Paper alert. Immunology.
A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in immunology.
Allergy and Immunology↗
Biomedical subjects
A Green
Publications and source records attributed to A Green.
Cigarette smoking and risk of epithelial ovarian cancer (Australia).
OBJECTIVES: We studied the association between cigarette smoking and ovarian cancer in a population-based case control study. METHODS: A total of 794 women with histologically confirmed epithelial ovarian cancer who were aged 18-79 years and resident in one of three Australian states were interviewed, together with 855 controls aged 18-79 years selected at random from the electoral roll from the same states. Information was obtained about cigarette smoking and other factors including age, parity, oral contraceptive use, and reproductive factors. We estimated the relative risk of ovarian cancer associated with cigarette smoking, accounting for histologic type, using multivariable logistic regression to adjust for confounding factors. RESULTS: Women who had ever smoked cigarettes were more likely to develop ovarian cancer than women who had never smoked (adjusted odds ratio (OR) = 1.5; 95% confidence interval (CI) = 1.2-1.9). Risk was greater for ovarian cancers of borderline malignancy (OR = 2.4; 95% CI = 1.4-4.1) than for invasive tumors (OR = 1.7; 95% CI = 1.2-2.4) and the histologic subtype most strongly associated overall was the mucinous subtype among both current smokers (OR = 3.2; 95% CI = 1.8-5.7) and past smokers (OR = 2.3; 95% CI = 1.3-3.9). CONCLUSIONS: These data extend recent findings and suggest that cigarette smoking is a risk factor for ovarian cancer, especially mucinous and borderline mucinous types. From a public health viewpoint, this is one of the few reports of a potentially avoidable risk factor for ovarian cancer.
Adenocarcinoma, Mucinous↗
Outcome of tyrosinaemia type III.
Tyrosinaemia type III is a rare disorder caused by a deficiency of 4-hydroxyphenylpyruvate dioxygenase, the second enzyme in the catabolic pathway of tyrosine. The majority of the nine previously reported patients have presented with neurological symptoms after the neonatal period, while others detected by neonatal screening have been asymptomatic. All have had normal liver and renal function and none has skin or eye abnormalities. A further four patients with tyrosinaemia type III are described. It is not clear whether a strict low tyrosine diet alters the natural history of tyrosinaemia type III, although there remains a suspicion that treatment may be important, at least in infancy.
4-Hydroxyphenylpyruvate Dioxygenase↗
Annexin-V imaging for noninvasive detection of cardiac allograft rejection.
Heart transplant rejection is characterized pathologically by myocyte necrosis and apoptosis associated with interstitial mononuclear cell infiltration. Any one of these components can be targeted for noninvasive detection of transplant rejection. During apoptotic cell death, phosphatidylserine, a phospholipid that is normally confined to the inner leaflet of cell membrane bilayer, gets exteriorized. Technetium-99m-labeled annexin-V, an endogenous protein that has high affinity for binding to phosphatidylserine, has been administered intravenously for noninvasive identification of apoptotic cell death. In the present study of 18 cardiac allograft recipients, 13 patients had negative and five had positive myocardial uptake of annexin. These latter five demonstrated at least moderate transplant rejection and caspase-3 staining, suggesting apoptosis in their biopsy specimens. This study reveals the clinical feasibility and safety of annexin-V imaging for noninvasive detection of transplant rejection by targeting cell membrane phospholipid alterations that are commonly associated with the process of apoptosis.
Adult↗
First experience of topical SDZ ASM 981 in children with atopic dermatitis.
BACKGROUND: SDZ ASM 981 is a selective inhibitor of inflammatory cytokine release under development for the topical treatment of atopic dermatitis. OBJECTIVES: This first paediatric study was designed to measure the systemic exposure to SDZ ASM 981 in young children with atopic dermatitis treated on extensive skin areas. METHODS: Children 1-4 years of age referred to a tertiary care centre for their atopic dermatitis were treated twice daily for 3 weeks with 1% SDZ ASM 981 cream. SDZ ASM 981 blood concentrations were measured on day 4 and 22 (last day) of treatment, and 1 week after the last application, using a radioimmunoassay with a limit of quantification of 0.5 ng mL(-1). Efficacy was assessed by the Eczema Area Severity Index (EASI). RESULTS: The 10 patients included had 23-69% of their body surface area (BSA) affected at baseline. Of the 63 SDZ ASM 981 blood concentrations measured, 63% were < 0.5 ng mL(-1); the maximum value observed was 1.8 ng mL-1. No accumulation was evidenced between days 4 and 22. The first two patients experienced a flare of atopic dermatitis that was not controlled by the study medication. In the other patients, the EASI improved by 8-89% at 3 weeks of treatment. CONCLUSIONS: In these children 1-4 years of age, blood concentrations of SDZ ASM 981 during topical treatment with the 1% cream were consistently low even in the children with the most extensive areas treated (up to 69% of their BSA).
