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Biomedical subjects

M Lyons

Publications and source records attributed to M Lyons.

At least 19 recordsLinked to original sources
PubMed2006

Chick embryo lethal orphan virus can be polymer-coated and retargeted to infect mammalian cells.

Non-human adenovirus vectors have attractive immunological properties for gene therapy but are frequently restricted by inefficient transduction of human target cells. Using chicken embryo lethal orphan (CELO) virus, we employed a nongenetic mechanism of polymer coating and retargeting with basic fibroblast growth factor (bFGF-pc-CELOluc), a strategy that permits efficient tropism modification of human adenovirus. bFGF-pc-CELOluc showed efficient uptake and transgene expression in chick embryo fibroblasts (CEF), and increased levels of binding and internalization in a variety of human cell lines. Transgene expression was also greater than unmodified CELOluc in PC-3 human prostate cells, although the specific activity (RLU per internalized viral genome) was decreased. In CEF, the specific activity of bFGF-pc-CELOluc was considerably higher than in the human prostate cell line PC-3. Retargeted virus was fully resistant to inhibition by human serum with known adenovirus-neutralizing activity in vitro, while in mice CELOluc was cleared less rapidly from the blood than Adluc following i.v. administration in the presence of adenovirus neutralizing serum. Polymer coating and retargeting with bFGF further reduced rates of clearance for both viruses, suggesting protection against both neutralizing and opsonizing factors. The data indicate that CELO virus may be retargeted to infect human cells via alternative, potentially disease-specific, receptors and resist the effects of pre-existing humoral immunity.

ATPases Associated with Diverse Cellular Activitie↗
PubMed2006

Gene transfer into rat mesenchymal stem cells: a comparative study of viral and nonviral vectors.

Mesenchymal stem cells (MSCs) have been proposed for use in combinatorial gene and cell therapy protocols for the treatment of disease and promotion of repair. The efficacy of such a therapeutic approach depends on determination of which vectors give maximal transgene expression with minimal cell death. The study was carried out on bone-marrow derived rat MSCs, and a range of vectors was tested on the same stem cell preparation. Adenovirus, adeno-associated virus (AAV; serotypes 1, 2, 4, 5, and 6), lentivirus, and nonviral vectors were compared. Lentivirus proved to be most effective with transduction efficiencies of up to 95%, concurrent with low levels of cell toxicity. Adenovirus also proved effective, but a significant increase in cell death was seen with increasing viral titer. Rat MSCs remained refractory to transduction by all AAV serotypes, in contrast to rabbit MSCs tested at the same time. Lipofection of plasmid DNA gave moderate transfection levels but was also accompanied by cell death. Electroporative gene transfer proved ineffective at the parameters tested and resulted in high cell death. High and moderate levels of cell transduction using lentivirus vectors did not affect the ability of the cells to differentiate down the adipogenic pathway.

Adenoviridae↗
PubMed2004

Audit of referrals for head and neck cancer - the effect of the 2-week, fast track referral system.

The NHS Cancer Plan sets out targets for the diagnosis and treatment of cancer. Ideally, there should be a maximum of a 2-week wait from a referral for suspected cancer to an outpatient appointment. A fast track referral system has been established nationally, with general practitioners given guidelines as to appropriate referrals. In the South Essex region, we audited all such referrals using this system for a 12-month period and also all new patients diagnosed with head and neck cancer during the same period. We found that 71% of patients diagnosed with cancer were not referred using the fast track system and that only 15% of patients who were referred by the fast track system were subsequently found to have cancer. For patients with cancer who were referred using standard letters, the time from referral to initial consultation was generally much longer than the recommended period of 2 weeks. We conclude that improvements in utilizing the fast track system need to be made if it is to bring about an improvement in early diagnosis of head and neck cancer. As things stand, it may actually be detrimental for most cancer patients.

Ambulatory Care↗
PubMed2002

Orthostatic headache syndrome with CSF leak secondary to bony pathology of the cervical spine.

