Biomedical subjects

Michael Bailey

Publications and source records attributed to Michael Bailey.

At least 19 recordsLinked to original sources

PubMed2006

Work disability in adults with cystic fibrosis and its relationship to quality of life.

UNLABELLED: With increasing numbers of cystic fibrosis (CF) patients surviving to adulthood, issues related to vocation inevitably arise and warrant specific attention. We examined the percentage of participants with CF currently working and explored risk factors for work disability among adults with CF. METHOD: We recruited 50 consecutive patients from an adult cystic fibrosis service. Demographic, employment history, illness severity indicators and CF-attributed work disability factors were evaluated. Demographic risk factors for work disability using the illness severity measures of FEV(1), S-K score, CRDQ, and recent hospitalisation as independent variables were determined. RESULTS: Factorial analysis of a disability index (DI) indicated no dependency on FEV(1) or S-K score, but dependency on quality of life indices (p<0.05), age (p<0.05) and hospital admission rate (p<0.05). Hours worked per week were dependent on quality of life (p<0.01) (mastery of disease domain), fewer hospital admissions (p<0.01) and age (p<0.05). Sixty-eight percent of the sample reported that CF resulted in significant impediments to employment. However, few had sought vocational guidance (6%). CONCLUSION: Determinants of workforce participation shows that hours worked and perceived disability are more dependent on mastery of disease, age, and time in hospital, than on clinical severity scores. Health professionals may assist productivity through career counselling or tailored programs.

Adult↗

PubMed2006

A prospective study of the diagnostic potential of the knee tunnel view radiograph in assessing anterior knee pain.

The aim of this comparative study was to examine the potential advantage of the tunnel view radiograph over a series of weight bearing antero-posterior (AP), lateral and skyline radiographs. The study population consisted of 240 subjects with knee pain aged 19 to 93 years. A total of 309 knees had a weight bearing AP in extension, lateral, skyline and tunnel view radiographs. Each radiograph was reported with respect to features related to osteoarthritis, modified from the Ahlback system. Each feature was assessed using the tunnel radiograph alone and then the AP, lateral and skyline views in combination without, and blind to, the information from the tunnel view. On the basis of Bowker's test, the tunnel view was more likely to pick up abnormal intercondylar notch and tibial spine osteophytes but not loose bodies. We conclude that the tunnel view is a valuable addition in the routine assessment of the knee joint in osteoarthritis but not for the diagnosis of loose bodies alone.

Adult↗

PubMed2006

Impact of statin therapy on clinical outcomes in chronic heart failure patients according to beta-blocker use: results of CIBIS II.

BACKGROUND: HMG-CoA reductase inhibitors (statins) are widely prescribed in patients with established systolic chronic heart failure (CHF). However, there is considerable controversy regarding their benefit in this setting. We therefore conducted a post-hoc analysis of outcomes according to statin use within the Second Cardiac Insufficiency Bisoprolol Study of the beta-blocker, bisoprolol, in NYHA classes III-IV systolic CHF patients (left ventricular ejection fraction <35%), receiving background ACE inhibitor and diuretics. METHODS: Analysis of clinical outcomes was performed according to baseline use of statins and subsequent randomisation to placebo or bisoprolol. Cumulative incidence curves for clinical events were constructed using the Kaplan-Meier method and tested for significance by log-rank statistic. Multivariate analysis was performed using the Cox proportional hazards regression model. RESULTS: Two hundred and twenty-six of 2,647 patients were receiving statins at baseline (8.5%). Patients were well-matched in the 4 study groups at baseline for gender, weight, NYHA class and LVEF, however statin/bisoprolol patients were significantly younger (p < 0.05). Statin use at baseline was associated with a significant survival benefit compared with no statin use (p < 0.005, hazard ratio [HR] = 0.60, 95% confidence interval [CI] = 0.39-0.94). This benefit remained after adjusting for other significant predictors of survival (p < 0.05, HR = 0.60, 95%CI = 0.39-0.94). A significant interaction effect was noted with bisoprolol, survival being greatest in the statin/bisoprolol group (p < 0.001, HR = 0.14, 95% CI = 0.03-0.60). Survival was 98.3% in the statin/bisoprolol group, 82.1% in the statin/placebo group, 87.2% in the no statin/bisoprolol group and 82.8% in the no statin/placebo group. The statin/bisoprolol group was also associated with fewer cardiovascular (p < 0.005) and sudden deaths (p < 0.0005) compared with other groups. CONCLUSIONS: Despite the post-hoc, non-randomised nature of this analysis, these observations suggest that statin use appears to be beneficial in CHF. Furthermore, there appears to be a favourable interaction between statins and beta-blockade within the Second Cardiac Insufficiency Bisoprolol Study cohort. Prospective studies of statins are required to definitively address the role of these agents in established CHF.

