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C Bradbeer

Publications and source records attributed to C Bradbeer.

At least 19 recordsLinked to original sources
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↗
PubMed2000

Sequence changes in the ton box region of BtuB affect its transport activities and interaction with TonB protein.

Uptake of cobalamins by the transporter protein BtuB in the outer membrane of Escherichia coli requires the proton motive force and the transperiplasmic protein TonB. The Ton box sequence near the amino terminus of BtuB is conserved among all TonB-dependent transporters and is the only known site of mutations that confer a transport-defective phenotype which can be suppressed by certain substitutions at residue 160 in TonB. The crystallographic structures of the TonB-dependent transporter FhuA revealed that the region near the Ton box, which itself was not resolved, is exposed to the periplasmic space and undergoes an extensive shift in position upon binding of substrate. Site-directed disulfide bonding in intact cells has been used to show that the Ton box of BtuB and residues around position 160 of TonB approach each other in a highly oriented and specific manner to form BtuB-TonB heterodimers that are stimulated by the presence of transport substrate. Here, replacement of Ton box residues with proline or cysteine revealed that residue side chain recognition is not important for function, although replacement with proline at four of the seven Ton box positions impaired cobalamin transport. The defect in cobalamin utilization resulting from the L8P substitution was suppressed by cysteine substitutions in adjacent residues in BtuB or in TonB. This suppression did not restore active transport of cobalamins but may allow each transporter to function at most once. The uncoupled proline substitutions in BtuB markedly affected the pattern of disulfide bonding to TonB, both increasing the extent of cross-linking and shifting the pairs of residues that can be joined. Cross-linking of BtuB and TonB in the presence of the BtuB V10P substitution became independent of the presence of substrate, indicating an additional distortion of the exposure of the Ton box in the periplasmic space. TonB action thus requires a specific orientation for functional contact with the Ton box, and changes in the conformation of this region block transport by preventing substrate release and repeated transport cycles.

Bacterial Outer Membrane Proteins↗
PubMed2000

Women and HIV--revisited ten years on.

This article compares how women and their relationship to HIV has changed since the original publication of this article in 1990. The number of women infected with HIV has continued to rise, but, in contrast, there have been few changes in their management. We review transmission risks and manifestations of the infection, and also discuss the issues faced by women with HIV.

AIDS-Related Opportunistic Infections↗
PubMed1999

A new class of cobalamin transport mutants (btuF) provides genetic evidence for a periplasmic binding protein in Salmonella typhimurium.

No periplasmic binding protein has been demonstrated for the ATP-binding cassette (ABC)-type cobalamin transporter BtuCD. New mutations (btuF) are described that affect inner-membrane transport. The BtuF protein has a signal sequence and resembles the periplasmic binding proteins of several other ABC transporters.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1998

An exploration into occupational stress experienced by HIV health care professionals who work within genitourinary medicine settings.

The present study investigates the occupational stress of health care workers involved with HIV care in genitourinary medicine (GUM) outpatient departments. Sixteen nursing and 14 medical staff completed the P. Gray-Toft and J. G. Anderson (1981) occupational stress inventory. This assesses 7 potential sources of stress (death and dying, uncertainty regarding treatment, inadequate preparation, lack of support, conflict with others, conflict with physicians, and workload). The mean scores obtained revealed a preponderance of low-stress scores for both medical and nursing staff. Analyses of variance and covariance further demonstrated that, in general, levels of stress did not differ within or between the occupational groups. However, sources and characteristics of stress were different between nurses and doctors. In this group of health care professionals, their work with HIV-positive patients within the GUM outpatient setting may be instrumental in limiting levels of stress.

Adaptation, Psychological↗
PubMed1995

A technique for accurate use of CD4+ cell counts.