The syndrome of orthostatic (low pressure) headaches is well described and most commonly occurs following deliberate violation of the dura (e.g. lumbar puncture). This syndrome can also occur spontaneously and results from the leakage of CSF. We describe three patients who suffered from spontaneous CSF leaks secondary to bony pathology of the cervical spine, and propose that this may be a more common aetiology than originally thought. Often these patients are difficult to manage medically, and surgery may be necessary for symptomatic relief.

Adult↗
PubMed2002

Tuberculosis in an indigenous young white south Wales population.

Concerns about tuberculosis in young people in two linked deprived non-metropolitan communities triggered an investigation into local disease incidence and control measures. A pragmatic case-finding exercise, epidemiological enquiry and DNA genotyping were carried out to establish incidence and connections between cases over a five-year period. Of the 91 cases identified, 88 were from the white indigenous population. Approximately one third of cases were aged under thirty. Eight disease clusters were identified. Epidemiological investigation found spurious links between these, and DNA genotyping was necessary to clarify links. Seven cases and several contacts had been in prisons throughout the United Kingdom. Index cases under thirty generated more contacts, more contacts needing prophylaxis and more secondary cases than older patients. The workload resulting from tuberculosis control in younger cases was considerable. Tuberculosis remains an important problem in this population.

Adolescent↗
PubMed2001

B-cell dysfunction and depletion using mycophenolate mofetil in a pediatric combined liver and kidney graft recipient.

The use of mycophenolate mofetil (MMF) in combination with cyclosporin A (CsA) and steroids is well established after kidney transplantation (Tx) in children. A 9-yr-old girl with primary hyperoxaluria type 1 and systemic oxalosis underwent a combined kidney and liver Tx at our institution. The post-operative immunosuppression consisted of CsA, prednisolone, and MMF. Four weeks post-transplant the girl suffered from a severe urinary tract infection caused by Pseudomonas aeruginosa, when the serum immunoglobulin G (IgG) concentration was found to be critically low (<1.53 g/L). Additionally, there was an isolated B-cell depletion (240/microL) at that time. In the following course, the B-cell count was significantly diminished until the MMF was stopped 13 weeks post-transplant. As a result of the very low serum IgG concentration, intravenous immunoglobulin (IVIG) substitution was necessary. There was no significant loss of immunoglobulins in the ascites and urine and no other medication with possible side-effects on B cells was given. We suggest that MMF can lead to suppressed IgG production by B cells and can cause a defective differentiation into mature B cells. In vitro studies demonstrated these effects of MMF on B cells, but no in vivo cases of this phenomenon have been reported. B-cell counts and serum IgG concentrations returned to normal values after discontinuing the MMF. As we can assume that the observed B-cell dysfunction and depletion were MMF related, we suggest that serum IgG concentrations should be monitored when MMF is used after solid-organ Tx.

B-Lymphocytes↗
PubMed2001

Effect of low doses of ionizing radiation on cells cultured from the hematopoietic tissue of the Dublin Bay prawn, Nephrops norvegicus.

Explant cultures from the hematopoietic tissue of the Dublin Bay prawn, Nephrops norvegicus, were exposed to low doses of (60)Co gamma radiation. Cells growing from the explants were examined 7 days after irradiation using light and transmission electron microscopy and were also tested for their ability to produce signals indicative of a bystander effect. The exposed cultures displayed pronounced damage and were orders of magnitude more sensitive than the data in the literature would suggest for arthropod cells. The cultures were also more sensitive than mammalian cells that were exposed to similar doses. Cellular abnormalities included damage to cytoplasmic organelles, particularly the cytoskeleton. Abnormal mitochondria were also prominent. At low doses (0.5 Gy), nuclear damage was not apparent in the cultures, but there was evidence of a dose-dependent increase in apoptosis. The irradiated cultures released a factor into the medium that was capable of inducing apoptosis and cell death in unirradiated fish and human cells. This bystander effect was of a similar magnitude to that reported for mammalian cell systems. It is suggested that these crustaceans may be highly sensitive to radiation, unlike terrestrial arthropods and certain other invertebrates, which are generally considered to be radioresistant.