Adrenergic beta-Antagonists↗

PubMed2006

Sustained reduction in serious fall-related injuries in older people in hospital.

OBJECTIVE: To determine whether the rate of falls and associated serious injuries in a hospital aged care setting can be reduced using a multistrategy prevention approach. DESIGN, SETTING AND PARTICIPANTS: Three-year quality improvement project comparing data at baseline (2001) and at 2-year follow-up (2003) after interventions to reduce falls. All patients admitted to the Aged Care Services wards at Caulfield General Medical Centre, Melbourne, between January 2001 and December 2003 were included. INTERVENTIONS: Multistrategy approach phased in over 3 months from September 2001 and involving data gathering, risk screening with appropriate interventions, work practice changes, environmental and equipment changes, and staff education. MAIN OUTCOME MEASURES: Total number of falls; number of falls resulting in serious injuries (fractures, head injuries, death); staff compliance with the risk assessment. RESULTS: Over a 2-year period, there was a 19% reduction in the number of falls per 1000 occupied bed-days (OBDs) (12.5 v 10.1; P = 0.001) and a 77% reduction in the number of falls resulting in serious injuries per 1000 OBDs (0.73 v 0.17; P < 0.001). Staff compliance with completing the falls risk assessment tool increased from 42% to 70%, and 60% of staff indicated they had changed their work practices to prevent falls. CONCLUSION: A multistrategy falls prevention program in an aged care hospital setting produced a significant reduction in the number of falls and a marked reduction in serious fall-related injuries. Incorporating a falls prevention program into all levels of an organisation, as part of daily care, is crucial to the success and sustainability of falls prevention.

Accidental Falls↗

PubMed2006

The finished DNA sequence of human chromosome 12.

Human chromosome 12 contains more than 1,400 coding genes and 487 loci that have been directly implicated in human disease. The q arm of chromosome 12 contains one of the largest blocks of linkage disequilibrium found in the human genome. Here we present the finished sequence of human chromosome 12, which has been finished to high quality and spans approximately 132 megabases, representing approximately 4.5% of the human genome. Alignment of the human chromosome 12 sequence across vertebrates reveals the origin of individual segments in chicken, and a unique history of rearrangement through rodent and primate lineages. The rate of base substitutions in recent evolutionary history shows an overall slowing in hominids compared with primates and rodents.

Animals↗

PubMed2006

Cerebral radiation necrosis: incidence, outcomes, and risk factors with emphasis on radiation parameters and chemotherapy.

PURPOSE: To investigate radiation necrosis in patients treated for glioma in terms of incidence, outcomes, predictive and prognostic factors. METHODS AND MATERIALS: Records were reviewed for 426 patients followed up until death or for at least 3 years. Logistic regression analysis was performed to identify predictive and prognostic factors. Multivariate survival analysis was conducted using Cox proportional hazards regression. Separate analyses were performed for the subset of 352 patients who received a biologically effective dose (BED) > or =85.5 Gy2 (> or =45 Gy/25 fractions) who were at highest risk for radionecrosis. RESULTS: Twenty-one patients developed radionecrosis (4.9%). Actuarial incidence plateaued at 13.3% after 3 years. In the high-risk subset, radiation parameters confirmed as risk factors included total dose (p < 0.001), BED (p < 0.005), neuret (p < 0.001), fraction size (p = 0.028), and the product of total dose and fraction size (p = 0.001). No patient receiving a BED <96 Gy2 developed radionecrosis. Subsequent chemotherapy significantly increased the risk of cerebral necrosis (p = 0.001) even when adjusted for BED (odds ratio [OR], 5.8; 95% confidence interval [CI], 1.6-20.3) or length of follow-up (OR, 5.4; 95% CI, 1.5-19.3). Concurrent use of valproate appeared to delay the onset of necrosis (p = 0.013). The development of radionecrosis did not affect survival (p = 0.09). CONCLUSIONS: Cerebral necrosis is unlikely at doses below 50 Gy in 25 fractions. The risk increases significantly with increasing radiation dose, fraction size, and the subsequent administration of chemotherapy.

