How to maintain an effectice research program

The discussion centered initially on the possibilities for and limitations of performing laboratory animal science research in the central animal units (CAU). Many such units are very small, often with only one or a few scientifically qualified member/s. It was agreed upon the necessity ofa minimum ”critical mass” of qualified people for the unit to be able to successfully conduct research and develop work within the field of laboratory animal science. It was pointed out, however, that it is necessary also for the small CAUs to get started, at whatever modest scale, to work and produce some publishable results, and thus slowly grow on their own merits. This was backed up by the firm belief that the laboratory animal scientistsshould be able/allowed to contribute to the advancement of knowledge. Implicit in this is that it is vital for the development of the CAUs to have resources e.g. space, for research of their own.Next to be discussed was the publication strategies within the CAUs. It was agreed upon that the scientific as well as the technical staff of the CAU could be co-authors on any publication arising as a result of work being done in the CAU. This  should, however, be based upon an active scientific contribution from the CAU member, such as being an active part in the planning of the experimental series and/or contributing actively to its conduct. It must be remembered that a CAU, from the point of view of scientists in general, is a service unit, similar to other kinds of service laboratories. Finally it was emphasised that the director of a CAU has considerable ethical obligations, covering all the work being done on animals in the unit. This could also mean that ”negative” results or problems arising in a particular project e.g. the modifying effect of an intercurrent infection on experimental results, might be turned into useful information for the field of laboratory animal science

Production of placental alkaline phosphatase (PLAP) and PLAP-like material by epithelial germ cell and non-germ cell tumours in vitro

Placental and placental-like alkaline phosphatase (PLAP) levels in the culture media of 87 cell lines of neoplastic and 'normal' origin were measured by a conventional immunosorbent enzymatic assay (IAEA) and by a new immunoradiometric assay (IRMA). The IRMA detected immunoreactive PLAP in 37 of 80 (46%) human epithelial and germ cell cultures, while the IAEA detected PLAP in only 25 (33%). Of the 52 non-germ cell tumour cultures, the IRMA detected expression in 24 (46%) and the IAEA in only 16 (31%). In 17 cases (21%) the IRMA recorded levels double that of the IAEA, while in five cultures (6%) the reverse was true. The IRMA was much more robust than the IAEA and had considerably lower inter- and intra-assay coefficients of variation (3.75-8.5% vs 5.2-46%). Detection of PLAP(-like) expression by IAEA is dependent on neoplastic expression of enzymatically functional molecules and quantification assumes constant enzyme kinetics. PLAP-like material has a higher catalytic rate constant than PLAP and thus will give higher values on a stoichiometric basis in an IAEA. The higher detection rate and levels of PLAP-like material in neoplastic cultures when measured by the IRMA clearly demonstrate ectopic expression of non-enzymatic PLAP and PLAP-like genes. The incidence of PLAP(-like) expression by non-germ cell and possible germ cell tumours has been underestimated and its utility as a tumour marker should be re-examined using assays which measure antigen mass rather than phosphatase activity

The effects of beta-human chorionic gonadotrophin on the in vitro growth of bladder cancer cell lines

The effects of human chorionic gonadotrophin (hCG) and its subunits on in vitro bladder cancer cell growth have been assessed using the a tetrazolium salt reduction assay (MTT). Intact hCG, alpha-hCG and beta-core hCG all had no effect on cell growth, while beta-hCG increased MTT reduction in all four bladder cancer lines tested. The magnitude of beta-hCG stimulation was maximal in the T24 line, which does not itself produce beta-hCG and appeared to be correspondingly lower in beta-hCG-secreting lines. The addition of antibodies to beta-hCG inhibited MTT reduction among high secretors but failed to inhibit MTT reduction in non-beta-hCG producers. These results are consistent with the poor prognosis associated with beta-hCG expression by bladder tumours in vivo and suggest an autocrine/paracrine stimulation of tumour growth by endogenously produced beta-hCG

The temporary anatomical structures prominent in the first trimester may be fulfilling exchange functions assigned to the placenta in the second and third trimester

The extra-embryonic coelom (EEC) and secondary yolk sac are prominent structures in the gestational sac during the first trimester of human pregnancy, at a time before the definitive placental circulation becomes established. We propose that the EEC and yolk sac play a critical role in the nutrition of early pregnancy, fulfilling exchange functions which are assumed by the placenta at a later stage

