Strain persistence of invasive Candida albicans in chronic hyperplastic candidosis that underwent malignant change

Objectives: The aim of this study was to assess persistence and tissue invasion of Candida albicans strains isolated from a 65 year‐old patient with chronic hyperplastic candidosis (CHC), that subsequently developed into squamous cell carcinoma (SCC). Materials and Methods: C. albicans (n=7) were recovered from the oral cavity of the patient over seven years. Confirmation of CHC and SCC in this patient was achieved by histopathological examination of incisional biopsy tissue. DNA fingerprinting was performed on the seven isolates from the CHC patient together with a further eight isolates from patients with normal oral mucosa (n=2), chronic atrophic candidosis (n=1), SCC (n=1) and CHC (n=4). Genotyping involved the use of inter‐repeat PCR using the eukaryotic repeat primer 1251. Characterisation of the tissue invasive abilities of the isolates was achieved by infecting a commercially available reconstituted human oral epithelium (RHE; SkinEthic, Nice, France). After 24 h. C. albicans tissue invasion was assessed by histopathological examination. Results: DNA fingerprinting demonstrated strain persistence of C. albicans in the CHC patient over a seven year period despite provision of systemic antifungal therapy. The strain of C. albicans isolated from this patient was categorised as a high invader within the RHE compared to other isolates. Conclusions: Candidal strain persistence was evident in a patient with CHC over seven years. This persistence may be due to incomplete eradication from the oral cavity following antifungal therapy or subsequent recolonisation from other body sites or separate exogenous sources. The demonstration of enhanced in vitro tissue invasion by this particular strain may, in part, explain the progression to carcinoma.     

Adaptation in the respiratory control system

Exposure to hypoxia, whether for short or prolonged periods or for repeated episodes, produces alterations in the ventilatory responses. This review presents evidence that these adaptations are likely to be mediated by adaptations in the respiratory chemoreflexes, particularly the peripheral chemoreflex, and proposes models of respiratory control explaining the observed changes in ventilation. After a brief introduction to the respiratory control system, a graphical model is developed that illustrates the operation of the system in the steady state, which will be used later. Next, the adaptations in ventilatory responses to hypoxia that have been observed are described, and methods of measuring the alterations in the chemoreflexes that might account for them are discussed. Finally, experimental data supporting the view that changes in the activity of the peripheral chemoreflex can account for the ventilatory adaptations to hypoxia are presented and incorporated into models of chemoreflex behaviour during exposures to hypoxia of various durations.     

Phylogenetic variation and polymorphism at the Toll-like receptor 4 locus (TLR4)

Background  

Differences in responses to bacterial surface lipopolysaccharides (LPSs) are apparent between and within mammalian species. It has been shown in mice that resistance to LPS is caused by defects in the Toll-like receptor 4 gene (Tlr4), the product of which is thought to bind LPS and mediate LPS signal transduction in immune system cells.     

Thresholds of potential concern as benchmarks in the management of African savannahs

In the Kruger National Park (KNP), South Africa, ecosystem managers use a series of monitoring endpoints, known as thresholds of potential concern (TPCs), to define the upper and the lower levels of accepted variation in ecosystems. For woody vegetation, the current TPC suggests that woody cover should not drop by more than 80% of its 'highest ever' value. In this paper, we explore the utility of palaeoecological data in informing TPCs. We use calibrated fossil pollen data to explore variability in vegetation at two sites over the past 5000 years, to provide a long-term record of changes in woody vegetation cover and a context for interpreting more recent vegetation change. The fossil pollen data are calibrated using studies of modern pollen and vegetation from KNP; arboreal pollen percentage was simulated using pollen-landscape modelling software for savannah landscapes of varying woody vegetation cover, and the relationship between vegetation and pollen data was quantified using nonlinear regression. This quadratic equation was then applied to fossil pollen data in order to estimate woody vegetation cover from arboreal pollen percentages. Our results suggest that the TPCs have not been exceeded during the period represented in the pollen record, because estimated woody vegetation cover has remained above 20% of its highest ever value. By comparing the fossil pollen data with TPCs, our study demonstrates how palaeoecological data can be presented in a form that is directly relevant to management objectives.     