Adult↗

PubMed2006

Predictors of decline in renal function after lung transplantation.

BACKGROUND: Survival after lung transplantation has improved, but with the consequence that long-term toxicities of treatment are of growing importance. In particular, renal impairment is common, has many causes, and carries with it increased morbidity and mortality. METHODS: We retrospectively analyzed clinical and laboratory data of 136 patients who underwent lung and heart-lung transplantation at our institution between 1990 and 2004 inclusive. Using multivariate analysis we considered the impact of age, gender, pulmonary diagnosis, transplant type (single lung, double lung, heart-lung), hypertension, diabetes mellitus, cigarette smoking, current immunosuppression, duration of calcineurin inhibitor (CNI) exposure and pre-existing renal impairment on renal function. RESULTS: At transplantation, creatinine clearance (CrCl) for the patient population was 108 +/- 3.28 (mean +/- SEM) ml/min/1.73 m(2). At end of follow-up (6 +/- 0.32 years) there was a significant decline in glomerular filtration rate (GFR) to 56.7 +/- 1.78 ml/min/1.73 m(2) (p < 0.001). Five of 136 patients (3.7%) developed end-stage renal failure (ESRF). On multivariate analysis, factors most strongly associated with this decline included (in order of significance): CrCl at transplantation; pack-years of cigarette smoking; exposure to sirolimus (SLM); CNI exposure; and age at transplantation. The rate of decline in GFR was linked to CrCl and age at the time of transplantation. CONCLUSIONS: This analysis has demonstrated that patients with a lower baseline CrCl, older age at transplantation, and a smoking history are at high risk for rapid loss of renal function after transplantation. To best preserve kidney function, these patients should be targeted for aggressive risk factor modification as well as minimization of CNI exposure wherever possible.

Adolescent↗

PubMed2006

Potential food allergens in wine: double-blind, placebo-controlled trial and basophil activation analysis.

OBJECTIVE: Recent Australian and international legislation requires labeling of wines made by using the potentially allergenic food proteins casein, milk, egg white, or isinglass (fish-derived) where "there is a detectable residual processing aid." We investigated whether wines fined using these proteins or non-grape-derived tannins (tree-nut derived) can provoke significant clinical allergic reactions (anaphylaxis) in patients with confirmed immunoglobulin E-mediated relevant food allergy. METHODS: A double-blind, placebo-controlled trial was performed to determine whether allergic reactions followed consumption of Australian commercial wines fined using one or more of the legislation-targeted food proteins. In addition, allergenicity of a larger panel of these wines was evaluated by blood basophil activation. RESULTS: No anaphylaxis was induced by wine consumption. Three mild clinical reactions to protein-fined wine and two mild reactions to unfined wine occurred, but there was no statistically significant difference in reaction parameters between subject groups or between processing aids. No pattern of basophil activation correlated with wine type, processing aid, or subject group. CONCLUSION: Wines fined with egg white, isinglass, or non-grape-derived tannins present an extremely low risk of anaphylaxis to fish-, egg-, or peanut-allergic consumers. Although consumption of milk protein-fined wine did not induce anaphylaxis, there were insufficient subjects to determine statistically whether wines fined with milk proteins present a risk to the very rare milk-allergic consumers. In summary, the observed lack of anaphylaxis and basophil activation induced by wines made using the legislation-targeted food proteins according to good manufacturing practice suggests negligible residual food allergens in these wines.

