Effects of high and low dietary fat and indomethacin on tumour growth, hormone receptor status and growth factor expression in DMBA-induced rat breast cancer.

The effects of high and low dietary fat (20% vs. 0.5% corn oil), and of the prostaglandin synthetase inhibitor indomethacin (0.005% w/w), on tumour incidence, tumour growth, hormone-receptor status and growth-factor expression were examined in dimethylbenzanthracene (DMBA)-induced rat breast cancer. The high dietary-fat group showed a significantly higher tumour incidence, larger tumour size and larger number of bromodeoxyuridine(BrdU)-positive cells of tumours as compared with those in the low dietary-fat group. Indomethacin reduced tumour incidence significantly, but conversely increased the tumour size and the number of BrdU-positive cells in both the high and the low dietary-fat groups. No significant difference was noted in the hormone-receptor status of the tumours. Growth factors (TGF-alpha and IGF-II) were somewhat highly expressed in the high dietary-fat group as compared with the low dietary-fat group, but indomethacin rather reduced the growth-factor expression. It is concluded that high dietary fat stimulates tumour incidence and tumour proliferation, while indomethacin has dual effects: a stimulating effect on tumour proliferation, but an inhibiting effect on tumour incidence. It is also suggested that hormone-receptor status and growth-factor expression do not play an important role in their stimulating effects on tumour proliferation.     

Heart rate reactivity and heart period variability throughout the first year after heart transplantation

Heart rate reactivity to mental stress is substantially blunted early after heart transplantation, suggesting that the loss of neural modulation limits the cardiovascular response to mental stress. We tested whether reactivity to mental stress recovers during the first year after heart transplantation. Hemodynamic and respiratory responses to mental arithmetic challenge were studied in 20 heart transplant recipients 3, 6, and 12 months after surgery. A normal comparison group was studied at equivalent intervals. Heart rate reactivity to mental arithmetic was significantly reduced in the cardiac transplant group compared to the normal subjects. This effect persisted up to 1 year after transplantation. Heart period variability in the heart transplant recipients was minimal in all three-test sessions. The findings suggest that no functional reinnervation or other compensatory adaptation occurs up to 1 year after heart transplantation.     

An immunogenetic analysis of the T-cell recognition of the major house dust mite allergen Der p 2: identification of high- and low-responder HLA-DQ alleles and localization of T-cell epitopes.

Cellular reactivity to Der p 2, a major allergen of the house dust mite (HDM) Dermatophagoides pteronyssinus, was studied in a group of 41 symptomatic HDM sensitive patients, using fresh peripheral blood mononuclear cells (PBMC) and assays of proliferation. Sixty per cent of the patients responded to Der p2, with reactivities being greater in patients with asthma as one of their clinical manifestations and also in those who had skin-test reactivity to a number of allergens. HLA-DR and -DQ serotyping was undertaken in 39 of the patients and the magnitude of T-cell proliferative responses to Der p 2 were found to be positively associated with DQ7 and negatively associated with DQ2. T-cell determinants within the Der p 2 molecule were identified by assays using a series of overlapping peptides (15- to 19-mers) spanning the entire protein. Fifty-nine per cent of the 41 HDM-sensitive patients responded to one or more of the peptides. All of the peptides were antigenic for at least one of the individuals, indicating the heterogeneity of the human repertoire reactive with Der p 2. There was a substantial variability in the number and location of epitopes recognized by T cells from the different allergic patients, the mean number per patient being 2.3 +/- 1.3 (SD). The most frequently recognized peptide was that spanning residues 111-129, being stimulatory in 66.7%, the other peptides were each recognized by between 8 to 25% of individuals. There was no correlation between the epitope recognized and the presence of particular HLA-DQ antigens.     

A simple and versatile harvesting device for processing radioactive label incorporated into and-or released from cells in microculture

The difficulty with microculture systems is not in growing small numbers of cells in the wells of microtiter plates, but in harvesting, washing and processing these cells or their supernatants for radioactive counting. The logistical advantage of microculture techniques has prompted development of a simplified and versatile microculture harvesting device which can process cell precipitates as well as cell supernatants, can be made by any machine shop, and has proven extremely useful in a laboratory of immunology.     

