The adenoma-carcinoma sequence in the colorectum--early appearance of a hierarchy of small intestinal mucin antigen (SIMA) epitopes and correlation with malignant potential.

The colorectal adenoma-carcinoma sequence was examined in relation to the ectopic expression of the oncofoetal Small Intestinal Mucin Antigen (SIMA), to the development of morphologic changes in the adenoma and perineoplastic mucosa and to indices of malignant potential. Four anti-SIMA MAbs, which define a novel hierarchy of SIMA epitopes in the normal small intestine and adjacent to colorectal cancers, were used in a retrospective immunohistochemical study of Familial Adenomatous Polyposis (FAP, n = 183) and non-familial (n = 44) adenomas. Inappropriate expression of SIMA epitopes was first detected in mucosa adjacent to minute microadenomas larger than three glands, and with increase in size, in increasing amounts within adenomas themselves, but not with microadenomas smaller than three glands or regions of flat mucosa free of adenomas. SIMA epitope expressed in mucosa adjacent to adenomas preceded changes in perineoplastic morphology, which progressed with adenoma growth to resemble transitional mucosa (TM) adjacent to cancers. Thus, the onset of both SIMA expression and morphological changes in TM were consistent with reactive rather than pre-existing field change phenomena. The previously reported hierarchy of four SIMA epitopes (5C5, 3D4, 4D3, 6C5) was also consistently observed in the adenoma-carcinoma sequence, and applied to (i) the order of epitope detection, (ii) the number of positive adenomas and (iii) extent of staining; (iv) the height in the crypt and (v) distance from the adenoma to which epitopes were expressed in perineoplastic mucosa. These observations are consistent with a progression of changes in mucin composition with adenoma development. The percentage of positive adenomas and reactivity scores for each anti-SIMA MAb correlated with increasing adenoma size, degree of dysplasia and growth pattern. SIMA expression appears to predate the earliest reported oncogene and tumour suppressor gene changes, was persistent and increased throughout adenoma development. SIMA epitopes are thus markers of very early neoplastic change, whose expression correlates with malignant potential and may contribute to the accumulation of changes necessary for tumourigenesis

Aberrant expression of intestinal mucin antigens associated with colorectal carcinoma defined by a panel of monoclonal antibodies.

Small intestine mucin antigen (SIMA) is an oncofoetal antigen for the colon and is distinct from the normal large intestinal mucin antigen (LIMA). In the present study, a panel of anti-SIMA and anti-LIMA monoclonal antibodies (MAb) was used to charaterise altered mucin expression in colorectal adenocarcinomas, by immunohistochemistry and quantitative immunoassays of tissue extracts. These results are compared with CEA expression and correlated with various clinicopathological indices. All mucin MAb reacted with a high proportion of the 100 colon cancers of every stage, histological type (including non-mucinous cancers), differentiation, site, or size. Inappropriate SIMA production was detected by either anti-SIMA MAb 4D3 or 4A1, even in 85% of early stage cancers. MAb 4D3 reacted with a higher proportion of cancers of smaller size and better differentiation. At the subcellular level, both anti-SIMA MAb showed reactivity typical of normal mucin, i.e., goblet cell and extracellular mucin. The normal colonic antigen, LIMA, was also detectable in the majority of cases, but quantitatively overproduced in some cases and reduced in others. However, in contrast to SIMA, LIMA was detected in predominantly undifferentiated cancer cells but not in goblet cells. Heterogeneity of MAb reactivity between cases and complementarity within each cancer was frequently observed. Mucin reactive with at least one of the MAb was detected in all of the CEA-negative cancers. A high rate of inappropriate SIMA expression was also detected in the perineoplastic transitional mucosa (88%, c.f. CEA, 35%) and adjacent, morphologically normal mucosa (80% c.f. CEA, 24%), indicating biochemical changes similar to the cancer. This panel of anti-mucin MAb demonstrated altered mucin glycoprotein metabolism associated with the development and progression of most colorectal cancers, which emphasises their utility as indicators of neoplastic change in the colon, and their superiority to CEA

Transcript Profiling of Elf5+/− Mammary Glands during Pregnancy Identifies Novel Targets of Elf5

Background: Elf5, an epithelial specific Ets transcription factor, plays a crucial role in the pregnancy-associated development of the mouse mammary gland. Elf5 2/2 embryos do not survive, however the Elf5 +/2 mammary gland displays a severe pregnancy-associated developmental defect. While it is known that Elf5 is crucial for correct mammary development and lactation, the molecular mechanisms employed by Elf5 to exert its effects on the mammary gland are largely unknown. Principal Findings: Transcript profiling was used to investigate the transcriptional changes that occur as a result of Elf5 haploinsufficiency in the Elf5 +/2 mouse model. We show that the development of the mouse Elf5 +/2 mammary gland is delayed at a transcriptional and morphological level, due to the delayed increase in Elf5 protein in these glands. We also identify a number of potential Elf5 target genes, including Mucin 4, whose expression, is directly regulated by the binding of Elf5 to an Ets binding site within its promoter. Conclusion: We identify novel transcriptional targets of Elf5 and show that Muc4 is a direct target of Elf5, further elucidatin

Maintenance of activity and eating change after a clinical trial of tailored newsletters with older rural women.