Adult↗

PubMed2006

Correlation between Bankart and Hill-Sachs lesions in anterior shoulder dislocation.

BACKGROUND: Bankart lesions and Hill-Sachs lesions are commonly associated with anterior shoulder dislocations. The presence of Bankart lesion indicates the need for surgical repair. Magnetic resonance imaging (MRI) has been shown to be sensitive in detecting these two lesions. The aim of this study is to investigate the correlation between Bankart lesions and Hill-Sachs lesions on MRI for patients with traumatic anterior shoulder dislocations. METHODS: Between 2003 and 2005, 61 patients from Alfred and Sandringham Hospitals had an MRI as part of the investigation for traumatic anterior shoulder dislocations. The MRI scans were reviewed and subsequently confirmed by a radiologist to show the presence or absence of Bankart and Hill-Sachs lesions. The data were then analysed by a statistician. RESULTS: Although patients with one of these lesions were more than two-and-a-half times as likely to have the other, small study numbers precluded this result from achieving statistical significance. (odds ratio, 2.67 (0.83-8.61), P = 0.10). Younger age was a strong predictor of a recurrence of shoulder dislocation (odds ratio, 0.93 (0.89-0.98), P = 0.005). The presence of Bankart or Hill-Sachs lesions on MRI for the primary shoulder dislocation group was similar to the recurrent group (73% vs. 72% for Bankart lesion and 67% vs. 70% for Hill-Sachs lesion). CONCLUSION: There is a strong correlation between both lesions. This apparent trend can be useful in predicting the presence of a Bankart lesion when a Hill-Sachs lesion is identified on a plain radiograph. This study suggests the consideration of surgical repair after identification of a Hill-Sachs lesion on plain radiographs, especially for younger patients where the rate of re-dislocation is high.

Adolescent↗

PubMed2006

Timed Up and Go test is not useful as a discharge risk screening tool.

OBJECTIVE: To determine whether the 'Timed Up and Go' (TUG) test is a useful test for predicting re-attendance at an ED, emergency hospital admission or death within 90 days in elderly patients discharged from the ED. METHODS: This was a prospective blinded cohort study at a tertiary referral ED. Patients completed a TUG test during their Allied Health assessment prior to discharge from the department. After 90 days, patient ED attendances, emergency admissions to hospital or deaths were recorded and confirmed by phone. Data were analysed using logistic regression and reported as odds ratios (OR) or log-transformation and Pearson analysis. RESULTS: One hundred patients were enrolled: 78 (78%, 95% confidence interval [CI] 70-86%) patients remained event free, 22 (22%, 95% CI 14-30%) patients re-attended an ED and 15 (15%, 95% CI 8-22%) were admitted to hospital as an emergency admission. There was no significant difference between TUG test times and whether patients re-attended an ED (OR 1.0 [0.93-1.06] P = 0.9) or were admitted to hospital (OR 0.99 [0.91-1.07] P = 0.74). There was no significant correlation between a patient's TUG test time and the number of days to ED re-attendance (Pearson correlation coefficient 0.38 [-0.04 to 0.69] P = 0.08) or admission (Pearson correlation coefficient 0.32 [-0.23 to 0.71] P = 0.25). CONCLUSION: This study did not detect any predictive value of the TUG test for ED re-attendance or hospital admission within 90 days of discharge among aged ED patients.

Aged↗

PubMed2006

Investigation of the variables that impact upon the knowledge of cardiac risk factors.