Animals↗
PubMed2000

The effect of family status and schizotypy on electrophysiologic measures of attention and semantic processing.

BACKGROUND: Disturbances in both attention and language are central to the phenomenology of the schizophrenia spectrum disorders. The purpose of this study was to investigate the relative contributions of two factors, family status and schizotypy, on electrophysiologic measures of attention and semantic processing in family members of individuals with schizophrenia. METHODS: Fifteen first-degree relatives of individuals with schizophrenia and 15 comparison subject controls participated in diagnostic evaluations, an assessment of schizotypy, and two event-related potential (ERP) paradigms. The first paradigm was an auditory P300 "oddball" task designed to assess attentional functioning. The second was an N400 sentence paradigm particularly sensitive to language processing. RESULTS: Both relatives and individuals higher in schizotypy, but not their respective comparison groups, showed reductions in P300 amplitude. In the N400 paradigm, individuals higher in schizotypy, but not relatives, showed a reduced N400 effect. There were no differences in latency for either group on either component. CONCLUSIONS: The results suggest that both family status and schizotypal presentation independently contribute to disturbances in electrophysiologic measures sensitive to attention and language. Whereas higher levels of schizotypy appear to be associated with disturbances in both attention and language processing, family membership appears to place individuals at risk for attentional deficits alone.

Adult↗
PubMed2000

Dimensions and categories: the "big five" factors and the DSM personality disorders.

The five-factor model of personality, which has been widely studied in personality psychology, has been hypothesized to have specific relevance for DSM-defined personality disorders. To evaluate hypothesized relationships of the five-factor model of personality to personality disorders, 144 patients with personality disorders (diagnosed via a structured interview) completed an inventory to assess the five-factor model. Results indicated that the majority of the personality disorders can be differentiated in theoretically predictable ways using the five-factor model of personality. However, while the personality disorders as a whole appear to be differentiable from normal personality functioning on the five factors, the patterns are quite similar across the disorders, a finding that may provide some insight into the general nature of personality pathology but may also suggest problems with discriminant validity. Third, it does not appear that considering disorders as special combinations of features (as might be expected in some categorical models) is more informative than considering them as the sum of certain features (as might be expected in a dimensional model).

Adolescent↗
PubMed2000

Effectiveness of lateral slide exercise in an anterior cruciate ligament reconstruction rehabilitation home exercise program.

STUDY DESIGN: Two-group repeated measures design using a sample of convenience of subjects with anterior cruciate ligament (ACL) reconstructive surgery. OBJECTIVES: To determine the effect of incorporating one specific weight-bearing exercise (lateral slide exercise using a slide board) into an ACL reconstruction home exercise program. BACKGROUND: Reduced clinic visits have increased the importance of home exercise programs in knee ligament reconstruction rehabilitation. Few studies have been conducted to test the efficacy of specific exercises as part of a home-based treatment program on subjects who have undergone ACL reconstruction. METHODS AND MEASURES: Fourteen subjects who underwent patella tendon autograft reconstruction on one of their ACLs were studied. Testing consisted of the following 4 measurements: peak isometric knee extension torque, peak isometric knee flexion torque, maximum lateral step height, and lateral step-up repetitions to fatigue. Subjects were pretested at 8 weeks after surgery and were randomly placed into either a control or experimental group. The postsurgical rehabilitation was similar for both groups, except the experimental group incorporated lateral slide exercise into their home exercise program. All subjects were re-evaluated 14 weeks after surgery. RESULTS: A 2-way repeated measure ANOVA (group by test session), and posthoc testing revealed significant improvements in the slide group for quadricep strength (101.9 +/- 31.3 N m to 140.5 +/- 31.3 N m of torque), while the control group showed no significant increase (125.1 +/- 61.7 N m to 125.8 +/- 45.1 N m of torque). Lateral step height also improved in the slide group (from 22.9 +/- 5.3 cm to 28.7 +/- 5.6 cm), while the control group showed no increase (20.0 +/- 4.5 cm to 20.7 +/- 3.4 cm). Both groups increased in lateral step-up repetitions to fatigue. CONCLUSION: Including lateral slide exercise in a home exercise program after ACL reconstruction appears to improve knee extension strength.