Administration, Cutaneous↗
Association between epidermodysplasia verruciformis-associated human papillomavirus DNA in plucked eyebrow hair and solar keratoses.
Epidermodysplasia-verruciformis-associated human papillomavirus DNA has been demonstrated in squamous cell carcinomas and plucked hair from immunocompetent patients and renal transplant recipients. This study investigated the association between infection with epidermodysplasia-verruciformis-associated human papillomavirus, identified by the detection of viral DNA in plucked eyebrow hairs, and solar keratoses. These lesions are strongly predictive of squamous cell carcinoma. In a cross-sectional study 518 individuals were enrolled from a randomly selected sample of a subtropical Australian community. Epidermodysplasia-verruciformis-associated human papillomavirus DNA in eyebrow hair was detected using a nested polymerase chain reaction specific for epidermodysplasia-verruciformis-associated human papillomavirus types. Epidermo dysplasia-verruciformis-associated human papillomavirus DNA was present in 121 (49%) of 245 men and 116 (44%) of 262 women. There was a strongly significant increase in epidermodysplasia-verruciformis-associated human papillomavirus infection with age (p < 0.00001), with prevalences of 29% in the 25-39 y age group, 42% at 40-59 y and 65% in the 60-79 y age group. Among men there was a strong association between epidermodysplasia-verruciformis-associated human papillomavirus and solar keratoses with an odds ratio, adjusted for age, skin color, and occupational sun exposure, of 3.40 (95% confidence interval, 1.77-6.53). No such association was found among women [odds ratio 1.03 (95% confidence interval 0.59-1.77, after adjustment for the same factors)]. Differences in occupational sun exposure and smoking histories could not explain these apparently different associations between epidermodysplasia-verruciformis-associated human papillomavirus infection and solar keratoses in men and women. In conclusion, epidermodysplasia-verruciformis-associated human papillomavirus infection is associated with solar keratoses in men suggesting that epidermodysplasia-verruciformis-associated human papillomavirus infection, in conjunction with sex specific factors (like androgens), may be involved in neoplastic changes of keratinocytes.
Adult↗
Troglitazone is a competitive inhibitor of 3beta-hydroxysteroid dehydrogenase enzyme in the ovary.
OBJECTIVE: Troglitazone is a potent inhibitor of progesterone release from porcine granulosa cells. This is associated with a marked increase in pregnenolone secretion, implicating inhibition of the 3beta-hydroxysteroid dehydrogenase enzyme. This study determined whether troglitazone is a direct inhibitor of 3beta-hydroxysteroid dehydrogenase activity. STUDY DESIGN: Homogenates of porcine granulosa cells underwent classic enzyme kinetic analysis through Lineweaver-Burke and Dixon plotting. Human ovarian homogenates were also assayed for the effects of troglitazone on 3beta-hydroxysteroid dehydrogenase enzyme activity. Enzyme kinetics data were analyzed by the HyperKinetics software program. Analysis of variance was used to determine statistical significance for human ovarian homogenate experiments. RESULTS: In porcine granulosa cells Lineweaver-Burke analysis found that troglitazone inhibition of 3beta-hydroxysteroid dehydrogenase enzyme activity was competitive in nature, with 5 microg/mL troglitazone increasing the apparent Michaelis constant from 1.3 to 4.3 micromol/L (no change in maximum velocity). Dixon plot analysis demonstrated that the inhibition constant for troglitazone of 3beta-hydroxysteroid dehydrogenase is approximately 6.5 microg/mL, which is in the same order of magnitude as its therapeutic concentration in blood. Troglitazone also significantly decreased the activity of 3beta-hydroxysteroid dehydrogenase in homogenates of human ovarian tissue. CONCLUSION: We conclude that troglitazone can inhibit steroidogenesis in the ovary by direct competitive inhibition of 3beta-hydroxysteroid dehydrogenase.
3-Hydroxysteroid Dehydrogenases↗
The clinical utility of the Beck Depression Inventory after traumatic brain injury.
