scans had a sensitivity of 93% and a specificity of 83%. 99mTc-MDP bone scans with the appropriate In-labelled WBC scans can reliably determine the site and extent of osteomyelitis in the neuropathic diabetic foot.

Bone and Bones↗
PubMed1995

Der p I, a major allergen of the house dust mite, proteolytically cleaves the low-affinity receptor for human IgE (CD23).

The nature of the proteases that cleave CD23 in vivo is of considerable interest, but remains unknown. Here, we demonstrate that Der p I, a major allergen of the house dust mite Dermatophagoides pteronyssinus, cleaves CD23 from the surface of cultured human B cells (RPMI 8866 B cell line). The cleavage of the receptor from the B cell surface was associated with a parallel increase in soluble CD23 (sCD23) in the culture supernatant. Furthermore, the proteolytic effect of Der p I was specific for CD23, since none of the other B cell markers tested (CD20, HLA-DR, CD71 and CD49d) were affected. Labeled antibody experiments and protease inhibition assays clearly demonstrate that Der p I is a cysteine protease that directly cleaves a 25-kDa fragment of CD23. These data suggest that the cysteine protease Der p I, in addition to being highly immunogenic, may up-regulate IgE synthesis by virtue of its ability to cleave CD23.

Allergens↗
PubMed1995

Selection of peptide ligands for the antimucin core antibody C595 using phage display technology: definition of candidate epitopes for a cancer vaccine.

Aims-To further define the specificity of the antimucin core antibody C595 by fitting it with a family of hexapeptide ligands by immunoselection of filamentous bacteriophage from a gene III display library of approximately 6.4 x 10(7) random hexapeptides.Methods-Three rounds of immuno-selection were used to enrich for C595 binding phage. DNA sequencing revealed the hexapeptides expressed. Bacteriophage and corresponding synthetic hexapeptides were used in ELISA assay to determine binding affinities.Results-Twenty nine clones from this selected population were analysed. Seven contained the natural epitope RPAP, encoded by two different DNA sequences; 17/29 contained the motif RLPP. In all, 28/29 clones contained the motif RXXP and one clone (RVRPAP) contained the motif RXXP in two peptidic registers; 24/28 clones (6/8 DNA sequences) contained a hydrophobic residue (V or I) at position 1 relative to the RXXP motif. In addition the proximity of RXXP to glycine (position 5) suggests that this contributes in the natural epitope to antibody/antigen binding, which was not detected by chemical synthetic methods. One clone, KSKAGV, bears no obvious relationship to the natural epitope and therefore qualifies as a weakly binding mimotope.Conclusions-This approach has rapidly defined the specificity of this antibody in unprecedented detail, and provides a more comprehensive molecular basis for exploring the immune recognition of the MUC1 mucin by the C595 antibody. Importantly, the novel but related epitopes seen provide peptide specificities and a strategy which may prove useful in generating cancer vaccine candidates.

Journal Article↗
PubMed1995

Effect of the shoe on plantar foot pressures.

The bare foot plantar pressures were compared to in-shoe pressure measurements in 11 normal male volunteers using the EMED system. Shoes diminished pressures and forces in most areas under the foot except the medial forefoot. The hallux showed less force, a smaller contact area and a reduced contact time. Therefore a shoe can interfere with the toe-off mechanism. There was no difference between various types of shoes with rubber and leather soles. Heavier subjects tended to put less weight on the medial forefoot.

Adult↗
PubMed1994

Diabetic foot ulcers.

Neuropathic and vascular changes in patients with diabetes mellitus put them at risk for developing chronic foot wounds after minor trauma or after pressure has caused a breakdown in the integrity of the skin. Accurate diagnosis of the underlying cause is the first step toward a successful treatment plan, and in patients with severe ischemia, vascular reconstruction may be needed. Neuropathic ulcers respond well to less-invasive procedures, particularly when combined with reducing the pressure that caused the ulcer. When pressure is relieved by means of total contact casting, necrotic materials are removed, and protection is secured with a hydrocolloid dressing, these wounds have been found to heal, on an outpatient basis, after approximately 6 weeks. All diabetic foot ulcers are contaminated with a variety of organisms, but antibiotic treatments are usually unnecessary. When signs of a clinical infection are present and/or bone is exposed, osteomyelitis should be suspected. In these patients, aggressive surgical debridement, systemic antibiotics, and meticulous wound care regimens to restore the body's own bacterial barrier will often prevent amputation, the most serious complication of these wounds.

Diabetic Foot↗
PubMed1993

Many spinal cord cells transiently express low molecular weight forms of glutamic acid decarboxylase during embryonic development.

At early developmental stages in the rat spinal cord (embryonic day 13), when neuronal progenitors are still proliferating, most differentiating neurons express truncated forms of glutamic acid decarboxylase (GAD) (approximately 25 kDa) which are the products of alternative splicing of the GAD67 gene. These truncated proteins do not appear to synthesize gamma-aminobutyric acid (GABA). The amino acid is detected in cells only after alternative splicing of the GAD67 gene generates a full-length, 67 kDa enzymatically active form of GAD. Both the 67 kDa GAD and GABA colocalize and appear diffusely distributed in the cytoplasm of embryonic neurons. GABA does not appear associated with synaptic vesicles until after birth, when its intracellular distribution becomes punctate and it colocalizes with synaptophysin. At this time, it also colocalizes with an immunologically distinct 65 kDa GAD protein encoded by a second GAD gene (GAD65). Expression of different GAD-related proteins with distinct intracellular distributions during development suggests that GABA, the product of these enzymes, may have trophic or metabolic roles during spinal cord differentiation.

Animals↗