Comparison of Immunologic Responses Between Mice Differing at the Agouti Locus : Immunologic Abnormalities in Lethal Yellow (Ay) Mice are Augmented by Obesity

The agouti locus, located on chromosome 2 of the house mouse (mus musclus), functions in the complex regulation of pigment synthesis. The complexity of its regulatory role is revealed through the aberrations that become manifest when a mutation, specifically the lethal yellow (AY) mutation, occurs at the agouti locus. The lethal yellow mutation is associated with an alteration in pigment synthesis, onset of obesity at approximately 120 days, and an increased susceptibility to cancer. Based on the putative relationship between cancer and immunity, this mutation may be correlated with altered immune mechanisms. This correlation was investigated by comparing a delayed-type hypersensitivity (DTH) response to dinitrofluorobenzene (DNFB), in vivo hormonal immunity to sheep red blood cell (SRBC), and in vitro lymphocyte reactivity of C57BL/6J Ay/a mice with congeneic a/a controls. Responses were compared between 42-day-old and 120-day-old mice to determine the correlation, if any, between altered immunity and age-onset obesity. Data indicate that the AY mutation is directly liked to a suppressed DIH response and, to some extent, a decreased reactivity to mitogen-induced lymphocyte proliferation. Obesity appears to play a role in the alteration in humoral immunity as demonstrated by an enhanced anti-SRBC IgM response and suppressed antibody-fanning cell (AFC) response to SRBC. Finally, serum from obese yellow (AY/a) mice was markedly suppressive in in vitro lymphocyte proliferation assays

Time for change: a new training programme for morpho-molecular pathologists?

The evolution of cellular pathology as a specialty has always been driven by technological developments and the clinical relevance of incorporating novel investigations into diagnostic practice. In recent years, the molecular characterisation of cancer has become of crucial relevance in patient treatment both for predictive testing and subclassification of certain tumours. Much of this has become possible due to the availability of next-generation sequencing technologies and the whole-genome sequencing of tumours is now being rolled out into clinical practice in England via the 100 000 Genome Project. The effective integration of cellular pathology reporting and genomic characterisation is crucial to ensure the morphological and genomic data are interpreted in the relevant context, though despite this, in many UK centres molecular testing is entirely detached from cellular pathology departments. The CM-Path initiative recognises there is a genomics knowledge and skills gap within cellular pathology that needs to be bridged through an upskilling of the current workforce and a redesign of pathology training. Bridging this gap will allow the development of an integrated 'morphomolecular pathology' specialty, which can maintain the relevance of cellular pathology at the centre of cancer patient management and allow the pathology community to continue to be a major influence in cancer discovery as well as playing a driving role in the delivery of precision medicine approaches. Here, several alternative models of pathology training, designed to address this challenge, are presented and appraised

A data processing module for acoustic doppler current meters

This report describes the development of a Data Processing Module (DPM) designed for use with an RD Instruments Acoustic Doppler Current Meter (ADCM). The DPM is a self-powered unit in its own pressure case and its use requires no modification to the current meter. The motivation for this work was the desire for real-time monitoring and data transmission from an ADCM deployed at a remote site. The DPM serves as an interface between the ADCM and a satellite telemetry package consisting of a controller, an Argos Platform Transmit Terminal, and an antenna. The DPM accepts the data stream from the ADCM, processes the data and sends out the processed data upon request from the telemetry controller. The output of the ADCM is processed by eliminating unnecessary data combining quality control information into a small number of summary parameters, and averaging the remaining data in depth and time. For the implementation described here, eight data records of 719 bytes each, output from the ADCM at 15 minute intervals, were processed and averged over 2 hr intervals to produce a 34 byte output array.Funding was provided by the Office of Naval Research under Contract No. N00014-89-J-1288

Caloric restriction alleviates abnormal locomotor activity and dopamine levels in the brain of the methionine sulfoxide reductase A knockout mouse

Oxidative stress is associated with the aging process, a risk factor for neurodegenerative diseases, and decreased by reduced energy intake. Oxidative modifications can affect protein function; the sulfur-containing amino acids, including methionine, are particularly susceptible to oxidation. A methionine sulfoxide can be enzymatically reduced by the methionine sulfoxide reductase (Msr) system. Previously, we have shown that MsrA−/− mice exhibit altered locomotor activity and brain dopamine levels as function of age. Previous studies have demonstrated that a caloric restriction enhances antioxidant defense and reduces the action of reactive oxygen species. Here we examine locomotor behavior and dopamine levels of MsrA−/− mice after caloric restriction starting at 8 months of age and ending at 17 months. The MsrA−/− mice did not have any significant difference in spontaneous distance traveled when compared to controls at 17 months of age. In contrast, our previous report showed decreased locomotor activity in the MsrA−/− mice at 12 months of age and older when fed ad-libitum. After completion of the caloric restriction diet, dopamine levels were comparable to control mice. This differs from the abnormal dopamine levels previously observed in MsrA−/− mice fed ad-libitum. Thus, caloric restriction had a neutralization effect on MsrA ablation. In summary, it is suggested that caloric restriction alleviates abnormal locomotor activity and dopamine levels in the brain of the methionine sulfoxide reductase A knockout mouse

Pathology and regulation for research in the UK: An overview [version 2; peer review: 3 approved]

