Both CD4(+) and CD8(+) lymphocytes reduce the severity of tissue lesions in murine systemic candidiasis, and CD4(+) cells also demonstrate strain-specific immunopathological effects

The role of T lymphocytes in host responses to sublethal systemic infection with Candida albicans was evaluated by mAb depletion of CD4(+) and CD8(+) cells from BALB/c and CBA/CaH mice, which develop mild and severe tissue damage, respectively. Depletion of CD4(+) lymphocytes from BALB/c mice markedly increased tissue damage, but did not alter the course of infection. In CBA/CaH mice, depletion of CD4+ cells abrogated tissue destruction in both brain and kidney at day 4 after infection, and significantly decreased fungal colonization in the brain. However, the severity of tissue lesions increased relative to controls from day 8 onwards. A small increase in tissue damage was evident in both mouse strains after depletion of CD8(+) cells. There were no major differences between days 4 end 8 after infection in cDNA cytokine profiles of CD4(+) lymphocytes from either BALB/c or CBA/CaH mice. After passive transfer into infected syngeneic recipients, spleen cells from infected CBA/CaH mice markedly increased tissue damage when compared to controls, and also caused a significant increase in fungal colonization in the brain. A similar transfer in BALB/c mice increased the number of inflammatory cells in and around the lesions, but had no effect on the fungal burden in brain and kidney. The data demonstrate that both CD4(+) and CD8(+) lymphocytes contribute to the reduction of tissue damage after systemic infection with C. albicans, and that the development and expression of CD4(+) lymphocyte effector function is influenced by the genetic background of the mouse.

Evolution of the genetic covariance between male and female components of mate recognition: An experimental test

The evolution of a positive genetic correlation between male and female components of mate recognition systems will result as a consequence of assortative mating and, in particular, is central to a number of theories of sexual selection. Although the existence of such genetic correlations has been investigated in a number of taxa, it has yet to be shown that such correlations evolve and whether they may evolve as rapidly as suggested by sexual selection models. In this study, I used a hybridization experiment to disrupt natural mate recognition systems and then observed the subsequent evolutionary dynamics of the genetic correlation between male and female components for 56 generations in hybrids between Drosophila serrata and Drosophila birchii. The genetic correlation between male and female components evolved from 0.388 at generation 5 to 1.017 at generation 37 and then declined to -0.040 after a further 19 generations. These results indicated that the genetic basis of the mate recognition system in the hybrid populations evolved rapidly. The initial rapid increase in the genetic correlation was consistent with the classic assumption that male and female components will coevolve under sexual selection. The subsequent decline in genetic correlation may be attributable to the fixation of major genes or, alternatively, may be a result of a cyclic evolutionary change in mate recognition.

Assessment of limb muscle and adipose tissue by dual-energy X-ray absorptiometry using magnetic resonance imaging for comparison

OBJECTIVE: To use magnetic resonance imaging (MRI) to validate estimates of muscle and adipose tissue (AT) in lower limb sections obtained by dual-energy X-ray absorptiometry (DXA) modelling. DESIGN: MRI measurements were used as reference for validating limb muscle and AT estimates obtained by DXA models that assume fat-free soft tissue (FFST) comprised mainly muscle: model A accounted for bone hydration only; model B also applied constants for FFST in bone and skin and fat in muscle and AT; model C was as model B but allowing for variable fat in muscle and AT. SUBJECTS: Healthy men (n = 8) and women (n = 8), ages 41 - 62 y; mean (s.d.) body mass indices (BMIs) of 28.6 (5.4) kg/m(2) and 25.1 (5.4) kg/m2, respectively. MEASUREMENTS: MRI scans of the legs and whole body DXA scans were analysed for muscle and AT content of thigh (20 cm) and lower leg (10 cm) sections; 24 h creatinine excretion was measured. RESULTS: Model A overestimated thigh muscle volume (MRI mean, 2.3 l) substantially (bias 0.36 l), whereas model B underestimated it by only 2% (bias 0.045 l). Lower leg muscle (MRI mean, 0.6 l) was better predicted using model A (bias 0.04 l, 7% overestimate) than model B (bias 0.1 l, 17% underestimate). The 95% limits of agreement were high for these models (thigh,+/- 20%; lower leg,+/- 47%). Model C predictions were more discrepant than those of model B. There was generally less agreement between MRI and all DXA models for AT. Measurement variability was generally less for DXA measurements of FFST (coefficient of variation 0.7 - 1.8%) and fat (0.8 - 3.3%) than model B estimates of muscle (0.5-2.6%) and AT (3.3 - 6.8%), respectively. Despite strong relationships between them, muscle mass was overestimated by creatinine excretion with highly variable predictability. CONCLUSION: This study has shown the value of DXA models for assessment of muscle and AT in leg sections, but suggests the need to re-evaluate some of the assumptions upon which they are based.