An update on the role of magnetic resonance imaging in predicting and monitoring multiple sclerosis progression

INTRODUCTION: While magnetic resonance imaging (MRI) is established in diagnosing and monitoring disease activity in multiple sclerosis (MS), its utility in predicting and monitoring disease progression is less clear. AREAS COVERED: The authors consider changing concepts in the phenotypic classification of MS, including progression independent of relapses; pathological processes underpinning progression; advances in MRI measures to assess them; how well MRI features explain and predict clinical outcomes, including models that assess disease effects on neural networks, and the potential role for machine learning. EXPERT OPINION: Relapsing-remitting and progressive MS have evolved from being viewed as mutually exclusive to having considerable overlap. Progression is likely the consequence of several pathological elements, each important in building more holistic prognostic models beyond conventional phenotypes. MRI is well placed to assess pathogenic processes underpinning progression, but we need to bridge the gap between MRI measures and clinical outcomes. Mapping pathological effects on specific neural networks may help and machine learning methods may be able to optimize predictive markers while identifying new, or previously overlooked, clinically relevant features. The ever-increasing ability to measure features on MRI raises the dilemma of what to measure and when, and the challenge of translating research methods into clinically useable tools

Expression of beta human chorionic gonadotrophin by non-trophoblastic non-endocrine 'normal' and malignant epithelial cells.

Expression of hCG and its free subunits by non-trophoblastic tumours is well recognised. Previously we reported hCG secretion by normal and malignant bladder epithelial cells in vitro. Here we examined culture medium from 83 different cell lines derived mainly from common epithelial tumours. Thirty-two of the cell lines were found to secrete hCG-like material into their culture media. Partial immunochemical characterisation showed that of these only choriocarcinoma and fetal tissue cell lines produced intact hCG and alpha subunit. The remaining 28 hCG-expressing epithelial cell lines, which are of mucosal origin, only secreted free beta subunit. Expression of free beta hCG by non-trophoblastic nonendocrine cells would appear to be especially characteristic of mucosal epithelia from the genitourinary and oral/respiratory tracts. Furthermore, this phenomenon may be characteristic of epithelium with transitional and/or squamous cell-like properties

Measurement of urinary beta core fragment of human chorionic gonadotrophin in women with vulvovaginal malignancy and its prognostic significance

Tumours of the vulva and vagina are rare and there are relatively few studies of circulating markers in these conditions. The urinary measurement of the core fragment of the beta-subunit of hCG has been proposed as a useful tumour marker in non-trophoblastic gynaecological malignancies. This study describe the measurement of urinary beta-core in 50 patients with vulvovaginal malignancy. In contrast to other studies corrections were made for both the effect of urine concentration and the age of the patient. Each patient was followed up for at least 24 months, and at this time their status was correlated with their initial level of urinary beta-core. The sensitivity of beta-core was only 38%, but of those patients with elevated levels 90% had died within 24 months, while only 32% of those with normal levels had died. For both patients at initial presentation and those with recurrent disease, there was a highly significant difference in the survival curve between those with elevated beta-core levels and those with normal levels. This is similar to findings in cervical carcinoma, and suggests that for lower genital tract cancer the measurement of urinary beta-core may be valuable as a prognostic indicator, allowing a more informed approach to treatment and follow-up

In vitro secretion of human chorionic gonadotrophin by bladder tumour cells.

Human chorionic gonadotrophin (hCG) and alphafetoprotein (AFP) were measured in culture media from a panel of 29 cell lines including 9 bladder carcinomas, 5 'normal' bladder epithelia, 10 germ cell tumours, and 5 miscellaneous tumours and 'normal' cell lines. In 7 of the 9 bladder carcinomas and 4 of the 5 'normal' bladder epithelia, the media contained hCG at levels ranging from between 34 and 3,600 IU l(-1). All other cell lines, including the 10 germ cell tumour lines gave negative results for hCG. These findings indicate that in vitro secretion of hCG is a common feature of normal and neoplastic bladder transitional epithelia, and support the hypothesis that parts of the genito-urinary epithelium have a potential for hCG production