Prognostic significance of the bcl-2 apoptotic family of proteins in primary and recurrent cervical cancer

bcl-2 is one of a family of genes that control the apoptotic threshold of a cell. bcl-2 protein and its anti-apoptotic homologue, mcl-1, with the pro-apoptotic protein, bax, are thought to function by forming homo- and heterotypic dimers that then control the progression to apoptosis. p53 is also involved as a down-regulator of bcl-2 and a promoter of bax. To determine the effect of these apoptotic mechanisms, we used immunohistochemistry to determine the prognostic significance of the expression of bcl-2, mcl-1, bax and p53 in primary and recurrent cervical cancer. Tissues from 46 patients with primary cervical cancer and 28 women with recurrent carcinoma were stained for bcl-2, mcl-1, bax and p53. Kaplan-Meier survival analysis was performed using the log-rank test for differences between groups. In the primary disease group, positive staining for bcl-2 was associated with a better 5-year survival (bcl-2 +ve, 84% vs bcl-2 -ve, 53%, P = 0.03). Positive staining for p53 was associated with a survival disadvantage (p53 +ve, 4-year survival 38% vs p53 -ve, 4-year survival 78%, P = 0.02). mcl-1 and bax staining were not useful as prognostic indicators in primary disease. No marker was prognostic in recurrent disease. Positive bcl-2 staining defines a group of patients with primary disease with a good prognosis. p53, an activator of the bax promoter, identifies a group with a worse outcome. In recurrent disease, none of the markers reflected prognosis

Serum placental-type alkaline phosphatase activity in women with squamous and glandular malignancies of the reproductive tract

AIM -To investigate serum placental-type alkaline phosphatase (PLAP-type) activities in women with squamous and glandular malignancies of the reproductive tract using an immunoradiometric assay. METHODS--PLAP-type immunoreactivity was measured in 180 women with non-ovarian malignancies of the reproductive tract and the values were compared with those from 334 controls. The cases comprised 18 vulval, nine vaginal, 103 cervical, 46 endometrial, and five fallopian tube cancers. RESULTS - Serum PLAP-type activities were no different from controls in patients with squamous cell tumours. Women with adenocarcinoma of the cervix, endometrium, and fallopian tube had increased values: women with endometrial cancer had a median value nearly four times greater than that of controls. There was no direct correlation between PLAP-type activities and stage of disease in patients with endometrial cancer, but values reverted to normal after treatment. CONCLUSIONS -Serum PLAP-type measurements are of no value in the management of patients with squamous cell tumours of the female reproductive tract. Raised activities can, however, be found in glandular tumours, in particular endometrial cancer where serum PLAP-type measurements may be of value in predicting remission

The beta-subunit of human chorionic gonadotrophin exists as a homodimer

The free beta-subunit of human chorionic gonadotrophin (hCGbeta) is well recognised as a product of many epithelial tumours. Recently, it has been shown that this ectopic production may have a functional relationship to tumour growth. The growth-promoting activity of hCGbeta may be explained by its structural similarity to a family of growth factors which all contain the same distinct topological fold known as the cystine-knot motif. Since the other members of this family all exhibit their activities as homo- and heterodimers, it is possible that the same may be true for hCGbeta. Using size-exclusion chromatography, low stringency SDS-PAGE and matrix assisted laser desorption/ionisation (MALDI) time-of-flight (TOF) mass spectrometry (MS) we have shown that pure preparations of hCGbeta contain hCGbetabeta homodimers. Size-exclusion chromatography revealed asymmetric elution profiles with a forward peak corresponding to the size-exclusion characteristic of a globular protein with an approximate mass of 44-54 kDa and a late shoulder centered around an elution position expected for a globular protein of approximately 29 kDa. Two immunoreactive hCGbeta species, of approximately 32 and 64 kDa, were clearly resolved by SDS-PAGE and Western blotting. When analysed by MALDI-TOF MS a |mf23 kDa monomer and a |mf46 kDa dimer were identified. Formation of hCGbetabeta homodimers is consistent with the behaviour of other cystine-knot growth factors and strengthens the inclusion of the glycoprotein hormones within this superfamily. It has yet to be determined whether it is this dimeric molecular species that is responsible for growth-promoting activity of hCGbeta preparations in tumours

Prognostic significance of the bcl-2 apoptotic family of proteins in primary and recurrent cervical cancer.

