Stimulation of the greater occipital nerve increases metabolic activity in the trigeminal nucleus caudalis and cervical dorsal horn of the cat

The yeast Hansenula polymorpha is able to grow on vanadate concentrations that are toxic to other organisms. Transmission electron microscopy analysis showed that H. polymorpha cells growing on a vanadate-containing medium undergo a significant increase in cell vacuolation and a thickening of the cell wall; the presence of small cytoplasmic vesicles and an increase in cristae at the level of the plasma membrane were also observed. These ultrastructural modifications were accompanied by a change in the intracellular polyphosphate level, as shown by in vivo 31P-NMR. The involvement of these observed changes in vanadium detoxification is discussed.     

The cova programme for the validation of computer codes for fast reactor containment studies

The UKAEA and the Joint Research Centre, Euratom, Ispra are engaged in a collaborative experimental programme carrying out a series of small scale, well instrumented tests aimed at providing high quality data of the stresses, strains and loads occurring when a well characterized source is released within a fluid in a containment vessel. In the UK the data are being used to validate the computer codes ASTARTE and SEURBNUK which are used in studies of the response of the fast reactor primary containment system in the event of a hypothetical reactor excursion. This paper describes the UK experimental programme and the development of the low density explosive which is used as the energy source; the rationale of the code development programme is presented together with a report on the progress that has been made in validating the two codes against the experimental data.     

Cell biology and possible therapeutic applications of anti-CD3-activated killer-T cells (review)

Polyclonal T lymphocyte populations can be stimulated with anti-CD3 antibody to proliferate, secrete cytokines, and mediate MHC-unrestricted cytotoxic activity against a wide range of tumor target cells. Because anti-CD3-activated killer-T (AK-T) cells may be useful in the immunotherapy of human cancers, it is important to understand the signaling pathways and cell-surface structures involved in the induction and tumoricidal effector function of AK-T cells. Studies in the mouse model system have characterized the cytokines, signal transduction pathways, and costimulatory molecules involved in AK-T cell development. The recognition/adhesion and subsequent signaling events which lead to tumoricidal activity by mouse AK-T cells have also been defined. These findings, providing they translate accurately to the human system, may allow for the design of effective strategies to use AK-T cells for the treatment of human cancers. However, to date, the encouraging results obtained with anti-CD3 antibody/AK-T cell-based immunotherapies in mouse models of cancer have not been duplicated in clinical trials. The most likely explanation for this dis-appointing result is that tumor-reactive T lymphocytes in long term tumor-bearers fail to function correctly in the tumor microenvironment due to tumor-induced immune suppression and defects in key signal transduction molecules. It is clear that a detailed understanding of the inhibitory effect of established tumors on host T cells and the means to overcome tumor-induced immunosuppression are needed before anti-CD3 antibody/AK-T cell-based immunotherapies can be expected to succeed in the clinical setting.     

Effect of weaning age on growth,mammary gland development,and immune function in Holstein Friesian calves fed conserved alfalfa (FiberStart)

