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Biomedical subjects

A Fowler

Publications and source records attributed to A Fowler.

At least 19 recordsLinked to original sources
PubMed2006

Community-acquired methicillin-resistant Staphylococcus aureus pyomyositis in an intravenous drug user.

Pyomyositis is a disease of abscess formation deep within large striated muscles. Outside of the tropics it is a rare disease which occurs mainly in certain patient populations such as the immunosuppressed or intravenous drug users (IDUs). A case of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) pyomyositis in an IDU is described. The incidence of both CA-MRSA and pyomyositis is currently increasing. To the authors' knowledge this is the first reported case of CA-MRSA pyomyositis in the UK. Cases of CA-MRSA pyomyositis are likely to increase and it may be necessary to empirically treat certain patients with glycopeptides.

Adult↗
PubMed2006

Multicentric Castleman's disease in HIV infection.

Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder. The precise incidence is unknown, although it is more common in HIV-positive than HIV-negative individuals. The pathological features of MCD strongly suggest a chronic antigen stimulation response, and human herpes virus 8 (HHV8) has been found to be universal in cases of HIV-related MCD. The presentation is non-specific with a wide differential diagnosis, which often results in a significant delay in its diagnosis. Diagnosis is made on the clinical presentation of a lymphoproliferative disorder, with evidence of multisystem involvement with classical histopathology on lymph node biopsy. Although no standard of care has been established for its treatment, symptomatic recurrences are often treated with corticosteroids and chemotherapy. The contribution of highly active antiretroviral treatment to the treatment of MCD remains debated. Novel treatments targeted at HHV8 show promising results, although evidence is currently limited to case reports. Randomized control trials assessing whether 'prophylactic' treatment with ganciclovir may prevent flares as currently used against cytomegalovirus disease in transplant patients are proposed. The prognosis of MCD in HIV-positive patients remains generally poor with a median survival of 48 months from diagnosis, and a 15-fold increased risk of non-Hodgkin's lymphoma.

Adult↗
PubMed2006

Multicentric Castleman's disease in a patient with HIV.

Multicentric Castleman's disease (MCD) was originally described in non-HIV patients. It is a rare lymphoproliferative disorder, which is more commonly seen in HIV-positive patients and is associated with human herpes virus-8 (HHV-8). We describe a patient with advanced HIV who responded well to conventional highly active antiretroviral treatment. She was diagnosed with MCD soon after her diagnosis of HIV. She presented with multiple flares of her MCD. The case illustrates the difficulty of differentiating between episodes of septicaemia and a flare of MCD. The patient was treated with various chemotherapy regimens, which included several cycles of liposomal doxyrubicin and etoposide. There is currently no consensus on the treatment of MCD and various therapies are described in the literature, which include chemotherapy. Chemotherapy must be chosen with the immunosuppressive effects of the treatment being considered with caution. Both doxyrubicin and etoposide are well tolerated and successfully controlled the symptoms of MCD in our patient.

Adult↗
PubMed2001

Beneficial effect of intracellular trehalose on the membrane integrity of dried mammalian cells.

Recently, there has been much interest in using trehalose and other small carbohydrates to preserve mammalian cells in the dried state as an alternative to cryopreservation. Here, we report on the successful preservation of plasma membrane integrity after drying, as a first step toward full preservation of mammalian cells. Trehalose was introduced into cells using a genetically engineered version of alpha-hemolysin, a pore-forming protein; the cells were then dried and stored for weeks at different temperatures with approximately 90% recovery of the intact plasma membrane. We show that protection of the plasma membrane by internal trehalose is dose dependent and estimate the amount of internal trehalose required for adequate protection to be approximately 10(10) molecules/cell. In addition, a minimal amount of water (approximately 15 wt%) appears to be necessary. These results show that a key component of mammalian cells can be preserved in a dried state for weeks under mild conditions (-20 degrees C and 5% relative humidity) and thereby suggest new approaches to preserving mammalian cells.

3T3 Cells↗
PubMed2001

Australian high-dose-rate brachytherapy protocols for gynaecological malignancy.

There is no consensus over the optimal dose fractionation schedules for high-dose-rate (HDR) brachytherapy used for gynaecological malignancy. In Australian public hospital departments of radiation oncology, HDR brachytherapy for gynaecological cancer is being more commonly used. A survey of public departments that are using this technology, or that plan to introduce this technology, was performed. Their current protocols are presented. In general, protocols are similar biologically; however, the practical aspects such as the number of fractions given do vary and may reflect resource restrictions or, alternatively, differences in interpretations of the literature and of the best protocols by clinicians.

Australia↗
PubMed2001

Genetic regulation of acquired immune responses to antigens of Mycobacterium tuberculosis: a study of twins in West Africa.

The role of genetic factors in clinical tuberculosis is increasingly recognized; how such factors regulate the immune response to Mycobacterium tuberculosis in healthy individuals is unclear. In this study of 255 adult twin pairs residing in The Gambia, West Africa, it is apparent that memory T-cell responses to secreted mycobacterial antigens (85-kDa antigen complex, "short-term culture filtrate," and peptides from the ESAT-6 protein), as well as to the 65-kDa heat shock protein, are subject to effective genetic regulation. The delayed hypersensitivity response to intradermal tuberculin also demonstrates significant genetic variance, while quantitative T-cell and antibody responses to the 38-kDa cell membrane protein appear to be determined largely by environmental factors. Such findings have implications for vaccine development.