Adult↗
PubMed1999

Sexual orientation and suicidality: a co-twin control study in adult men.

BACKGROUND: Several recent studies have found a higher lifetime prevalence of suicide attempts in homosexual males compared with heterosexual control subjects or population rates. These studies used either convenience samples, most without controls, or population-based samples in which confounding factors such as depression and substance abuse were not measured. METHODS: This study used twins from the population-based Vietnam Era Twin Registry, Hines, Ill. An analytic sample of 103 middle-aged male-male twin pairs from the registry was identified in which one member of the pair reported male sex partners after age 18 years while the other did not. Four lifetime symptoms of suicidality as measured by the Diagnostic Interview Schedule were analyzed: thoughts about death, wanting to die, thoughts about committing suicide, and attempted suicide. A composite measure of reporting at least one suicidality symptom was also assessed. RESULTS: Same-gender sexual orientation is significantly associated with each of the suicidality measures. Unadjusted matched-pair odds ratios follow: 2.4 (95% confidence interval [CI], 1.2 - 4.6) for thoughts about death; 4.4 (95% CI, 1.7 - 11.6) for wanted to die; 4.1 (95% CI, 2.1 - 8.2) for suicidal ideation; 6.5 (95% CI, 1.5 - 28.8) for attempted suicide; and 5.1 (95% CI, 2.4 - 10.9) for any of the suicidal symptoms. After adjustment for substance abuse and depressive symptoms (other than suicidality), all of the suicidality measures remain significantly associated with same-gender sexual orientation except for wanting to die (odds ratio, 2.5 [95% CI, 0.7 - 8.81). CONCLUSIONS: The substantially increased lifetime risk of suicidal behaviors in homosexual men is unlikely to be due solely to substance abuse or other psychiatric comorbidity. While the underlying causes of the suicidal behaviors remain unclear, future research needs to address the inadequacies in the measurement of both sexual orientation and suicidality in population-based samples.

Adult↗
PubMed1999

Effect of prosthetic titanium wear debris on mitogen-induced monocyte and lymphoid activation.

Wear debris generated by joint implant components has been reported to activate inflammatory and immune cells. Particulate debris derived from prosthetic material induces monocytes/macrophages, lymphocytes, synoviocytes, and fibroblasts to secrete cellular products, such as cytokines, which mediate inflammation. It has been speculated that degradation products impair the ability of inflammatory and immune cells to mount a protective response against noxious agents and infectious organisms by interfering with cell activation. Recent in vitro studies suggest that soluble metal ions inhibit T and B cell activation, but it is not known whether insoluble metal particles generated by prosthetic wear in tissue have the same effect. The purpose of the present study was to determine whether titanium wear debris retrieved from periprosthetic tissues surrounding a failed knee prosthesis suppresses activation of human monocytic and lymphoid cells. Peripheral blood monocytes and lymphocytes were incubated with the nonspecific activator pokeweed mitogen (PWM) in the presence or absence of titanium particles. Cell proliferative capacity and production of interleukins IL-1beta and IL-2 were determined as measures of activation. Titanium wear debris induced monocyte secretion of IL-1beta at levels comparable to those induced by PWM alone. In combination with PWM, titanium wear debris stimulated monocytes to secrete higher concentrations of IL-1beta than is stimulated by titanium itself or by PWM alone. Titanium wear debris did not activate lymphocytes, as indicated by marginal changes in DNA synthesis and IL-2 secretion, nor did it suppress the PWM-induced stimulation of DNA synthesis and IL-2 secretion. Our study suggests that nonspecific mitogen activators in spite of exposure to titanium wear debris can stimulate monocytic and lymphoid cells.

Biocompatible Materials↗
PubMed1999

Treatment of grade 3 anal intraepithelial neoplasia by complete anal mucosal excision without fecal diversion: report of a case.

