Infectious Diseases - Research Publications
Permanent URI for this collection
Search Results
1 - 10 of 1253
-
ItemPI3K Activation in Neural Stem Cells Drives Tumorigenesis which can be Ameliorated by Targeting the cAMP Response Element Binding (CREB) Protein(Oxford University Press, 2018-10)BACKGROUND: Hyperactivation of phosphoinositide 3-kinase (PI3K) signaling is common in cancers, but the precise role of the pathway in glioma biology remains to be determined. Some understanding of PI3K signaling mechanisms in brain cancer comes from studies on neural stem/progenitor cells (NSPCs), where signals transmitted via the PI3K pathway cooperate with other intracellular pathways and downstream transcription factors to regulate critical cell functions. METHODS: To investigate the role of the PI3K pathway in glioma initiation and development, we generated a mouse model targeting the inducible expression of a PIK3CAH1047A oncogenic mutant and deletion of the PI3K negative regulator, phosphatase and tensin homolog (PTEN), to NSPCs. RESULTS: Expression of a Pik3caH1047A was sufficient to generate tumors with oligodendroglial features, but simultaneous loss of PTEN was required for the development of invasive, high-grade glioma. Pik3caH1047A-PTEN mutant NSPCs exhibited enhanced neurosphere formation which correlated with increased Wnt signaling, while loss of cAMP response element binding protein (CREB) in Pik3caH1047A-Pten mutant tumors led to longer symptom-free survival in mice. CONCLUSION: Taken together, our findings present a novel mouse model for glioma demonstrating that the PI3K pathway is important for initiation of tumorigenesis and that disruption of downstream CREB signaling attenuates tumor expansion.
-
ItemNo Preview AvailableCorrection: Does Malaria Affect Placental Development? Evidence from In Vitro Models(Public Library of Science (PLoS), 2013)
-
ItemNo Preview AvailableEvaluation of Haemophilus influenzae Type b Vaccine for Routine Immunization in Nepali Infants(Wolters Kluwer Health, 2012-04)BACKGROUND: Haemophilus influenzae type b (Hib) carriage and disease studies in Nepali children suggest a significant burden of infection. Hib conjugate vaccines (HibCV) do not have uniform immunogenicity between populations. We determined the immunogenicity of HibCV in Nepali infants, before its introduction into the routine immunization schedule. METHODS: Ninety infants recruited at Patan Hospital, Kathmandu, received 3 doses of the HibCV with routine immunizations (diphtheria, tetanus, whole cell pertussis-hepatitis B vaccine + oral polio vaccine) at 6, 10 and 14 weeks of age, and a HibCV booster at 52 weeks. Anti-polyribosylribitol phosphate (PRP) concentrations were measured at 18, 52 and 56 weeks, and the antibody persistence at 52 weeks was compared with antibody values in unimmunized controls (n = 30). RESULTS: After 3 doses of primary immunizations, at 18 weeks of age (n = 74), all infants had anti-PRP concentrations above the accepted thresholds for short- and long-term protection (0.15 and 1.0 µg/mL, respectively). At 1 year of age, before administration of the booster of HibCV, the anti-PRP geometric mean antibody concentration was 2.76 µg/mL (confidence interval: 1.88-4.07) in sera from the immunized children compared with 0.11 µg/mL (95% confidence interval: 0.08-0.17) in the nonimmunized control group (n = 30). Twenty-seven percent (20/74) of participants, however, had anti-PRP concentrations <1.0 µg/mL. Four weeks after the booster dose of HibCV, 98.5% of infants had anti-PRP concentrations above 1.0 µg/mL. CONCLUSION: Immunization with HibCV given as part of the Expanded Program on Immunization schedule in Nepal elicits robust antibody responses. Though the antibody wanes during the first year of life, most 1-year-old infants remain protected and respond robustly to a booster dose of the vaccine.