PRIMARY OBJECTIVE: To examine the psychometric properties of the Beck Depression Inventory (BDI) in traumatic brain injury (TBI) and to determine the relative endorsement of somatic-performance and cognitive-affective items in this group. RESEARCH DESIGN: Prospective 2 year follow up assessment. METHODS: 117 patients discharged from an inpatient TBI rehabilitation service completed the BDI as part of a 24 month follow up assessment. Demographic and injury related data were obtained from patient files and significant others. MAIN OUTCOMES: A principal components analysis revealed three factors describing affective and performance items, negative attitudes towards oneself and somatic disturbance. The reliability estimate was high (coefficient alpha = 0.92). A dependent sample t-test revealed higher endorsement of the cognitive-affective subscale with more clients classified as at least moderately depressed using the cognitive-affective rather than the total BDI score. CONCLUSION: This study provides preliminary evidence suggesting that the BDI may be an effective screening tool for self reported depression in TBI.
Adult↗
Polymorphisms at the glutathione S-transferase GSTM1, GSTT1 and GSTP1 loci: risk of ovarian cancer by histological subtype.
The phase II glutathione S-transferases (GSTs) GSTT1, GSTM1 and GSTP1 catalyse glutathione-mediated reduction of exogenous and endogenous electrophiles. These GSTs have broad and overlapping substrate specificities and it has been hypothesized that allelic variants associated with less effective detoxification of potential carcinogens may confer an increased susceptibility to cancer. To assess the role of GST gene variants in ovarian cancer development, we screened 285 epithelial ovarian cancer cases and 299 unaffected controls for the GSTT1 deletion (null) variant, the GSTM1 deletion (null) variant and the GSTP1 codon 104 A-->G Ile-->Val amino acid substitution variant. The frequencies of the GSTT1, GSTM1 and GSTP1 polymorphic variants did not vary with tumour behaviour (low malignant potential or invasive) or p53 immunohistochemical status. There was a suggestion that ovarian cancers of the endometrioid or clear cell histological subtype had a higher frequency of the GSTT1 and GSTM1 deletion genotype than other histological subgroups. The GSTT1, GSTM1 and GSTP1 genotype distributions did not differ significantly between unaffected controls and ovarian cancer cases (overall or invasive cancers only). However, the GSTM1 null genotype was associated with increased risk of endometrioid/clear cell invasive cancer [age-adjusted OR (95% CI) = 2.04 (1.01-4.09), P = 0.05], suggesting that deletion of GSTM1 may increase the risk of ovarian cancer of these histological subtypes specifically. This marginally significant finding will require verification by independent studies.
Adenocarcinoma, Clear Cell↗
No significant association between progesterone receptor exon 4 Val660Leu G/T polymorphism and risk of ovarian cancer.
Epidemiological studies suggest that ovarian cancer is an endocrine-related tumour, and progesterone exposure specifically may decrease the risk of ovarian cancer. To assess whether the progesterone receptor (PR) exon 4 valine to leucine amino acid variant is associated with specific tumour characteristics or with overall risk of ovarian cancer, we examined 551 cases of epithelial ovarian cancer and 298 unaffected controls for the underlying G-->T nucleotide substitution polymorphism. Stratification of the ovarian cancer cases according to tumour behaviour (low malignant potential or invasive), histology, grade or stage failed to reveal any heterogeneity with respect to the genotype defined by the PR exon 4 polymorphism. Furthermore, the genotype distribution did not differ significantly between ovarian cancer cases and unaffected controls. Compared with the GG genotype, the age-adjusted odds ratio (95% confidence interval) for risk of ovarian cancer was 0.78 (0.57-1.08) for the GT genotype, and 1.39 (0.47-4.14) for the TT genotype. In conclusion, the PR exon 4 codon 660 leucine variant encoded by the T allele does not appear to be associated with ovarian tumour behaviour, histology, stage or grade. This variant is also not associated with an increased risk of ovarian cancer, and is unlikely to be associated with a large decrease in ovarian cancer risk, although we cannot rule out a moderate inverse association between the GT genotype and ovarian cancer.
Base Sequence↗
Using costing as a district planning and management tool in Balochistan, Pakistan.