OBJECTIVE: Awareness of cardiac disease risk factors is required before they can be modified. The present study aimed to investigate risk factor knowledge and the variables that impact upon this knowledge. METHODS: We undertook an analytical, cross-sectional survey of 226 patients attending an ED. Patients were asked to recall as many cardiac risk factors as possible and to rate the risk of nine given risk factors. Data relating to sources of risk factor information were collected. Uni- and multivariate (multiple linear regression) analyses determined variables that impacted upon the risk factor knowledge score. RESULTS: Mean patient age was 60.2 +/- 15 years, 55.3% (95% confidence interval 48.6-61.9) were male and 19.9% (95% confidence interval 15.0-25.8) had known cardiac disease. The mean risk factor knowledge score of 2.5 +/- 1.5 out of a possible 12 (median 3) was indicative of poor knowledge. Smoking, poor diet and stress/worry/tension were the most common factors reported. Variables impacting significantly on the knowledge score were English as a first language (P < 0.001), age (negative correlation, P < 0.001) and the receipt of information relating to cardiac health (P < 0.001). The patients' general practitioner and the media were the most important sources of information. CONCLUSIONS: Patients' knowledge of cardiac risk factors is generally poor and education strategies are indicated. At the individual level, the general practitioner is likely to remain as an important influence on knowledge. However, complementary media education programs are indicated at the community level. Patient subgroups at 'high risk' through poor knowledge should be specifically targeted.

Coronary Disease↗

PubMed2006

TRACP Influences Th1 pathways by affecting dendritic cell function.

UNLABELLED: TRACP, a marker of osteoclasts, is also expressed by cells of the immune system. We identified a novel function for TRACP in the dendritic cell. DCs from TRACP knockout mice have impaired maturation and trigger reduced Th1 responses in vivo. We postulate that TRACP has an important role in the presentation of antigens to T cells. INTRODUCTION: TRACP is highly expressed by osteoclasts, activated macrophages, and dendritic cells (DCs). Knockout mice lacking TRACP have an intrinsic defect in osteoclastic resorption and macrophages that display abnormal immunomodulatory responses and cytokine secretion profiles. Our aim in this study was to investigate the significance of TRACP in the inductive phase of the immune response by examining dendritic cells from TRACP(-/-) mice. MATERIALS AND METHODS: Maturational state and function of leukocyte subsets in mice was assessed by flow cytometry. The ability of the immune system to respond to nonspecific activation and to specific antigen was assessed by delayed type hypersensitivity and the presence of isotype-specific serum antibody in vivo and T-cell proliferation and cytokine production in vitro. RESULTS: The ability of lipopolysaccharide (LPS) to upregulate MHC II and CD80 in DCs from TRACP(-/-) mice was reduced compared with wildtype mice, although production of IL-10 by DCs from TRACP-deficient animals was increased. T- and B-cell responses not involving antigen presentation (anti-CD3, TNP-ficoll) were normal in TRACP(-/-) mice, but responses to T-dependent antigens were impaired. Specifically, TRACP(-/-) mice had defective delayed hypersensitivity responses to picryl chloride and reduced proliferative responses to ovalbumin compared with wildtype mice. In response to ovalbumin, but not anti-CD3, T cells from TRACP(-/-) mice produced less interferon-gamma (IFN-gamma), but there was no difference in IL-4 production: TRACP(-/-) mice also produced less ovalbumin (OVA)-specific IgG2a after immunization. CONCLUSIONS: The finding that DCs from TRACP(-/-) mice have impaired maturation and defective Th1 responses shows that TRACP is important for polarizing responses in naïve T cells to antigen-presented dendritic cells.

Acid Phosphatase↗

PubMed2005

Functional outcome of tibial plateau fractures treated with the fine-wire fixator.

OBJECTIVE: To review the functional outcome of patients with complex tibial plateau fractures treated with fine-wire fixation. DESIGN: Retrospective review with follow-up of patients in outpatient clinic. SETTING: Tertiary trauma center. PATIENTS: All patients who had fine-wire fixation for tibial plateau fractures between 1996 and January 2001 were reviewed. INTERVENTIONS: Fine-wire fixation with/without limited internal fixation for complex tibial plateau fractures. MAIN OUTCOME MEASURES: Knee range of motion, adequacy of articular surface reduction, mechanical axis, Knee Society Clinical Rating Scale and Short-Form 36 Health Questionnaire. RESULTS: Eighteen of twenty-one eligible patients were available for follow-up. There were 14 Shatzker VI and 4 V fractures. Seven fractures were open. Average follow-up was 28.2 months. All fractures united. There were three cases of delayed union, all progressed to union following additional procedures and bone grafting. There were no cases of osteomyelitis, septic arthritis or deep vein thrombosis. Seven patients had Knee Society Clinical Rating Scores of good/excellent (38.9%), and 11 had fair/poor scores (61.1%). Abnormal mechanical axes and multiple co-morbid injuries were associated with poorer outcomes. Although SF-36 scores were lower in the study group compared to matched population norms, 15 of 18 patients had full or partial return to pre-injury levels of functioning. CONCLUSION: Fine-wire fixation with limited internal fixation is a satisfactory method of managing complex high-energy fractures of the tibial plateau where soft tissue injury and bony comminution make traditional techniques of open reduction and internal fixation unsuitable.