Can tissue drug concentrations be monitored by microdialysis during or after isolated limb perfusion for melanoma treatment?

Isolated limb perfusion (ILP) with melphalan is used to treat recurrent melanoma. This study aimed to develop a microdialysis technique for melphalan tissue concentration measurement during ILP. The effects of melphalan concentration (50-600 mu g/ml), microdialysis flow rate (0.55-17.5 mu l/min), probe length (5-50 mm) and temperature (25-41.5 degrees C) on in vitro recovery were studied. In addition, in vivo recovery was measured in rat hindlimbs perfused with melphalan using 50 mm microdialysis probes implanted subcutaneously and into muscle. Both dialysate and tissue sample melphalan concentrations were determined by high performance liquid chromatography. The in vitro recovery of melphalan was not affected by melphalan concentration or temperature, but increased with probe length and decreased with flow rate. The melphalan concentrations in subcutaneous and muscle dialysates were not significantly different. A linear relationship was found between tissue dialysate concentrations and actual tissue concentrations of melphalan (r(2) = 0.97). Microdialysis is a potential method for tissue drug monitoring which may assist in the efficacious use of cytotoxics in human ILP. (C) 2000 Lippincott Williams & Wilkins.

The role of colour in signalling and male choice in the agamid lizard Ctenophorus ornatus

Bright coloration and complex visual displays are frequent and well described in many lizard families. Reflectance spectrometry which extends into the ultraviolet (UV) allows measurement of such coloration independent of our visual system. We examined the role of colour in signalling and mate choice in the agamid lizard Ctenophorus ornatus. We found that throat reflectance strongly contrasted against the granite background of the lizards' habitat. The throat may act as a signal via the head-bobbing and push-up displays of C. ornatus. Dorsal coloration provided camouflage against the granite background, particularly in females. C. ornatus was sexually dichromatic for all traits examined including throat UV reflectance which is beyond human visual perception. Female throats were highly variable in spectral reflectance and males preferred females with higher throat chroma between 370 and 400 nm. However, female throat UV chroma is strongly correlated to both throat brightness and chest UV chroma and males may choose females on a combination of these colour variables. There was no evidence that female throat or chest coloration was an indicator of female quality. However, female brightness significantly predicted a female's laying date and, thus, may signal receptivity. One function of visual display in this species appears to be intersexual signalling, resulting in male choice of females.

The effect of mammographic screening on invasive breast cancer in Western Australia

Objective: To determine whether mammographic screening has affected the presentation of invasive breast cancer in Western Australia. Design: Population-based reviews of the presentation of all invasive breast cancers diagnosed in Western Australia in 1989 and 1994. Setting: Western Australia (population 1.8 million), Active recruitment of women aged 50-69 years for mammographic screening began in 1989. Main outcome measures: Size and stage of invasive breast cancers at diagnosis. Results: From 1989 to 1994, the age-standardised incidence rose from 109 to 123 per 100 000 woman-years, based on 584 and 750 cases, respectively. The proportion of all invasive breast cancers detected as a result of a mammogram increased from 9.2% in 1989 to 34.5% in 1994. Among the cases where relevant information was recorded, the proportion of impalpable tumours increased from 7.7% in 1989 to 27.6% in 1994, and the average size of palpable tumours fell. There was an unexpected increase in the proportion of tumours that were negative on assays for oestrogen and progesterone receptors. Conclusions: A relatively simple and inexpensive clinical review has boosted confidence that the outlay of public monies required to establish and conduct screening in Australia appears likely to yield the reductions in mortality from breast cancer that would be predicted on the basis of the earlier controlled trials of mammography.

Differentiated dendritic cells expressing nuclear RelB are predominantly located in rheumatoid synovial tissue perivascular mononuclear cell aggregates

Objective. Differentiated dendritic cells (DC) and other antigen-presenting cells are characterized by the nuclear location of RelB, a member of the nuclear factor kappa B/Rel family. To characterize and enumerate differentiated DC in rheumatoid arthritis (RA) peripheral blood (PB), synovial fluid (SF), and synovial tissue (ST), the expression and location of RelB were examined. Methods. RelB protein expression and cellular location were determined in RA PB, SF, and ST by flow cytometry and immunohistochemical analysis of purified cells or formalin-fixed tissue. DNA-binding activity of RelB was determined by electrophoretic: mobility shift-Western immunoblotting assays. Results. Circulating RA PBDC resembled normal immature PBDC in that they did not express intracellular RelB protein. In RA ST serial sections, cells containing nuclear RelB (nRelB) were enriched in perivascular regions. A mean +/- SD of 84 +/- 10% of these cells were DC. The remaining nRelB+,HLA-DR+ cells comprised B cells and macrophages. Only 3% of sorted SFDC contained nRelB, However, RelB present in the nucleus of these SFDC was capable of binding DNA, and therefore capable of transcriptional activity. Conclusion. Circulating DC precursors differentiate and express RelB after entry into rheumatoid ST. Differentiated DC can thus be identified by immunohistochemistry in formalin-fixed ST. Signals for DC maturation may differ between RA ST and SF, resulting in nuclear location of RelB predominantly in ST. This is likely to have functional consequences for the DC in these sites.