This paper reports on two studies in the province of Balochistan, Pakistan, analyzing the costs of primary care facilities and district and divisional hospitals. There are no known previous cost studies within Balochistan and the information gained is a critical element in developing a more rational allocation of resources within the health sector. The results demonstrate both the high level of under-funding of primary care within the health sector and the current inefficiency of allocation towards primary care and, within budgets, between different line items. Medicines in particular are significantly under-funded at the expense of staffing costs. The results are of use in developing more bottom-up budgeting systems within a more rational resource allocation system that is being developed as an element of the more decentralized health system towards which the province is working.
Budgets↗
Smoking and prostate cancer.
Explore the source record for details and available documents.
Epidemiologic Studies↗
Prejudice, social distance, and familiarity with mental illness.
In this study, the paths between two prejudicial attitudes (authoritarianism and benevolence) and a proxy measure of behavioral discrimination (social distance) were examined in a sample drawn from the general public. Moreover, the effects of two person variables (familiarity with mental illness and ethnicity) on prejudice were examined in the path analysis. One hundred fifty-one research participants completed measures of prejudice toward, social distance from, and familiarity with mental illness. Goodness-of-fit indexes from path analyses supported our hypotheses. Social distance is influenced by both kinds of prejudice: authoritarianism (the belief that persons with mental illness cannot care for themselves, so a paternalistic health system must do so) and benevolence (the belief that persons with mental illness are innocent and childlike). These forms of prejudice, in turn, are influenced by the believers' familiarity with mental illness and their ethnicity. We also discuss how these findings might contribute to a fuller understanding of mental illness stigma.
Adult↗
A study of infertility treatment and melanoma.
This study examined the possible association between melanoma and exposure to fertility drugs, specifically clomiphene citrate, human menopausal gonadotrophin (HMG) and human chorionic gonadotrophin (HCG). A cohort of 3186 women who attended a fertility clinic between 1 January 1980 and 31 December 1990 was studied; by January 1996, 14 women had been diagnosed with primary melanoma. Details of fertility treatment were extracted from the clinical records. The incidence of melanoma in the cohort resembled that of the female Queensland population (standardized incidence ratio = 0.89, 95% confidence interval [CI] = 0.54-1.48). Exposure to clomiphene citrate, HMG or HCG did not affect the incidence of melanoma. Women with infertile partners who were treated with fertility drugs were at increased risk of melanoma (odds ratio [OR] = 3.17, 95% CI = 1.01-9.98). Compared with women exposed only to clomiphene citrate and HMG, a lower incidence of melanoma was observed among those who received HCG as well (OR = 0.10, 95% CI = 0.02-0.42). Women exposed to two or more cycles of either clomiphene citrate (OR = 0.27, 95% CI = 0.08-0.94) or HMG (OR = 0.23, 95% CI = 0.07-0.84) had a significant reduction in melanoma risk compared with women exposed to no or one cycle. In summary, a woman's infertility per se was not found to be associated with melanoma, while exposure to fertility drugs was positively associated with melanoma in women with infertile partners and negatively associated in women with low doses of fertility drugs.
Adult↗
The clinical application of a dual head gamma camera with coincidence detection in 20 women with suspected ovarian cancer.
OBJECTIVE: To assess the effectiveness of a dual head coincidence gamma camera in identifying ovarian cancer as a less expensive alternative to the traditional 2-[18F] fluoro-2-deoxy-D-glucose (18FDG) system using positron emission tomography. DESIGN: Prospective study. POPULATION: Twenty consecutive women suspected of having ovarian carcinoma. Inclusion was based on abnormal serum CA125 (reference range is 0-35 units/L), ultrasound, computerised tomography or clinical findings. METHODS: Women underwent assessment before staging laparotomy. Two nuclear medicine physicians, who were blinded to the pre-operative assessment, reported on 18FDG- dual head coincidence gamma camera imaging. MAIN OUTCOME MEASURES: The histology and operative staging were compared with the 18FDG- dual head coincidence gamma camera findings. RESULTS: Twelve women had pelvic malignancies (nine primary and three recurrences), seven women had benign pathology and one patient had a borderline malignancy. We were able to image accurately all malignant pelvic masses with dual head coincidence gamma camera, as well as accurately demonstrate disease spread. Two of the benign pelvic masses localised 18FDG. The positive predictive value for detecting malignancy was 86%. CONCLUSIONS: Dual head coincidence gamma camera offers accurate and affordable imaging in suspected ovarian masses, with improved specificity over CA125, ultrasound and computerised tomography. These results are similar to those obtained on more expensive dedicated PET systems. We report on a series of patients believed to have primary or recurrent carcinoma and recognise the need to include patients more likely to have benign lesions to assess false positive results. However, we believe that dual head coincidence gamma camera is useful in the pre-operative assessment of women with suspected ovarian cancer.