This study aimed to evaluate intake, body growth, and the development of the rumen, mammary gland, and immune system in Holstein Friesian calves reared for 100 d on the commercially available feed FiberStart (conserved alfalfa, Medicago sativa; Fiber Fresh Feeds Ltd., Reporoa, New Zealand) and fed calf milk replacer (CMR) for either 56 or 91 d. Eighty calves (40 bulls and 40 heifer calves) were reared indoors in groups (n = 5 of the same sex/pen). All calves were fed 4 L of CMR/d (175 g/L of CMR) in 2 feeds/d for the first 10 d and then 1 feed/d until d 49 or 84. The calves were gradually weaned by d 56 (earlier weaned; n = 8 pens) and d 91 (later weaned; n = 8 pens). All calves were fed FiberStart ad libitum as the only solid feed source from d 1 to 100 of the study. Irrespective of treatment, all calves had similar body weights at d 0 (40.9 ± 3.0 kg) and d 49 (74.2 ± 5.1 kg) of the study. Calf sex had no effect on intake, growth, blood, and immune system parameters. Earlier-weaned calves consumed 18% more solid feed dry matter but had 16% lower body weight gain (28.9 vs. 38.5 kg, respectively) from d 56 to 100 relative to later-weaned calves, resulting in different body weight at 100 d (104 vs. 121 ± 1.3 kg). Although earlier-weaned calves could compensate for the loss of CMR dry matter and crude protein intake from d 56 to 100 by increasing forage intake, they were unable to compensate for the loss of energy from the CMR by increasing solid feed consumption. Plasma β-hydroxybutyrate concentrations were 52% greater in earlier-weaned calves than in later-weaned calves at d 84, indicating greater metabolic activity of the rumen wall. The duration of CMR feeding had no influence on humoral or cell-mediated immune functions of the calves, as evidenced by a lack of effect on antivaccine antibody responses as well as on immune gene expression. Earlier- versus later-weaned heifer calves had 5% lower mammary gland mass, indicating that greater energy supply increased mammary mass. The results of this experiment demonstrate the ability to artificially rear dairy calves on a conserved alfalfa as the only solid feed. Furthermore, earlier weaning off CMR promotes solid feed intake and an associated increase in blood β-hydroxybutyrate, an indicator of rumen development, but increasing the duration of CMR feeding improves growth and mammary gland mass by d 100. The implications of these findings on lifetime growth, health, and milk production in dairy heifers warrant further investigation.     

Postscript: UN & EM OR EN: Littered Texts En-During the Margin

Homage to the page, the colour of the text: An ancient metaphor: thought is a thread, and the raconteur is a spinner of yarns—but the true storyteller, the poet, is a weaver. The scribes made this old and audible abstraction into a new and visible fact. After long practice, their work took on such an even, flexible texture that they called the written page a textus, which means cloth.1 ?1. Robert Bringhurst, The Elements of Typographic Style, 3rd edn., Point Roberts, WA: Hartley & Marks, 2004, 25.      

Intrauterine high dose rate afterloading brachytherapy: experience of fractionated therapy using a cervical sleeve technique

Using a standard three-channel Manchester-type tube and ovoid high dose rate applicator system, 46 consecutive patients have been treated for carcinoma of the cervix or endometrium. To facilitate fractionated treatments using high dose rate afterloading, a technique has been developed using an indwelling cervical sleeve inserted under an initial general anaesthetic. All patients received at least two insertions; in five patients we have delivered a total of six consecutive fractions on an outpatient basis without anaesthesia once the sleeve was in situ. Acute morbidity related to the procedure was some degree of uterine pain, which was relieved with nitrous oxide inhalation, and mild, but self-limiting, vaginal discharge. Complete late morbidity data are not yet available, but, in 30% of 25 evaluable patients, minor problems have been observed, particularly vaginal oedema and stenosis. Only one major late event has required surgery. Fractionated afterloading intrauterine brachytherapy can be delivered on an outpatient basis without anaesthesia using this cervical sleeve technique.     

Accelerated radiotherapy, carbogen and nicotinamide (ARCON) in locally advanced head and neck cancer: a feasibility study