Male Teachers in Feminised Teaching Areas: marching to the beat of the men's movement drums?

Calls for more male teachers are prevalent in current gender debates in education. A dominant argument in this debate is that boys are often alienated from school because of a lack of male role models in feminised areas of the school curriculum and in primary schools. Little research has investigated male teachers' accounts of their work within feminised environments. Drawing on data collected in two research studies in music education, this paper focuses on accounts given by male teachers about (a) practices adopted specifically to work with boys and (b) the role of the male music teacher. Analysis of these data suggests that some male teachers working in feminised areas of the school curriculum adopt practices which, rather than challenging dominant constructions of masculinity, sometimes reinforce gender stereotypical behaviours in boys. We argue that calls for increasing the number of male teachers in feminised areas of schooling need also to be informed by open discussion of the underlying assumptions about masculinity which teachers themselves bring to their work.

Early diagnosis of lymphedema in postsurgery breast cancer patients

Lymphedema is an accumulation of lymph fluid in the limb resulting from an insufficiency of the lymphatic system. It is commonly associated with surgical or radiotherapy treatment for breast cancer. As with many progressively debilitating disorders, the effectiveness of treatment is significantly improved by earlier intervention. Multiple frequency bioelectrical impedance analysis (MFBIA) previously was shown to provide accurate relative measures of lymphedema in the upper limb in patients after treatment for breast cancer, This presentation reports progress to date on a three-year prospective study to evaluate the efficacy of MFBIA to predict the early onset of lymphedema in breast cancer patients following treatment. Bioelectrical impedance measurements of each upper limb were recorded in a group of healthy control subjects (n = 50) to determine the ratio of extracellular limb-fluid volumes. From this population, the expected normal range of asymmetry (99.7% confidence) between the limbs was determined, Patients undergoing surgery to treat breast cancer were recruited into the study, and MFBIA measurements were recorded presurgery, at one month and three months after surgery, and then at two-month intervals for up to 24 months postsurgery, When patients had an MFBIA measure outside the 99.7% range of the control group, they were referred to their physician for clinical assessment. Results to date: Over 100 patients were recruited into the study over the past two years; at present, 19 have developed lymphedema and, of these, 12 are receiving treatment. In each of these 19 cases, MFBIA predicted the onset of the condition up to four months before it could be clinically diagnosed. The false-negative rate currently is zero, The study will continue to monitor patients over the remaining year to accurately ascertain estimates of specificity and sensitivity of the procedure.

Peroxisome proliferator-activated receptors in tumorigenesis: Targets of tumour promotion and treatment

The peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors. There are three genes that code for the PPAR isoforms: PPAR alpha, PPAR beta and PPAR gamma. In the present review, studies characterizing the various PPAR isoforms are discussed. Peroxisome proliferator-activated receptor alpha has been implicated in the lipid-lowering effects of the fibrate drugs. Peroxisome proliferator-activated receptor gamma has a clear role in adipocyte differentiation and is therapeutically targeted by the thiazolidinedione drugs for the treatment of type II diabetes. The physiological role of PPAR beta is less well understood but, as described in the present review, recent studies have implicated it with a role in colon cancer. In the present review, particular attention is focused on the role of PPAR in the regulation of expression of proteins associated with cell cycle control and tumorigenesis.

Absolute risk of breast cancer for Australian women with a family history

Background: The purpose of the present paper was to estimate the absolute risk of breast cancer over the remainder of a lifetime in Australian women with different categories of family history. Methods: Age-specific breast cancer incidence rates were adjusted for screening effects, and rates in those with no family history were estimated using the attributable fraction (AF). Relative risks from a published meta-analysis were applied to obtain incidence rates for different categories of family history, and age-specific incidence was converted to cumulative risk of breast cancer. The risk estimates were based upon Australian population statistics and published relative risks. Breast cancer incidence was from New South Wales women for 1996. The AF was calculated using prevalence of a family history of breast cancer from data on Queensland women. The cumulative absolute risk of breast cancer was calculated from decade and mid-decade ages to age 79 years, not adjusted for competing causes of death. Results: Lifetime risk is approximately 8.6% (1 in 12) for the general population and 7.8% (1 in 13) for those without a family history. Women with one relative affected have lifetime risks of 1 in 6-8 and those with two relatives affected have lifetime risks of 1 in 4-6. The cumulative residual lifetime risk decreases with advancing age; by age 60 years all groups with only one relative affected have well above a 90% probability of not developing breast cancer to age 79 years. Conclusions: These Australian risk statistics are useful for public information and in the clinical setting. Risks given here apply to women with average breast cancer risk from other risk factors.