Adult↗

PubMed2005

Early institution of mechanical support improves outcomes in primary cardiac allograft failure.

BACKGROUND: Primary graft failure (PGF) is the leading cause of early mortality after cardiac transplantation, accounting for 27.1% of deaths within 30 days. PGF is defined as severe dysfunction of the cardiac allograft without any obvious anatomic or immunological cause. The purpose of this study was to analyze our last 9 years of experience with cardiac transplantation to determine predictors of PGF and the influence on survival of our policy of early institution of mechanical circulatory support (MCS) in these patients. METHODS: Data on 214 consecutive cardiac transplants performed at The Alfred Hospital between January 1996 and August 2004 were reviewed. PGF was defined as right or left or biventricular failure manifesting as hypotension (systolic blood pressure <90 mm Hg), low cardiac output (cardiac index <2.0 liter/min/m2 and pulmonary capillary wedge pressure >20 mm Hg after coming off cardiopulmonary bypass despite inotropic support of up to 5 mug/min adrenaline and without any other obvious cause for the graft dysfunction. RESULTS: PGF developed in 51 patients (24%). Significant factors in the development of PGF were long ischemic time, which became significant over 4 hours (odds ratio, 1.43; p = 0.01) and increased donor age (odds ratio, 1.027; p = 0.045). Fifteen patients required mechanical support, and of these, 10 survived to leave hospital. CONCLUSIONS: PGF is the major cause of early mortality after cardiac transplantation. Significant risks for PGF are long allograft ischemic time and increased donor age. Once the patient has survived 30 days, however, the longer-term survival is not influenced by PGF. Our management strategy of early mechanical support has yielded good outcomes in this population with a high risk of early death.

Age Factors↗

PubMed2005

Body composition assessment in adults with cystic fibrosis: comparison of dual-energy X-ray absorptiometry with skinfolds and bioelectrical impedance analysis.

OBJECTIVE: We compared body composition measurement in adults with cystic fibrosis (CF) by using non-invasive methods (skinfold thicknesses and bioelectrical impedance analysis [BIA]) with dual-energy X-ray absorptiometry (DXA). METHODS: Seventy-six adults with CF (mean age 29.9 +/- 7.9 y, mean body mass index 21.5 +/- 2.5 kg/m(2)) were studied. Body composition was measured to calculate fat-free mass (FFM) using DXA, the sum of four skinfold thicknesses, and BIA (predictive equations of Lukaski and of Segal). RESULTS: Mean FFM values +/- standard deviation measured using DXA were 54.8 +/- 7.3 kg in men and 41.2 +/- 3.9 kg in women. Mean FFM values measured using BIA/Lukaski were 51.5 +/- 7.8 kg in men and 40.4 +/- 4.9 kg in women (P < 0.0005 for men, not significant for women for comparison with DXA). Mean FFM values measured using BIA/Segal were 54.2 +/- 7.5 kg for men and 44.1 +/- 5.9 kg for women (not significant for men, P < 0.0005 for women for comparison with DXA). Mean FFM values measured using skinfolds were significantly higher than those for FFM with DXA (57.2 +/- 7.2 kg in men, 43.3 +/- 4.3 kg in women, P < 0.0005 for comparison with DXA). The 95% limits of agreement with FFM using DXA were, for men and women, respectively, -8.3 to 1.7 kg and -6.4 to 4.8 kg for BIA/Lukaski, -4.8 to 3.6 kg and -3.1 to 8.9 kg for BIA/Segal, and -2.8 to 7.3 kg and -1.5 to 5.7 kg for skinfolds. CONCLUSION: This study suggests that skinfold thickness measurements and BIA will incorrectly estimate FFM in many adults with CF compared with DXA measurements of FFM. These methods have limited application in the assessment of body composition in individual adult patients with CF.