A 2-week efficacy and safety study of eszopiclone in elderly patients with primary insomnia

STUDY OBJECTIVES: Evaluate the efficacy of eszopiclone in primary insomnia. DESIGN/SETTING: Randomized, double-blind, placebo-controlled multicenter in outpatient setting with weekly visits. PARTICIPANTS: Two-hundred thirty one men and women aged 65 to 85 years (mean age 72.3 years) with primary insomnia, as defined by the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition. INTERVENTIONS: Eszopiclone 1 mg (n = 72), eszopiclone 2 mg (n = 79), or placebo (n = 80) nightly for 2 weeks. MEASUREMENTS/RESULTS: Efficacy was assessed using an interactive voice response system. Following the predefined hierarchical testing strategy, the eszopiclone 2-mg group had a significantly shorter sleep latency compared with placebo over the double-blind period (P = .0034). The eszopiclone 2-mg group had significantly longer total sleep time (P = .0003) and eszopiclone 1-mg group had significantly shorter sleep latency (P < or = .012) compared with placebo. The eszopiclone 1-mg group was not significantly different from placebo on total sleep time or any other secondary efficacy endpoint. Secondary analyses indicated that the eszopiclone 2-mg group had significantly less wake after sleep onset; significantly fewer and shorter in duration daytime naps; and significantly higher ratings of sleep quality and depth, daytime alertness, and sense of physical well-being compared with placebo (P < .05). Eszopiclone was well tolerated. The most frequent treatment-related adverse event was unpleasant taste. CONCLUSION: Nightly treatment with eszopiclone 1 mg effectively induced sleep, while the 2-mg dose was effective in inducing and maintaining sleep. Eszopiclone was well tolerated in elderly patients with primary insomnia, and the sleep efficacy was accompanied by significantly less napping and significantly higher ratings of daytime alertness, sense of physical well-being, and several quality-of-life parameters at the higher dose.     

Investigation of 89 candidate gene variants for effects on all-cause mortality following acute coronary syndrome

Background  

Many candidate genes have been reported to be risk factors for acute coronary syndrome (ACS), but their impact on clinical prognosis following ACS is unknown.     

Conditioned Diastolic Blood Pressure as a Function of Induced Masseter Muscle Tension

The purpose of this study was twofold: 1) to attempt to replicate a previous study in which subjects were trained to produce bi-directional changes in diastolic BP as great as 10% to 15% of baseline, and 2) to determine whether the same subjects could acquire such a BP response under conditions of induced muscle tension. A 2x3 design was used in which 24 subjects were randomly assigned to one of two training procedures (feedback vs no feedback), and one of three muscular tension conditions. Acquisition took place over 14 sessions; 7 were used to train UP and 7 were used to condition DOWN responses. Results showed that during UP training, subjects learned to raise their BP in the absence of induced tension, but not when tension was present. However, the same subjects learned to lower their BP with and without induced tension, although their performance under the tension condition was only marginally reliable.     

Pathological aspects of immunization of mice against influenza virus infection.

Groups of mice were immunized against influenza Ao/NWS virus by a single intranasal administration of inactivated homologous virus, by 2 intranasal doses of vaccine separated by an interval of 2 weeks, or by 2 intraperitoneal doses of the same vaccine. When subjected 2 weeks later to a standard challenge of 6 x 10(5) egg infecting units Ao/NWS virus instilled intranasally, mortality fell significantly from 64% in unimmunized mice to 39% in mice given a single intranasal dose of vaccine and to 29% in animals which received double intranasal vaccine. The best protection was conferred by double intraperitoneal immunization, after which mortality was 10%. Immunity waned with time, since the mortality of mice doubly immunized by the respiratory route and challenged 30 weeks later was 49%. Intrapulmonary lymphoid tissue developed in large amounts in a proportion of mice immunized by all methods and challenged after an interval of 2 weeks. Attention is drawn to this reaction as a possible unfavourable consequence of vaccination. There were no lesions in the lungs or central nervous system after immunization without subsequent challenge. The importance of histopathology in vaccine trials in experimental animals is emphasized by the consistently higher detection rate of lesions in lungs by histological examination than by visual inspection alone.