Analysis of Mouse Keratin 6a Regulatory Sequences in Transgenic Mice Reveals Constitutive, Tissue-Specific Expression by a Keratin 6a Minigene

The analysis of keratin 6 expression is complicated by the presence of multiple isoforms that are expressed constitutively in a number of internal stratified epithelia, in palmoplantar epidermis, and in the companion cell layer of the hair follicle. In addition, keratin 6 expression is inducible in interfollicular epidermis and the outer root sheath of the follicle, in response to wounding stimuli, phorbol esters, or retinoic acid. In order to establish the critical regions involved in the regulation of keratin 6a (the dominant isoform in mice), we generated transgenic mice with two different-sized mouse keratin 6a constructs containing either 1.3 kb or 0.12 kb of 5' flanking sequence linked to the lacZ reporter gene. Both constructs also contained the first intron and the 3' flanking sequence of mouse keratin 6a. Ectopic expression of either transgene was not observed. Double-label immunofluorescence analyses demonstrated expression of the reporter gene in keratin 6 expressing tissues, including the hair follicle, tongue, footpad, and nail bed, showing that both transgenes retained keratinocyte-specific expression. Quantitative analysis of beta -galactosidase activity verified that both the 1.3 and 0.12 kb keratin 6a promoter constructs produced similar levels of the reporter. Notably, both constructs were constitutively expressed in the outer root sheath and interfollicular epidermis in the absence of any activating stimulus, suggesting that they lack the regulatory elements that normally silence transcription in these cells. This study has revealed that a keratin 6a minigene contains critical cis elements that mediate tissue-specific expression and that the elements regulating keratin 6 induction lie distal to the 1.3 kb promoter region.

Resident tissue macrophages within the normal rat iris lack immunosuppressive activity and are effective antigen-presenting cells

Despite extensive study of the numerous immunoregulatory mechanisms that contribute to the immune-privileged nature of the anterior chamber (AC) of the eye, little is known of the functional nature of antigen-presenting cells (APC) present in the tissues adjoining the AC. In the present study, we have compared the antigen-presenting capacity of dendritic cells (DC) and macrophages isolated from the normal rat iris. Whereas iris DC exhibited a potent ability to stimulate resting allogeneic T cells in MLR cultures (an in-vitro correlate of the ability to induce primary T cell responses), resident iris macrophages displayed negligible MLR-stimulatory capacity. Significantly, iris macrophages could efficiently elicit proliferation of primed antigen-specific T cells (an in-vitro correlate of the ability to act as local APC in secondary responses). This antigen-presenting activity was approximately half that of fully mature iris DC and considerably greater than that of freshly isolated iris DC. A key contributor to the effectiveness of resident iris macrophage antigen presentation was considered to be the absence of lymphocytostatic control of T cell proliferation exerted by these cells. The results indicate dichotomous but complementary roles for DC (immune surveillance) and macrophages (local antigen presentation in secondary responses) in this tissue.

Characterization of peroxisome proliferator-activated receptor alpha in normal rat mammary gland and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced mammary gland tumors from rats fed high and low fat diets

Normal Sprague-Dau ley rat mammary gland epithelial cells and mammary gland carcinomas induced by 2-amino-1 -methyl-6-phenylimidazo[4,5-b]pyridine, a carcinogen found in the diet, were examined for the expression of peroxisome proliferator-activated receptor alpha (PPAR alpha). PPAR alpha mRNA and protein was detected in normal and tumor tissue by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. By quantitative RT-PCR, carcinomas had a 12-fold higher expression than control mammary glands, a statistically significant difference. PPAR alpha expression was examined in carcinomas and normal tissues from rats on high fat (23.5/% corn oil) and low fat (5% corn oil) diets. Although neither carcinomas, nor control tissues showed statistically significant differences between the two diet groups, PPAR alpha expression was the highest in carcinomas from rats on the high fat diet. The expression of PPAR alpha in normal mammary gland and its significant elevation in mammary gland carcinomas raises the possibility of its involvement in mammary gland physiology and pathophysiology. (C) 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.