bcl-2 is one of a family of genes that control the apoptotic threshold of a cell. bcl-2 protein and its anti-apoptotic homologue, mcl-1, with the pro-apoptotic protein, bax, are thought to function by forming homo- and heterotypic dimers that then control the progression to apoptosis. p53 is also involved as a down-regulator of bcl-2 and a promoter of bax. To determine the effect of these apoptotic mechanisms, we used immunohistochemistry to determine the prognostic significance of the expression of bcl-2, mcl-1, bax and p53 in primary and recurrent cervical cancer. Tissues from 46 patients with primary cervical cancer and 28 women with recurrent carcinoma were stained for bcl-2, mcl-1, bax and p53. Kaplan-Meier survival analysis was performed using the log-rank test for differences between groups. In the primary disease group, positive staining for bcl-2 was associated with a better 5-year survival (bcl-2 +ve, 84% vs bcl-2 -ve, 53%, P = 0.03). Positive staining for p53 was associated with a survival disadvantage (p53 +ve, 4-year survival 38% vs p53 -ve, 4-year survival 78%, P = 0.02). mcl-1 and bax staining were not useful as prognostic indicators in primary disease. No marker was prognostic in recurrent disease. Positive bcl-2 staining defines a group of patients with primary disease with a good prognosis. p53, an activator of the bax promoter, identifies a group with a worse outcome. In recurrent disease, none of the markers reflected prognosis

1000 Norms Project: Protocol of a cross-sectional study cataloging human variation

Background Clinical decision-making regarding diagnosis and management largely depends on comparison with healthy or ‘normal’ values. Physiotherapists and researchers therefore need access to robust patient-centred outcome measures and appropriate reference values. However there is a lack of high-quality reference data for many clinical measures. The aim of the 1000 Norms Project is to generate a freely accessible database of musculoskeletal and neurological reference values representative of the healthy population across the lifespan. Methods/design In 2012 the 1000 Norms Project Consortium defined the concept of ‘normal’, established a sampling strategy and selected measures based on clinical significance, psychometric properties and the need for reference data. Musculoskeletal and neurological items tapping the constructs of dexterity, balance, ambulation, joint range of motion, strength and power, endurance and motor planning will be collected in this cross-sectional study. Standardised questionnaires will evaluate quality of life, physical activity, and musculoskeletal health. Saliva DNA will be analysed for the ACTN3 genotype (‘gene for speed’). A volunteer cohort of 1000 participants aged 3 to 100 years will be recruited according to a set of self-reported health criteria. Descriptive statistics will be generated, creating tables of mean values and standard deviations stratified for age and gender. Quantile regression equations will be used to generate age charts and age-specific centile values. Discussion This project will be a powerful resource to assist physiotherapists and clinicians across all areas of healthcare to diagnose pathology, track disease progression and evaluate treatment response. This reference dataset will also contribute to the development of robust patient-centred clinical trial outcome measures

Computing environments for reproducibility: Capturing the 'Whole Tale'

The act of sharing scientific knowledge is rapidly evolving away from traditional articles and presentations to the delivery of executable objects that integrate the data and computational details (e.g., scripts and workflows) upon which the findings rely. This envisioned coupling of data and process is essential to advancing science but faces technical and institutional barriers. The Whole Tale project aims to address these barriers by connecting computational, data-intensive research efforts with the larger research process—transforming the knowledge discovery and dissemination process into one where data products are united with research articles to create “living publications” or tales. The Whole Tale focuses on the full spectrum of science, empowering users in the long tail of science, and power users with demands for access to big data and compute resources. We report here on the design, architecture, and implementation of the Whole Tale environment

Low Myo‐inositol indicating astrocytic damage in a case series of neuromyelitis optica

Astrocytic necrosis is a prominent pathological feature of neuromyelitis optica (NMO) lesions and is clinically relevant. We report 5 NMO‐related cases, all with longitudinally extensive lesions in the upper cervical cord, who underwent cervical cord 1H‐magnetic resonance spectroscopy. Lower myo‐inositol/creatine values, suggesting astrocytic damage, were consistently found within the NMO lesions when compared with healthy controls and patients with multiple sclerosis (MS), who showed at least 1 demyelinating lesion at the same cord level. Therefore, the in vivo quantification of myo‐inositol may distinguish NMO from MS. This is an important step toward developing imaging markers for clinical trials in NMO

Opportunities for improving irrigation efficiency with quantitative models, soil water sensors and wireless technology

Increasingly serious shortages of water make it imperative to improve the efficiency of irrigation in agriculture, horticulture and in the maintenance of urban landscapes. The main aim of the current review is to identify ways of meeting this objective. After reviewing current irrigation practices, discussion is centred on the sensitivity of crops to water deficit, the finding that growth of many crops is unaffected by considerable lowering of soil water content and, on this basis, the creation of improved means of irrigation scheduling. Subsequently, attention is focused on irrigation problems associated with spatial variability in soil water and the often slow infiltration of water into soil, especially the subsoil. As monitoring of soil water is important for estimating irrigation requirements, the attributes of the two main types of soil water sensors and their most appropriate uses are described. Attention is also drawn to the contribution of wireless technology to the transmission of sensor outputs. Rapid progress is being made in transmitting sensor data, obtained from different depths down the soil profile across irrigated areas, to a PC that processes the data and on this basis automatically commands irrigation equipment to deliver amounts of water, according to need, across the field. To help interpret sensor outputs, and for many other reasons, principles of water processes in the soil–plant system are incorporated into simulation models that are calibrated and tested in field experiments. Finally, it is emphasized that the relative importance of the factors discussed in this review to any particular situation varies enormously