-
ItemNo Preview AvailableCerebral phaeohyphomycosis caused by Cladophialophora bantiana in a patient with chronic lymphocytic leukemia(Elsevier, 2006-07-15)The phaeohyphomycoses are infections caused by dematiaceous fungi. The dark pigmentation results from the melanin in their cell walls, which may be one of the factors responsible for the virulence and pathogenic potential of these fungi (1). Cladophialophora bantiana is highly neurotropic and accounts for the majority of cases of cerebral phaeohyphomycosis. Unlike many of the opportunistic fungi, most reported cases of cerebral phaeohyphomycosis caused by C. bantiana have occurred in immunocompetent patients. C. bantiana infection is often reported as being resistant to conventional medical therapy and as having an overall poor prognosis, regardless of immune status. Medical therapy is not standardized, and clinical experience with the newer azoles, such as voriconazole, has been limited.
-
ItemNo Preview AvailableBrain tumours in infancy: a clinicopathological study(Elsevier, 1997-04)To investigate the clinicopathological features of brain tumours occurring in the first year of life, the records of the Department of Histopathology at the Adelaide Children's Hospital were examined for cases where the initial diagnosis of intracranial neoplasm had been made in infancy. Surgical material was available for review from 1972 to 1993 and autopsy cases were reviewed for an additional 12 years from 1962 to 1993. Twenty-four infants with intracranial neoplasms were diagnosed ranging in age from 5 days to 1 year (average = 7 months). There were 23 surgical cases and 1 autopsy case. The male to female ratio was 17:7. Fifty-eight percent of the tumours were located in the supratentorial region. Although the incidence is relatively low, this study demonstrates that a wide range of brain tumours, which differ significantly in both clinical presentation and location from those found in the older child, do occur during the first year of life. The location of the primary tumour may be affected by associated congenital malformations, and metastatic malignancy, although rare, may occur. Antenatal ultrasound examination may be useful in identifying congenital intracranial tumours.
-
ItemImpact of chemically defined culture media formulations on extracellular vesicle production by amniotic epithelial cells(WILEY, 2021-07)The therapeutic properties of cell derived extracellular vesicles (EVs) make them promising cell-free alternative to regenerative medicine. However, clinical translation of this technology relies on the ability to manufacture EVs in a scalable, reproducible, and cGMP-compliant manner. To generate EVs in sufficient quantity, a critical step is the selection and development of culture media, where differences in formulation may influence the EV manufacturing process. In this study, we used human amniotic epithelial cells (hAECs) as a model system to explore the effect of different formulations of chemically defined, commercially sourced media on EV production. Here, we determined that cell viability and proliferation rate are not reliable quality indicators for EV manufacturing. The levels of tetraspanins and epitope makers of EVs were significantly impacted by culture media formulations. Mass spectrometry-based proteomic profiling revealed proteome composition of hAEC-EVs and the influence of media formulations on composition of EV proteome. This study has revealed critical aspects including cell viability and proliferation rate, EV yield, and tetraspanins, surface epitopes and proteome composition of EVs influenced by media formulations, and further insight into standardised EV production culture media that should be considered in clinical-grade scalable EV manufacture for generation of therapeutic EVs.
-
ItemAssessment of the cobas® HBV RNA investigational assay in the setting of nucleoside analog therapy cessation(WILEY, 2022-12)HBV RNA is used as a marker of cccDNA transcription and is applicable in the setting of nucleos(t)ide analog (NA) treatment, which suppresses HBV DNA. Traditional assays for quantification of HBV RNA rely on labor-intensive 3'RACE assays targeting the polyA tail. In this study, the high-throughput Roche cobas®HBV RNA investigational assay was assessed on the Roche cobas® 6800 automated platform. Of 969 samples collected for a NA treatment cessation trial, and tested on the cobas assay, 249 were analyzed for sensitivity, reproducibility, sample type applicability, and results were compared to a RACE-based assay. Results of 97 paired serum and plasma samples demonstrated an excellent correlation of 0.98. However, 14.5% of plasma samples yielded detectable (below the limit of quantification) results, when the paired serum was undetectable, and plasma was shown to yield a statistically significant (p < 0.001) greater mean 0.119 log10 copies/ml. Quantification of 152 samples showed good correlation (0.91) between the cobas and RACE assays. The cobas assay demonstrated superior lower limit of quantification, 10 copies/ml, which resulted in detection of 13.2% more samples than the RACE assay. Reproducibility and linear range of the automated assay were also confirmed. The Roche cobas assay for HBV RNA is sensitive and highly recommended.