Absorptiometry, Photon↗

PubMed2005

Induction of humoral and CD8+ T cell responses are required for protection against lethal Ebola virus infection.

Ebola virus (EBOV)-like particles (eVLP), composed of the EBOV glycoprotein and matrix viral protein (VP)40 with a lipid membrane, are a highly efficacious method of immunization against EBOV infection. The exact requirements for immunity against EBOV infection are poorly defined at this time. The goal of this work was to determine the requirements for EBOV immunity following eVLP vaccination. Vaccination of BALB/c or C57BL/6 mice with eVLPs in conjunction with QS-21 adjuvant resulted in mixed IgG subclass responses, a Th1-like memory cytokine response, and protection from lethal EBOV challenge. Further, this vaccination schedule led to the generation of both CD4(+) and CD8(+) IFN-gamma(+) T cells recognizing specific peptides within glycoprotein and VP40. The transfer of both serum and splenocytes, but not serum or splenocytes alone, from eVLP-vaccinated mice conferred protection against lethal EBOV infection in these studies. B cells were required for eVLP-mediated immunity to EBOV because B cell-deficient mice vaccinated with eVLPs were not protected from lethal EBOV challenge. We also found that CD8(+), but not CD4(+), T cells are absolutely required for eVLP-mediated protection against EBOV infection. Further, eVLP-induced protective mechanisms were perforin-independent, but IFN-gamma-dependent. Taken together, both EBOV-specific humoral and cytotoxic CD8(+) T cell responses are critical to mediate protection against filoviruses following eVLP vaccination.

Adjuvants, Immunologic↗

PubMed2005

The isolation and characterisation of primary human laryngeal epithelial cells.

We have shown that the larynx has a prominent immunological component that varies between individuals, and which is influenced by lifestyle factors implicated in the pathogenesis of the inflammatory and neoplastic diseases of the larynx. In order to explore the mechanisms of such links between laryngeal mucosal immunity and the development of lifestyle-related disease, reliable in vitro models are essential. In this study, we isolated and characterised primary laryngeal epithelial cells from normal individuals and show they can be cultured and manipulated to express MHC class II molecules in vitro.

Cell Culture Techniques↗

PubMed2005

Protein production and induction of the unfolded protein response in Trichoderma reesei strain Rut-C30 and its transformant expressing endoglucanase I with a hydrophobic tag.

The effect of induction of protein production was studied in bioreactor cultures of T. reesei strain Rut-C30 and its transformant expressing endoglucanase I core domain (EGI, Cel7B) fused with a hydrophobic peptide tag. The tag was previously designed for efficient purification of the fusion protein in aqueous two-phase separation. The fungi were first grown on glucose-containing minimal medium after which rich medium with lactose as a carbon source was added to induce cellulase production. Production of extracellular protein and cellulase activity and the transcript levels of the major cellulase genes were analyzed during the cultivations. Induction of the cellulase genes followed a similar temporal pattern in both strains. The first phase of induction took place after addition of lactose as soon as glucose was depleted, and the second phase after lactose was consumed. Western analysis showed that a decreased amount of fusion protein was produced in the culture medium compared with the endogenous EGI, although the strain harbors several copies of the recombinant gene under the strong cbh1 promoter. The fusion protein appeared to accumulate within the cells, indicating impaired secretion of the protein. The mRNA levels of the UPR (unfolded protein response) target genes, bip1 and pdi1, and the level of the active form of hac1 transcript encoding the UPR transcription factor increased concurrently with induction of the cellulase genes in both strains, indicating increased requirement of the folding machinery under these conditions. However, only a minor increase in bip1 and pdi1 transcript level was observed in the transformant compared with the parental strain.

Bioreactors↗