BACKGROUND AND PURPOSE: ARCON (Accelerated Radiotherapy, CarbOgen, Nicotinamide) achieves a large therapeutic gain in rodents. A phase I/II study was therefore undertaken to determine its feasibility in patients with locally advanced head and neck cancer. MATERIALS AND METHODS: The accelerated regime CHART was used in 35 patients given carbogen and/or nicotinamide with 11 small volume fractions. Eight patients received carbogen, 12 received nicotinamide and 15 were treated with ARCON. Treatment compliance, side-effects and acute mucositis were monitored in all cases. RESULTS: All patients underwent CHART as intended. In the 23 patients receiving carbogen, two failed to complete treatment. Compliance with nicotinamide was much lower. Out of 25 patients, only 52% received 10-11 doses of the 80 mg/kg/day of the drug. The most common side-effect was nausea and vomiting, which responded to standard anti-emetics in almost half of the patients. Historical comparisons with the CHART head and neck trials indicate that there was no increase in the severity of acute mucositis in any of these patients. Although the observation period is not sufficiently long to be definitive (median 20 months) there is no evidence of an increase in late normal tissue reactions. CONCLUSIONS: ARCON using CHART as the radiotherapy protocol is feasible in patients with advanced head and neck cancer. However, we are concerned about the low compliance rate in our patients, which is far lower than that reported elsewhere. The implications are discussed together with identifying strategies for increasing compliance.     

Money Management After Acquired Brain Dysfunction: The Validity of Neuropsychological Assessment.

Objective: To study the money management ability of people with acquired brain dysfunction (ABD) and its relationship to neuropsychological test performance. Subjects or Other Participants: 35 people with ABD and 15 matched controls without ABD. Main Outcome Measures: Case managers completed an experimenter-designed Money Management Survey (MMS), a staff-rating measure of the client's money management abilities. Results: In addition to the problems identified by controls, the group with ABD had other difficulties such as not leaving money aside for essentials and using automatic teller machines. Neuropsychological assessment demonstrated a modest ability to predict the overall MMS, however, the prediction of specific behaviors (problematic impulsive spending and paying the bills or rent late) was more successful. Conclusion: These results provide support for the use of the MMS and indicate that people with ABD have greater problems with specific aspects of money management than do controls. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhibition of anti-CD3 antibody-induced mouse T cell activation by pentoxifylline in combination with rapamycin or A77 1726 (leflunomide)

Pentoxifylline (PTX), rapamycin (RAP), and leflunomide are potent immunomodulatory drugs with differing modes of action. In order to develop new drug combinations for immunotherapy, we tested the effects of PTX in combination with RAP or A77 1726 (the active metabolite of leflunomide) on in vitro T cell activation in a mouse model system. T lymphocytes in spleen cell preparations were stimulated with anti-CD3 monoclonal antibody alone, or in the presence of PTX (25-200 microg/ml), RAP (0.5-5.0 ng/ml), A77 1726 (2.5-10.0 microM), PTX/RAP (25-200 microg/ml and 0.5-5.0 ng/ml, respectively), or PTX/A77 1726 (25-200 microg/ml and 2.5-10.0 microM, respectively). Anti-CD3-induced T cell proliferation was inhibited in a dose-dependent fashion by the individual drugs. An additive inhibitory effect was observed in cultures treated with PTX/RAP or PTX/A77 1726. The effects of PTX, RAP, A77 1726, PTX/RAP, or PTX/A77 1726 (at concentrations approximating the IC50 of individual drugs for inhibition of lymphoproliferation) on anti-CD3-activated killer (AK) cell induction, CD25 expression, and interleukin (IL)-2 synthesis in anti-CD3-activated spleen cell cultures were also determined. Alone, each drug was able to suppress AK cell induction to varying degrees. PTX plus RAP exhibited strong synergism, while the combination of PTX and A77 1726 had an additive inhibitory effect on AK cell induction. CD25 expression was only weakly inhibited by A77 1726, but the percentage of CD25-expressing cells was greatly reduced in cultures treated with PTX or RAP. The combination of PTX and RAP had an additive inhibitory effect on CD25 expression while PTX and A77 1726 together had an effect equivalent to PTX alone. IL-2 synthesis was inhibited by PTX but was unaffected by RAP or A77 1726. Treatment with PTX plus RAP led to a further reduction in IL-2 production but co-treatment with PTX and A77 1726 approximated the inhibitory effect of PTX alone. We conclude that the combination of PTX and RAP is noteworthy for its potent immunomodulatory activity and may be of use in clinical situations where it is desirable to prevent T cell activation.