-
ItemHealth services : knowledge, use and satisfaction of Afghan, Iranian and Iraqi settlers in Australia(Radcliffe Publishing, 2007)This paper reports the findings of a study examining the knowledge of, use of and satisfaction with local primary healthcare services reported by new arrivals to Australia from Iran, Iraq and Afghanistan. The study sample consisted of a purposive sample of 98 new settlers from the selected countries and used a semi-structured questionnaire and focus groups to attain information. Key findings were that friends and family were the greatest sources of health provider information and there was a lack of both more general health information and understanding of the health system. While study participants were able to access primary healthcare services and were generally satisfied, several major operational deficiencies were reported. General practitioners (GPs) were the major health providers for these groups. Health-seeking behaviours were strongly influenced by the country of birth in comparison with the other examined factors, and experiences of health service encounters also varied greatly between countries of birth. The facility’s proximity to the participant’s home was a strong influence in the selection of health services. The researchers recommend that a network of appropriately supported and staffed community health centres and/ or GP clinics is needed in areas where there are high concentrations of refugees and immigrants.
-
ItemNo Preview AvailableHealth issues in newly arrived African refugees attending general practice clinics in Melbourne(WILEY, 2006-12-04)OBJECTIVE: To identify the most common health issues diagnosed by general practitioners in newly arrived African refugees. DESIGN: Descriptive study based on a purposive sample of six GPs to collate data from medical records of patients from African countries who had attended their clinics for the first time between 1 January and 30 June 2005. SETTING: Two community health centres and two private general practices in metropolitan Melbourne. PARTICIPANTS: African refugee patients who arrived in Australia after 1 June 2004 and were seen by the six participating GPs between 1 January and 30 June 2005. MAIN OUTCOME MEASURES: Demographic characteristics, laboratory test results and final diagnoses. RESULTS: Data were collected from 258 patient files. Most patients were from Sudan (57%) or Liberia (17%). Half were aged under 15 years. The most common health problems identified were inadequate vaccinations, nutritional deficiencies (vitamin D and iron), infectious diseases (gastrointestinal infections, schistosomiasis, and latent tuberculosis) and dental disease. Musculoskeletal, psychological and social problems were common in adults. 37% of patients were tested for latent tuberculosis, and 25% of these tested positive. CONCLUSIONS: African refugees require comprehensive health assessments for undiagnosed and untreated health problems. While most of the common diseases identified are non-communicable, if left untreated they will affect the long-term health and productivity of new settlers.
-
ItemNo long-term evidence of hyporesponsiveness after use of pneumococcal conjugate vaccine in children previously immunized with pneumococcal polysaccharide vaccine(Elsevier, 2016-06)Background: A randomized controlled trial in Fiji examined the immunogenicity and effect on nasopharyngeal carriage after 0, 1, 2, or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar) in infancy followed by 23-valent pneumococcal polysaccharide vaccine (23vPPV; Pneumovax) at 12 months of age. At 18 months of age, children given 23vPPV exhibited immune hyporesponsiveness to a micro-23vPPV (20%) challenge dose in terms of serotype-specific IgG and opsonophagocytosis, while 23vPPV had no effect on vaccine-type carriage. Objective: This follow-up study examined the long-term effect of the 12-month 23vPPV dose by evaluating the immune response to 13-valent pneumococcal conjugate vaccine (PCV13) administration 4 to 5 years later. Methods: Blood samples from 194 children (now 5-7 years old) were taken before and 28 days after PCV13 booster immunization. Nasopharyngeal swabs were taken before PCV13 immunization. We measured levels of serotype-specific IgG to all 13 vaccine serotypes, opsonophagocytosis for 8 vaccine serotypes, and memory B-cell responses for 18 serotypes before and after PCV13 immunization. Results: Paired samples were obtained from 185 children. There were no significant differences in the serotype-specific IgG, opsonophagocytosis, or memory B-cell response at either time point between children who did or did not receive 23vPPV at 12 months of age. Nasopharyngeal carriage of PCV7 and 23vPPV serotypes was similar among the groups. Priming with 1, 2, or 3 PCV7 doses during infancy did not affect serotype-specific immunity or carriage. Conclusion: Immune hyporesponsiveness induced by 23vPPV in toddlers does not appear to be sustained among preschool children in this context and does not affect the pneumococcal carriage rate in this age group.