Despite uncertainty over their reliability, CD4+ cell counts are used extensively in both clinical and research settings to document progression in HIV infection. We examined, therefore, whether the performance of a simple statistical test would facilitate greater accuracy in the use of this marker. CD4+ cell count data were collected from a cohort of deceased (N = 60) and living HIV-positive gay men (N = 100). Pearson's product moment correlation coefficients were calculated for each individual in order to examine the association between CD4+ counts and time since diagnosis. Correlations of 0.7 or greater were obtained in approximately 50 percent of cases in each cohort. For these individuals, CD4+ cell counts were deemed to be a reliable indicator of rate of progression. The results suggest that the proposed technique ensures greater precision in the use of CD4+ cell counts and that the technique cna be used in individuals with either complete (deceased patients) or partial (living patients) CD4+ data.

CD4 Lymphocyte Count↗
PubMed1993

What is vestibular papillomatosis? A study of its prevalence, aetiology and natural history.

OBJECTIVES: To clarify the prevalence, aetiology, symptoms and natural history of vestibular papillomatosis. DESIGN: Study in two parts: 1. prevalence assessed by colposcopic examination of the vulva of unselected patients by one doctor (J.M.W.); 2. patients selected by clinical appearance as having vestibular papillomatosis (by J.M.W. and other doctors) assessed in a research clinic. SETTING: Outpatient genitourinary medicine clinic in South London. SUBJECTS: Part 1 study: 295 female clinic attenders; part 2 study: 18 women with clinical vestibular papillomatosis. MAIN OUTCOME MEASURES: Part 1 study: number of unselected patients found to have vestibular papillomatosis. Part 2 study: associated symptoms, histology, DNA hybridisation and polymerase chain reaction on vulval biopsies. Clinical regression of lesions. Cervical cytology and colposcopy. RESULTS: Part 1 study: Vestibular papillomatosis was identified by colposcopic examination of the vulva in 3/295 (1%) of women. Part 2 study: 9/18 (50%) women with vestibular papillomatosis were asymptomatic; the other nine had intermittent mild symptoms. Thirteen (72%) had a history of genital warts. Vulval biopsies had features suggestive of wart virus infection on histology in 17/18 (94%) and HPV16 was found by DNA hybridisation studies or polymerase chain reaction in 7/18 (39%). On follow up (mean duration 9 months) the vulval lesions had regressed in 9/12 patients. Ten patients had cervical wart virus infection or intraepithelial neoplasia (CIN), or both, and five needed laser treatment for this. CONCLUSIONS: In this study vestibular papillomatosis was associated with human papillomavirus (HPV) infection. This study suggests that vestibular papillomatosis need not be treated, but patients with it may be at increased risk for CIN.

Adolescent↗
PubMed1993

The proton motive force drives the outer membrane transport of cobalamin in Escherichia coli.

Cells of Escherichia coli pump cobalamin (vitamin B12) across their outer membranes into the periplasmic space, and it was concluded previously that this process is potentiated by the proton motive force of the inner membrane. The novelty of such an energy coupling mechanism and its relevance to other outer membrane transport processes have required confirmation of this conclusion by studies with cells in which cobalamin transport is limited to the outer membrane. Accordingly, I have examined the effects of cyanide and of 2,4-dinitrophenol on cobalamin uptake in btuC and atp mutants, which lack inner membrane cobalamin transport and the membrane-bound ATP synthase, respectively. Dinitrophenol eliminated cobalamin transport in all strains, but cyanide inhibited this process only in atp and btuC atp mutant cells, providing conclusive evidence that cobalamin transport across the outer membrane requires specifically the proton motive force of the inner membrane. The coupling of metabolic energy to outer membrane cobalamin transport requires the TonB protein and is stimulated by the ExbB protein. I show here that the tolQ gene product can partly replace the function of the ExbB protein. Cells with mutations in both exbB and tolQ had no measurable cobalamin transport and thus had a phenotype that was essentially the same as TonB-. I conclude that the ExbB protein is a normal component of the energy coupling system for the transport of cobalamin across the outer membrane.

2,4-Dinitrophenol↗