Evolution of miniaturization and the phylogenetic position of <Emphasis Type="Italic">Paedocypris</Emphasis>, comprising the world's smallest vertebrate

Background  

Paedocypris, a highly developmentally truncated fish from peat swamp forests in Southeast Asia, comprises the world's smallest vertebrate. Although clearly a cyprinid fish, a hypothesis about its phylogenetic position among the subfamilies of this largest teleost family, with over 2400 species, does not exist. Here we present a phylogenetic analyses of 227 cypriniform taxa, including 213 cyprinids, based upon complete mitochondrial DNA cytochrome b nucleotide sequences in order to determine the phylogenetic position of Paedocypris and to study the evolution of miniaturization among cyprinids.     

An aid to the determination of the ventilatory threshold

Detection of the ventilatory threshold during an incremental load exercise test by eye can be difficult. Although various alternative methods employing information other than the ventilation can be used to assist in determining the ventilatory threshold, they rely on underlying assumptions about the physiological basis for the ventilatory threshold. The method presented here (CUSUM) uses only the ventilation data, and therefore avoids such assumptions. Twelve subjects performed a total of 47 incremental exercise tests to exhaustion. Determinations of the ventilatory thresholds made by eye from the ventilation data (mean of three independent observers) were used as a standard for comparison with determinations using the modified V-slope method and the CUSUM method. A mean (SD) difference of 0.6 (2.84) ml·min^–1·kg^–1 was found between the standard ventilatory thresholds and those determined using the modified V-slope method. A similar comparison between the standard ventilatory thresholds and those determined using the CUSUM method yielded a difference of –0.11 (2.35) ml min^–1·kg^–1. It was concluded that the CUSUM method was a useful aid for the detection of the ventilatory threshold using the ventilation data alone.     

Atypical clinical presentation of a subset of patients with anti-RNA polymerase III - non-scleroderma cases associated with dominant RNA polymerase i reactivity and nucleolar staining

Introduction

Anti-RNA polymerase III (RNAP III) antibodies are highly specific markers of scleroderma (systemic sclerosis, SSc) and associated with a rapidly progressing subset of SSc. The clinical presentation of anti-RNAP III positive patients, onset of Raynaud's phenomenon (RP) and SSc in unselected patients in a rheumatology clinic were evaluated.

Methods

Autoantibodies in sera from 1,966 unselected patients (including 434 systemic lupus erythematosus (SLE), 119 SSc, 85 polymyositis/dermatomyositis (PM/DM)) in a rheumatology clinic were screened by radioimmunoprecipitation. Anti-RNAP III positive sera were also tested by immunofluorescence antinuclear antibodies and anti-RNAP III ELISA. Medical records of anti-RNAP III positive patients were reviewed.

Results

Among 21 anti-RNAP III positive patients, 16 met the American College of Rheumatology (ACR) SSc criteria at the initial visit but 5 did not; diagnoses were vasculitis, early polyarthritis, renal failure with RP, interstitial lung disease, and Sjögren's syndrome. The first two patients developed rapidly progressive diffuse SSc. An additional case presented with diffuse scleroderma without RP and RP developed two years later. Anti-RNAP III antibodies in these 6 cases of atypical clinical presentation were compared with those in 15 cases of typical (SSc with RP) cases. Anti-RNAP III levels by ELISA were lower in the former group (P = 0.04 by Mann-Whitney test) and 3 of 6 were negative versus only 1 of 15 negative in the latter (P < 0.05 by Fisher's exact test). Three cases of non-SSc anti-RNAP III positive patients had predominant reactivity with RNAP I with weak RNAP III reactivity and had a strong nucleolar staining. Three anti-RNAP III patients, who did not have RP at the initial visit, developed RP months later. Scleroderma developed prior to RP in 5 out of 16 (31%) in the anti-RNAP III group, but this was rare in patients with other autoantibodies. The interval between the onset of RP to scleroderma was short in anti-RNAP III positive patients.

Conclusions

Anti-RNAP III antibodies are highly specific for SSc; however, a subset of anti-RNAP III positive patients do not present as typical SSc. The interval between RP and scleroderma in this group is short, and 31% of patients developed scleroderma prior to RP in this group. Anti-RNAP III positive patients may not present as typical SSc and detecting anti-RNAP III may have predictive value.