PURPOSE: The aim of this study was to remove completely the risk of malignant transformation without permanent or temporary fecal diversion in a patient with extensive anal intraepithelial neoplasia. METHODS: All anal canal mucosa and the lowest 1.5 cm of rectal mucosa were excised and the adjacent rectal mucosa and submucosa advanced to the anal verge skin. RESULTS: The patient achieved normal continence within a month after the operation. Multiple anal canal biopsies at 12 months after the operation revealed normal rectal mucosa. CONCLUSIONS: Total anal mucosal excision offers a relatively simple means of removing the malignant risk of anal intraepithelial neoplasia without fecal diversion in selected patients.

Anus Neoplasms↗
PubMed1998

Expression of delayed toxicity and lethal mutations in the progeny of human cells surviving exposure to radiation and other environmental mutagens.

PURPOSE: Delayed expression of lethal mutations in the progeny of cells which survived a toxic insult was first shown for ionizing radiation and is one of the signs of induced genomic instability. The effect appears to be related to DNA strand breakage or repair but not to the physical break itself. To investigate this and the relationship of lethal mutations or delayed death to other instability endpoints, cultures of immortal but non-transformed human keratinocytes were exposed to a range of environmental mutagens or cytotoxic compounds with different DNA damaging properties. METHODS: Delayed expression of damage was assessed by scoring a number of endpoints in the progeny of cells which survived exposure and underwent at least 15 population doublings. Endpoints included delayed apoptosis, cloning efficiency of cells in 'healthy' colonies and expression of the apoptosis regulatory proteins bcl-2 and BAX. RESULTS: The results clearly linked expression of delayed lethal mutations with substances that induced DNA strand breaks. All these substances are known also to induce oxidative stress. The occurrence of delayed damage required a threshold level of toxicity in the initially exposed population, which was remarkably similar for all the effective substances except cadmium. Alkylating agents or microtubule poisons that do not permit repair of DNA damage did not cause any delayed death. CONCLUSION: It is concluded that delayed cell death may be caused by widespread radical damage to DNA which is either signalled, thereby inducing an apoptotic response, or (mis-)repaired yielding a weak or unstable genome. It is likely that the process may be an important factor in determining the long-term response of populations to 'sublethal' levels of environmental mutagens whose mechanism of action includes DNA strand breakage and repair.

Antineoplastic Agents↗
PubMed1998

Effects of Metformin on Collagen Glycation and Diastolic Dysfunction in Diabetic Myocardium.

BACKGROUND: Collagen accumulation in the myocardial interstitium of diabetic animals is considered to promote diastolic stiffness through advanced glycosylation. Because in vitro data suggest that metformin can modify glycosylation, this study was undertaken in a canine diabetic model 4 months in duration. METHODS AND RESULTS: Untreated diabetics (group II) and diabetics treated with metformin alone (group III) or with insulin (group IV) were compared in the basal state and during volume infusion. Basal hemoglobin A(1c), heart rate, aortic pressure, and ejection fraction were comparable. Left ventricular end-diastolic pressure was significantly increased in the untreated diabetics of group II, associated with a reduced end-diastolic volume. By contrast these parameters in the metformin-treated diabetics of group III were comparable with those in the normals of group I. Similarly in group IV end-diastolic volume was higher than that in group II, but filling pressure, although lower, was not significantly so. Calculation of left ventricular chamber stiffness in the basal state indicated a higher level for group II compared with controls and the treatment groups. During the systemic infusion of dextran, the untreated diabetics of group II had the largest end-diastolic pressure increase and the smallest rise of end-diastolic volume of the treatment groups, consistent with a significantly greater chamber stiffness. Myocardial collagen concentration was increased in group II with an interstitial distribution on morphological exam. Levels of collagen-linked advanced glycosylation end products isolated from the left ventricular were significantly greater in group II than in group I. Treatment with metformin prevented the increment observed in the untreated diabetic but had no effect on the elevated collagen concentration. CONCLUSIONS: Untreated diabetics exhibited increased diastolic chamber stiffness associated with collagen-linked glycation in myocardium compared with control animals. Chronic metformin use prevented the abnormalities of function and composition.

Journal Article↗