Expression of pS2, c-erbB-2, and cathepsin D during the menstrual cycle in human breast cancers

Background: Many studies have addressed the effect of the timing of surgery for breast cancer relative to menstrual cycle phase, with conflicting results. Explanations for the possibility that survival could be altered by the appropriate timing of breast cancer surgery in humans remain speculative. Methods: We examined the expression of three estrogen related proteins (c-erbB-2, cathepsin D, pS2) in the breast tumors from 69 premenopausal women sampled in different phases of the menstrual cycle. Data on S-phase fraction and hormone receptor expression were also analyzed. Immunohistochemical assays were used to measure the proteins of interest. S-phase fraction was determined by flow cytometry. Analyses were performed based on fraction of cells staining positive for the protein, density of stain, and a histoscore that combined both fraction of positive cells and density. Results: We found no differences in c-erbB-2, cathepsin D, hormone receptor, or S-phase levels in tumors sampled in the follicular versus luteal phase, or perimenstrual versus periovulatory phase. The exception was pS2, which was expressed at greater levels during the luteal than during the follicular phase of the cycle (p<0.01); but there was no difference in pS2 expression when the patients were classified as periovulatory versus perimenstrual. Conclusions: Our findings do not support a variation in c-erbB-2, cathepsin D, S-phase fraction, or receptor expression as an explanation for the differences in breast cancer prognosis when surgery is timed by menstrual cycle phase. The finding that pS2 (an indicator of hormone sensitivity, and possibly better prognosis) is expressed at higher levels in tumor samples during the luteal phase suggests that the biologic profile of breast tumors may vary with the menstrual cycle and that these variations deserve further study.     

Melbourne trial of adjuvant immunotherapy in operable large bowel cancer

A controlled randomized clinical trial was undertaken to assess the ability of combined non-specific and specific immunotherapy to alter the disease-free interval and overall survival of patients with Stage B or C large bowel cancer. The immunotherapy consisted of a 2 year programme of vaccinations with BCG and neuraminidase-treated autologous tumour cells. Three hundred and one patients entered the trial. At 5 years of follow-up there is no evidence that this form of immunotherapy can alter either the disease-free interval or survival in this group of patients.     

Nurses' Logs as an Evaluation Tool for School-Based Violence Prevention Programs

ABSTRACT: Programs for preventing violence among youth should be evaluated to determine if they are effective. Nurses' logs appear to be a useful tool for evaluating school-based violence prevention programs. The logs provide a record of students' visits to the school nurse that can be used to determine if a violence prevention program is associated with a reduction in fighting—and other injury-related nurse visits. This method has many strengths: it is simple and inexpensive, it does not interrupt the school routine, it permits school-level rather than student-level data collection, it provides a ready "baseline," and it allows continuous data collection. However, potential limitations do exist. For example, the method may provide insufficient information and may be affected by factors unrelated to the intervention. School officials can increase the usefulness of the logs by encouraging standardization and providing training in their use.     

Increased incidence of gap junctional coupling between spinal motoneurones following transient blockade of NMDA receptors in neonatal rats

Neonatal rat motoneurones are electrically coupled via gap junctions and the incidence of this coupling declines during postnatal development. The mechanisms involved in this developmental regulation of gap junctional communication are largely unknown. Here we have studied the role of NMDA receptor-mediated glutamatergic synaptic activity in the regulation of motoneurone coupling. Gap junctional coupling was demonstrated by the presence of graded, short latency depolarising potentials following ventral root stimulation, and by the transfer of the low molecular weight tracer Neurobiotin to neighbouring motoneurones. Sites of close apposition between the somata and/or dendrites of the dye-coupled motoneurones were identified as potential sites of gap junctional coupling. Early postnatal blockade of the NMDA subtype of glutamate receptors using the non-competitive antagonist dizocilpine maleate (MK801) arrested the developmental decrease in electrotonic and dye coupling during the first postnatal week. These results suggest that the postnatal increase in glutamatergic synaptic activity associated with the onset of locomotion promote the loss of gap junctional connections between developing motoneurones.     

International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson's disease: the NMSQuest study.

Nonmotor symptoms (NMS) of Parkinson's disease (PD) are not well recognized in clinical practice, either in primary or in secondary care, and are frequently missed during routine consultations. There is no single instrument (questionnaire or scale) that enables a comprehensive assessment of the range of NMS in PD both for the identification of problems and for the measurement of outcome. Against this background, a multidisciplinary group of experts, including patient group representatives, has developed an NMS screening questionnaire comprising 30 items. This instrument does not provide an overall score of disability and is not a graded or rating instrument. Instead, it is a screening tool designed to draw attention to the presence of NMS and initiate further investigation. In this article, we present the results from an international pilot study assessing feasibility, validity, and acceptability of a nonmotor questionnaire (NMSQuest). Data from 123 PD patients and 96 controls were analyzed. NMS were highly significantly more prevalent in PD compared to controls (PD NMS, median = 9.0, mean = 9.5 vs. control NMS, median = 5.5, mean = 4.0; Mann-Whitney, Kruskal-Wallis, and t test, P < 0.0001), with PD patients reporting at least 10 different NMS on average per patient. In PD, NMS were highly significantly more prevalent across all disease stages and the number of symptoms correlated significantly with advancing disease and duration of disease. Furthermore, frequently, problems such as diplopia, dribbling, apathy, blues, taste and smell problems were never previously disclosed to the health professionals.     

Obesity in Pima Indians. Distribution characteristics and possible thresholds for genetic studies.

We examined distribution characteristics of the body mass index (BMI; weight/height; kg/m2) in a sample of 1128 male and 1372 female Pima Indians aged 15-65 years. We found that women had a higher mean and variance of BMI than men. From commingling analyses, we determined that the distribution of BMI could be accounted for either by a single skewed distribution or by a mixture of multiple normal components. These component distributions may be used to define provisional thresholds in selecting families for genetic studies. To ensure genetic segregation of obesity predisposing genes in Pima families will require that some members have BMIs > or = 40 kg/m2.     

Cationic lipids enhance cellular uptake and activity of phosphorothioate antisense oligonucleotides.

We have investigated the use of a cationic lipid preparation to enhance antisense oligonucleotide activity in human umbilical vein endothelial cells. A liposomal preparation containing the cationic lipid N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA) was found to increase by at least 1000-fold the potency of an antisense oligonucleotide (ISIS 1570) that hybridizes to the AUG translation initiation codon of human intercellular adhesion molecule-1. In the presence of 8 microM DOTMA, 6-15-fold more 35S-ISIS 1570 associated with cells, at oligonucleotide concentrations from 0.01 to 5 microM, than did in the absence of DOTMA. Both 35S-ISIS 1570 association with cells and antisense activity were increased as a function of DOTMA concentration and with increasing time of incubation with the cationic lipid. Fluorescein-labeled ISIS 1570 was used to assess the intracellular distribution of the oligonucleotide in the presence and absence of DOTMA. In the absence of DOTMA, the oligonucleotide localized to discrete structures in the cytoplasm of the cell, resulting in a punctate fluorescence pattern. In the presence of DOTMA, cellular fluorescence markedly increased and the oligonucleotide localized within the nucleus, as well as to discrete structures in the cytoplasm. Accumulation of the oligonucleotide in the nucleus in the presence of DOTMA was time and temperature dependent. Nuclear accumulation was inhibited by preincubation of the cells with monensin but not chloroquine, NH4Cl, nocodazole, colcemid, or brefeldin A. These data demonstrate that cationic lipids increase antisense activity by increasing the amount of oligonucleotide associated with cells and altering intracellular distribution of the oligonucleotide.