Adult↗
The importance of genes and environment for ocular refraction and its determiners: a population based study among 20-45 year old twins.
AIMS: To estimate the heritability for ocular refraction and its determiners in a population based cohort of 20-45 years old twins. METHODS: 114 twin pairs (53 monozygotic and 61 dizygotic) participated. Refraction was determined in cycloplegia and eye dimensions were measured with ultrasound. Educational length was assessed. The heritability was estimated employing aetiological model fitting. Evidence of gene-environment interaction was analysed. Correlations between intrapairwise differences in educational length and in refraction were evaluated. RESULTS: The heritability was between 0.89 and 0.94 (95% CI: 0.82, 0.96) for refraction, total refraction, axial length, and radius of corneal curvature. Phenotypic variation was mostly due to additive genetic effects. Refraction revealed evidence of gene-environment interaction (r = -0.29 to -0.32; p <0.05). The heritability for anterior chamber depth and lens thickness was between 0.88 and 0.94 (95% CI: 0.81, 0.96) and dominant genetic effects were the most likely explanation. There was no correlation between age and intrapairwise differences in refraction. The dizygotic twins had significant larger intrapairwise differences in educational length (p <0.05), but the differences were not correlated with differences in refraction. CONCLUSIONS: The results indicate a high heritability for ocular refraction and its determiners and thus suggest that environmental impact on refraction is not significant. However, the epidemiological association between educational length (near work) and myopia, the evidence of increasing myopia prevalence within a few generations, and the theory of gene-environment interaction imply that some individuals might be genetically liable to develop myopia if exposed to certain environmental factors.
Adult↗
Familiarity with and social distance from people who have serious mental illness.
OBJECTIVES: This study examined the effects of familiarity with and social distance from persons who have serious mental illness on stigmatizing attitudes about mental illness. METHODS: A total of 208 community college students completed three written measures about familiarity, perception of dangerousness, fear, and social distance. Path analysis with manifest-variable structural modeling techniques was used to test a version of a model in which familiarity influences the perception of dangerousness, which in turn influences fear, which influences social distance from persons with serious mental illness. RESULTS: Most of the participants reported experience with mental illness. Scores on the three written measures largely supported the path model. Correlations between the perception of dangerousness and fear as well as between fear and social distance were particularly strong. CONCLUSIONS: Approaches to social change that increase the public's familiarity with serious mental illness will decrease stigma. Further studies are warranted that focus on how contact between members of the general public and persons who have serious mental illness may be facilitated.
Adult↗
Inhibition of proteasome activity blocks the ability of TNF alpha to down-regulate G(i) proteins and stimulate lipolysis.
Prolonged treatment of rat adipocytes with TNF alpha increases lipolysis through a mechanism mediated, in part, by down-regulation of inhibitory G proteins (G(i)). Separately, down-regulation of G(i) by prolonged treatment with an A(1)-adenosine receptor agonist, N(6)-phenylisopropyl adenosine (PIA) increases lipolysis. To investigate the role of proteolysis in TNF alpha and PIA-mediated G(i) down-regulation and stimulation of lipolysis, we used the protease inhibitors lactacystin (proteasome inhibitor) and calpeptin (calpain inhibitor). Rat adipocytes were preincubated for 1 h with lactacystin (10 microM) or calpeptin (50 microM), before 30-h treatment with either TNF alpha (50 ng/ml) or PIA (300 nM). We then measured lipolysis (glycerol release), abundance of alpha-subunits of G(i)1 and G(i)2 in plasma membranes (Western blotting) and protease activities (in specific fluorogenic assays). TNF alpha and PIA stimulated lipolysis approximately 2-fold and caused G(i) down-regulation. Although neither lactacystin nor calpeptin affected basal lipolysis, lactacystin completely inhibited both TNF alpha and PIA-stimulated lipolysis (the 50% inhibitory concentration was approximately 2 microM), whereas calpeptin had no effect. Similarly, lactacystin but not calpeptin blocked both PIA and TNF alpha-induced G(i) down-regulation. These findings provide further evidence that the chronic lipolytic effect of TNF alpha and PIA is secondary to G(i) down-regulation and suggest that the mechanism involves proteolytic degradation mediated through the proteasome pathway.
Acetylcysteine↗