BACKGROUND: In the Wellness for Women Project, a randomized-by-site 1-year controlled clinical trial, the efficacy of generic newsletters and newsletters tailored on Health Promotion Model behavior-specific cognitions, eating behavior, and activity behavior were compared among 225 women aged 50 to 69 years. OBJECTIVES: The purpose of this study was to compare the maintenance of change in healthy eating and physical activity over the 12 months following the tailored versus generic mailed newsletter intervention. METHODS: Outcomes at 18 and 24 months included behavioral markers and biomarkers of physical activity and eating. Data were analyzed using the multivariate approach to repeated measures analysis of variance and generalized estimating equations (alpha \u3c.05). RESULTS: At 18 months, the tailored group maintained levels of all eating and activity behaviors, whereas the generic group maintained levels of fruit and vegetable servings, a moderate or greater activity, stretching exercise, lower body strength and flexibility but increased saturated fat intake and declined in weekly strength exercise and cardiorespiratory fitness. At 24 months, both groups maintained or returned to 12-month levels of all eating behaviors,moderate or greater activity, stretching exercise, and flexibility but declined in cardiorespiratory fitness; the tailored group maintained levels of strength exercise and lower body strength, whereas the generic group decreased in both. A greater proportion of women who received tailored newsletters continued to achieve most Healthy People 2010 criteria for eating and activity. DISCUSSION: Mailed tailored print newsletters were more efficacious than generic newsletters in facilitating maintenance of change in eating and activity for 6 months postintervention. Both tailored and generic newsletters facilitated the maintenance of change in eating behaviors and in moderate or greater physical activity and stretching exercise, whereas tailored newsletters were more efficacious in maintaining change in strength exercise for 12 months postintervention

Clinical trial of tailored activity and eating newsletters with older rural women.

BACKGROUND: Unhealthy diet and lack of physical activity increase rural midlife and older women\u27s risk of chronic diseases and premature death, and they are behind urban residents in meeting Healthy People 2010 objectives. OBJECTIVES: The objective of this study was to compare a tailored intervention based on the Health Promotion Model with a generic intervention to increase physical activity and healthy eating among rural women. METHODS: In a randomized-by-site, community-based, controlled, clinical trial, Wellness for Women, 225 women aged 50 to 69 years were recruited in two similar rural areas. Over 12 months, women received by mail either 18 generic newsletters or 18 newsletters computer tailored on Health Promotion Model behavior-specific cognitions (benefits, barriers, self-efficacy, and interpersonal support), activity, and eating. Outcomes at 6 and 12 months included behavioral markers and biomarkers of physical activity and eating. Data were analyzed by repeated-measures analysis of variance and chi-square tests (alpha \u3c .05). RESULTS: Both groups significantly increased stretching and strengthening exercise and fruit and vegetable servings and decreased percentage of calories from fat, whereas only the tailored group increased moderate or greater intensity activity and decreased percentage of calories from saturated fat from baseline to 6 months. Both groups increased stretching and strengthening exercise, whereas only the tailored group increased moderate or greater intensity activity and fruit and vegetable servings and decreased percentage of calories from fat from baseline to 12 months. Both groups had several changes in biomarkers over the study. A higher proportion of women receiving tailored newsletters met Healthy People 2010 criteria for moderate or greater intensity activity, fruit and vegetable servings, and percentage of calories from fat at 12 months. DISCUSSION: Mailed computer-tailored and generic print newsletters facilitated the adoption of change in both activity and eating over 6 months. Tailored newsletters were more efficacious in facilitating change over 12 months

Study of the reaction pbar p -> phi phi from 1.1 to 2.0 GeV/c

A study has been performed of the reaction pbar p -> 4K using in-flight antiprotons from 1.1 to 2.0 GeV/c incident momentum interacting with a hydrogen jet target. The reaction is dominated by the production of a pair of phi mesons. The pbar p -> phi phi cross section rises sharply above threshold and then falls continuously as a function of increasing antiproton momentum. The overall magnitude of the cross section exceeds expectations from a simple application of the OZI rule by two orders of magnitude. In a fine scan around the xi/f_J(2230) resonance, no structure is observed. A limit is set for the double branching ratio B(xi -> pbar p) * B(xi -> phi phi) < 6e-5 for a spin 2 resonance of M = 2.235 GeV and Width = 15 MeV.Comment: 13 pages, 13 figures, 2 tables, Latex. To be published in Phys. Rev.

Test of candidate light distributors for the muon (g−-2) laser calibration system

The new muon (g-2) experiment E989 at Fermilab will be equipped with a laser calibration system for all the 1296 channels of the calorimeters. An integrating sphere and an alternative system based on an engineered diffuser have been considered as possible light distributors for the experiment. We present here a detailed comparison of the two based on temporal response, spatial uniformity, transmittance and time stability.Comment: accepted to Nucl.Instrum.Meth.

Physics at a Fermilab Proton Driver

This report documents the physics case for building a 2 MW, 8 GeV superconducting linac proton driver at Fermilab.Comment: 52 pages, 15 figure

Measurement of Muon Capture on the Proton to 1% Precision and Determination of the Pseudoscalar Coupling g_P

The MuCap experiment at the Paul Scherrer Institute has measured the rate L_S of muon capture from the singlet state of the muonic hydrogen atom to a precision of 1%. A muon beam was stopped in a time projection chamber filled with 10-bar, ultra-pure hydrogen gas. Cylindrical wire chambers and a segmented scintillator barrel detected electrons from muon decay. L_S is determined from the difference between the mu- disappearance rate in hydrogen and the free muon decay rate. The result is based on the analysis of 1.2 10^10 mu- decays, from which we extract the capture rate L_S = (714.9 +- 5.4(stat) +- 5.1(syst)) s^-1 and derive the proton's pseudoscalar coupling g_P(q^2_0 = -0.88 m^2_mu) = 8.06 +- 0.55.Comment: Updated figure 1 and small changes in wording to match published versio

Discovering the New Standard Model: Fundamental Symmetries and Neutrinos

This White Paper describes recent progress and future opportunities in the area of fundamental symmetries and neutrinos.Comment: Report of the Fundamental Symmetries and Neutrinos Workshop, August 10-11, 2012, Chicago, I