Adolescent↗
PubMed2000

Literature review: supplemented phase diagram of the trehalose-water binary mixture.

Trehalose is of great interest in many fields, including freeze-drying, cryoprotection, and anhydrobiosis. Although data for the trehalose-water supplemented phase diagram have previously appeared in the literature, the data have been widely scattered and reported in several units. In this study, literature data for the binary trehalose-water system were collected and analyzed. The literature data were found to be reasonably consistent, with substantial agreement on the melting points for water, trehalose, and trehalose dihydrate and the glass transition temperature of water. There was also good agreement for the solubility, freezing, and glass transition curves. However, there was no general agreement on the glass transition temperature of pure trehalose. Additionally, the trehalose-water glass transition curve was modeled using the Gordon-Taylor equation, with a value for k of 5.2. The collected data in this report will be of much use in further studies of the protective abilities of trehalose.

Cryoprotective Agents↗
PubMed2000

Intracellular trehalose improves the survival of cryopreserved mammalian cells.

We report that the introduction of low concentrations of intracellular trehalose can greatly improve the survival of mammalian cells during cryopreservation. Using a genetically engineered mutant of Staphylococcus aureus alpha-hemolysin to create pores in the cellular membrane, we were able to load trehalose into cells. Low concentrations (0.2 M) of trehalose permitted long-term post-thaw survival of more than 80% of 3T3 fibroblasts and 70% of human keratinocytes. These results indicate that simplified and widely applicable freezing protocols may be possible using sugars as intracellular cryoprotective additives.

3T3 Cells↗
PubMed2000

Development of a high throughput scintillation proximity assay for hepatitis C virus NS3 protease that reduces the proportion of competitive inhibitors identified.

A screening assay has been developed for hepatitis C virus (HCV) NS3 protease using the scintillation proximity assay (SPA) technology. The sequence of the peptide substrate used was taken from the site cleaved by the enzyme in the mature nonstructural protein of HCV. The peptide was biotinylated at the N-terminus and tritiated at the C-terminus so that a decrease in signal was detected as a result of enzyme activity. IC(50) values were calculated for the cleaved product, and it was shown that the value obtained was dependent on the substrate concentration used. The effect of substrate concentration on the inhibition of HCV NS3 protease was further highlighted in a mock screening assay, using colored natural product samples, in which the hit rate was altered by a change in substrate concentration. An increase in substrate concentration reduced the proportion of competitive inhibitors identified. This study highlighted the importance of optimizing the components used in SPA assays in order to obtain an assay format valid for high throughput screening.

Binding, Competitive↗
PubMed2000

A multi-modality assay platform for ultra-high throughput screening.

The demand for increased throughput during primary screening using less reagents is changing the way of drug discovery. Searching for hits using high throughput screening in 96-well format plates is being replaced by the use of higher density plates, such as 384 and 1536-well formats. The analysis of radiometric assays by scintillation counters is becoming limiting since only 12 wells can be counted at a time. Charged coupled device (CCD) camera based instruments, that image the whole plate in one exposure, speed up detection and are compatible with any microplate footprint. Researchers are also demanding a choice of detection methods, including fluorescence, luminescence and radioactivity, and require imagers suitable for all applications. LEADseeker Homogenous Imaging System is a multi-modality platform offering imaging technology and assay toolboxes for radiometric, fluorescent and luminescent based assays. LEADseeker allows the very rapid analysis of high density formats enabling ultra-high throughput screening of a range of biological assays. Research areas that can be studied using this system include enzyme assays, receptor binding and molecular interactions.

Drug Design↗
PubMed1999

Characterization of the koala biovar of Chlamydia pneumoniae at four gene loci--ompAVD4, ompB, 16S rRNA, groESL spacer region.

Koalas are infected with two species of Chlamydia, C. pecorum and C. pneumoniae. While it is known that significant genetic diversity occurs in the C. pecorum strains infecting koalas, very little is known about the C. pneumoniae strains that infect this host. In the current study, 10 isolates of koala C. pneumoniae were analysed at four gene loci and found to be different to both the human and horse C. pneumoniae strains at all loci (biovar differences ranging from 0.3% at groESL up to 9.0% at ompAVD4). All koala biovar isolates studied were found to be 100% identical at ompAVD4 (all 10 isolates) and at ompB (all three isolates) gene. This lack of allelic polymorphisms at ompAVD4 has now been observed for koala C. pneumoniae, human C. pneumoniae, guinea pig inclusion conjuctivitis C. psittaci and feline conjuctivitis C. psittaci and may be correlated to a lack of antibody response to the chlamydial major outer membrane protein (MOMP) in these same strain/host combinations. This study also provides the first documented case of natural C. pneumoniae infection causing a severe and extended respiratory episode in a captive koala population. This captive episode is in contrast to most free-range observations in which koala C. pneumoniae is rarely documented as causing respiratory, ocular or urogenital tract disease.

Animals↗