The input of pathologists is essential for the conduct of many forms of research, including clinical trials. As the custodians of patient samples, pathology departments have a duty to ensure compliance with the relevant regulations, standards and guidelines to ensure the ethical and effective use for their intended investigational analysis, including when patients are participating in a research study. The results of research studies have impacts beyond the research study itself as they may inform changes in policy and practice or support the licensing of medicines and devices. Compliance with regulations and standards provides public assurance that the rights, safety and wellbeing of research participants are protected, that the data have been collected and processed to ensure their integrity and that the research will achieve its purpose. The requirements of the regulatory environment should not be seen as a barrier to research and should not significantly impact on the work of the laboratory once established and integrated into practice. This paper highlights important regulations, policy, standards and available guidance documents that apply to research involving NHS pathology departments and academic laboratories that are contributing to research involving human subjects

Pathology and regulation for research in the UK: An overview [version 2; peer review: 3 approved]

The input of pathologists is essential for the conduct of many forms of research, including clinical trials. As the custodians of patient samples, pathology departments have a duty to ensure compliance with the relevant regulations, standards and guidelines to ensure the ethical and effective use for their intended investigational analysis, including when patients are participating in a research study. The results of research studies have impacts beyond the research study itself as they may inform changes in policy and practice or support the licensing of medicines and devices. Compliance with regulations and standards provides public assurance that the rights, safety and wellbeing of research participants are protected, that the data have been collected and processed to ensure their integrity and that the research will achieve its purpose. The requirements of the regulatory environment should not be seen as a barrier to research and should not significantly impact on the work of the laboratory once established and integrated into practice. This paper highlights important regulations, policy, standards and available guidance documents that apply to research involving NHS pathology departments and academic laboratories that are contributing to research involving human subjects

Phototriggered Secretion of Membrane Compartmentalized Bioactive Agents

A strategy for the light-activated release of bioactive compounds (BODIPY, colchicine, paclitaxel, and methotrexate) from membrane-enclosed depots is described. We have found that membrane-permeable bioagents can be rendered membrane impermeable by covalent attachment to cobalamin (Cbl) through a photocleavable linker. These Cbl-bioagent conjugates are imprisoned within lipid-enclosed compartments in the dark, as exemplified by their retention in the interior of erythrocytes. Subsequent illumination drives the secretion of the bioactive species from red blood cells. Photorelease is triggered by wavelengths in the red, far-red, and near-IR regions, which can be pre-assigned by affixing a fluorophore with the desired excitation wavelength to the Cbl-bioagent conjugate. Pre-assigned wavelengths allow different biologically active compounds to be specifically and unambiguously photoreleased from common carriers

The Marine light - mixed layer experiment cruise and data report, R/V Endeavor : cruise EN-224, mooring deployment, 27 April-1 May 1991, cruise EN-227, mooring recovery, 5-23 September 1991

The Marine Light - Mixed Layer experiment took place in the sub-Arctic North Atlantic ocean, approximately 275 miles south of Reykjavik, Iceland. The field program included a central surface mooring to document the temporal evolution of physical, biological and optical properties. The surface mooring was deployed at approximately 59°N, 21°W on 29 April 1991 and recovered on 6 September 1991. The Upper Ocean Processes Group of the Woods Hole Oceanographic Institution was responsible for design, preparation, deployment, and recovery of the mooring. The Group's contrbution to the field measurements included four different types of sensors: a meteorological observation package on the surface buoy, a string of 15 temperature sensors along the mooring line, an acoustic Doppler current profiler, and four instruments for measuring mooring tension and accelerations. The observations obtained from the mooring are sufficient to describe the air-sea fluxes and the local physical response to surface forcing. The objective in the analysis phase will be to determine the factors controlling this physical response and to work towards an understanding of the links among physical, biological, and optical processes. This report describes the deployment and recovery of the mooring, the meteorological data, and the subsurface temperature and current data.Funding was provided by the Office of Naval Research under Contract N00014-89-J-1683

A primary health-care intervention on pre- and postnatal risk factor behavior to prevent childhood allergy. The Prevention of Allergy among Children in Trondheim (PACT) study

Background: This study aimed to evaluate the impact of a primary prevention intervention program on risk behavior for allergic diseases among children up to 2 years of age. The setting was in ordinary pre- and postnatal primary health care in Trondheim, Norway. Methods: The Prevention of Allergy among Children in Trondheim, Norway (PACT) study invited all pregnant women and parents to children up to 2 years of age in the community to participate in a non-randomized, controlled, multiple life-style intervention study. Interventional topics was increased dietary intake of cod liver oil and oily fish for women during pregnancy and for infants during the first 2 years of life, reduced parental smoking and reduced indoor dampness. A control cohort was established prior to the intervention cohort with “follow up as usual”. Questionnaires were completed in pregnancy, 6 weeks after birth and at 1 and 2 years of age. Trends in exposure and behavior are described. Results: Intake of oily fish and cod liver oil increased statistically significantly among women and infants in the intervention cohort compared to the control cohort. There was a low postnatal smoking prevalence in both cohorts, with a trend towards a decreasing smoking prevalence in the control cohort. There was no change in indoor dampness or in behavior related to non- intervened life-style factors. Conclusions: The dietary intervention seemed to be successful. The observed reduced smoking behavior could not be attributed to the intervention program, and the latter had no effect on indoor dampness