Congressional Receptivity to the Nixon Rationality on Drug Abuse Prevention

In 1972 the Congress of the United States enacted the Drug Abuse Office and Treatment Act (D.A.O.T.A). The passage of this bill marked the first time in the 20th Century that the federal government had produced major legislation that would deal with drug abuse as a disease instead of a crime. Likewise, the enactment and signing of D.A.O.T.A. meant that Richard Nixon would be the first American President to have an executive office which would be charged with the mission of supervising our national effort against drug abuse. (These changes appeared on the surface to be momentous. However, one major question remained to be answered. Did the D.A.O.T.A. really have any substance? The question of whether or not the D.A.O.T.A could provide a meaningful answer to our nation’s drug abuse problems became the starting point for this study. Considering the powerful office and aggressive program that President Nixon had requested in his special message to Congress on drug abuse, the nature of the drug abuse problem in the U.S., and the bill which Congress finally enacted, there appeared to be quite a number of differences between what the President had asked for and what the House and the Senate enacted. Why the Congress did not respond affirmatively to President Nixon\u27s request and why the Congress chose to assert its own conscience, raised a number of questions. President Nixon\u27s aggressive initiative and the casual acceptance of the conference substitute put together by the House and Senate raised still other question marks. This analysis is structured with the objective of examining each segment of the enactment of the D.A.O.T.A; from the announcement of the Nixon proposal to the conference that was finally held. At each juncture, an attempt is made to portray the intentions of President Nixon, the reaction of the House and Senate, the issues that were at stake and the compromises that were made. The evidence, which is evaluated consists of primarily, U.S. Government documents. Secondary accounts of day to day happenings in the White House and Congress were obtained from the New York Times and the Wall Street Journal. Where doubts existed as to the motives of individual participants, an attempt was made to obtain additional information through correspondence. The information, that unfolded, gave credence to the hypothesis that the D.A.O.T.A. was doomed to failure because the Congress did not provide it with a clear mandate to turn the drug abuse problem around. The case of the D.A.O.T.A. produced the scenario of a low level conflict between the President and Congress over drug abuse. In this instance, the Congress stated that it considered the Department of Health, Education, and Welfare the proper place for the long term coordination of drug abuse prevention and not the Executive Office of the President. The enactment of the D.A.O.T.A. laid down the guidelines for federal drug abuse prevention activities in the 1970\u27s. The case of the D.A.O.T.A. established a precedent upon which to gage future presidential-congressional-actions in the area of drug abuse prevention and suggested how Congress might react to any future attempts by a President to increase the power of his executive office and the Presidency

Derivation of Myoepithelial Progenitor Cells from Bipotent Mammary Stem/Progenitor Cells

There is increasing evidence that breast and other cancers originate from and are maintained by a small fraction of stem/progenitor cells with self-renewal properties. Recent molecular profiling has identified six major subtypes of breast cancer: basal-like, ErbB2-overexpressing, normal breast epithelial-like, luminal A and B, and claudin-low subtypes. To help understand the relationship among mammary stem/progenitor cells and breast cancer subtypes, we have recently derived distinct hTERT-immortalized human mammary stem/progenitor cell lines: a K5+/K19− type, and a K5+/K19+ type. Under specific culture conditions, bipotent K5+/K19− stem/progenitor cells differentiated into stable clonal populations that were K5−/K19− and exhibit self-renewal and unipotent myoepithelial differentiation potential in contrast to the parental K5+/K19− cells which are bipotent. These K5−/K19− cells function as myoepithelial progenitor cells and constitutively express markers of an epithelial to mesenchymal transition (EMT) and show high invasive and migratory abilities. In addition, these cells express a microarray signature of claudin-low breast cancers. The EMT characteristics of an un-transformed unipotent mammary myoepithelial progenitor cells together with claudin-low signature suggests that the claudin-low breast cancer subtype may arise from myoepithelial lineage committed progenitors. Availability of immortal MPCs should allow a more definitive analysis of their potential to give rise to claudin-low breast cancer subtype and facilitate biological and molecular/biochemical studies of this disease

MUC1 alters oncogenic events and transcription in human breast cancer cells

INTRODUCTION: MUC1 is an oncoprotein whose overexpression correlates with aggressiveness of tumors and poor survival of cancer patients. Many of the oncogenic effects of MUC1 are believed to occur through interaction of its cytoplasmic tail with signaling molecules. As expected for a protein with oncogenic functions, MUC1 is linked to regulation of proliferation, apoptosis, invasion, and transcription. METHODS: To clarify the role of MUC1 in cancer, we transfected two breast cancer cell lines (MDA-MB-468 and BT-20) with small interfering (si)RNA directed against MUC1 and analyzed transcriptional responses and oncogenic events (proliferation, apoptosis and invasion). RESULTS: Transcription of several genes was altered after transfection of MUC1 siRNA, including decreased MAP2K1 (MEK1), JUN, PDGFA, CDC25A, VEGF and ITGAV (integrin α(v)), and increased TNF, RAF1, and MMP2. Additional changes were seen at the protein level, such as increased expression of c-Myc, heightened phosphorylation of AKT, and decreased activation of MEK1/2 and ERK1/2. These were correlated with cellular events, as MUC1 siRNA in the MDA-MB-468 line decreased proliferation and invasion, and increased stress-induced apoptosis. Intriguingly, BT-20 cells displayed similar levels of apoptosis regardless of siRNA, and actually increased proliferation after MUC1 siRNA. CONCLUSION: These results further the growing knowledge of the role of MUC1 in transcription, and suggest that the regulation of MUC1 in breast cancer may be more complex than previously appreciated. The differences between these two cell lines emphasize the importance of understanding the context of cell-specific signaling events when analyzing the oncogenic functions of MUC1, and caution against generalizing the results of individual cell lines without adequate confirmation in intact biological systems

Myoepithelial cells: good fences make good neighbors

The mammary gland consists of an extensively branched ductal network contained within a distinctive basement membrane and encompassed by a stromal compartment. During lactation, production of milk depends on the action of the two epithelial cell types that make up the ductal network: luminal cells, which secrete the milk components into the ductal lumen; and myoepithelial cells, which contract to aid in the ejection of milk. There is increasing evidence that the myoepithelial cells also play a key role in the organizational development of the mammary gland, and that the loss and/or change of myoepithelial cell function is a key step in the development of breast cancer. In this review we briefly address the characteristics of breast myoepithelial cells from human breast and mouse mammary gland, how they function in normal mammary gland development, and their recently appreciated role in tumor suppression

Myoepithelial cells: their origin and function in breast morphogenesis and neoplasia

The human breast epithelium is a branching ductal system composed of an inner layer of polarized luminal epithelial cells and an outer layer of myoepithelial cells that terminate in distally located terminal duct lobular units (TDLUs). While the luminal epithelial cell has received the most attention as the functionally active milk-producing cell and as the most likely target cell for carcinogenesis, attention on myoepithelial cells has begun to evolve with the recognition that these cells play an active part in branching morphogenesis and tumor suppression. A major question that has been the subject of investigation pertains to how the luminal epithelial and myoepithelial lineages are related and precisely how they arise from a common putative stem cell population within the breast. Equally important is the question of how heterotypic signaling occurs between luminal epithelial and surrounding myoepithelial cells in normal breast morphogenesis and neoplasia. In this review we discuss data from our laboratories and from others regarding the cellular origin of human myoepithelial cells, their function in maintaining tissue polarity in the normal breast, and their role during neoplasia

Improving adherence to ante-retroviral treatment for people with harmful alcohol use in Kariobangi, Kenya through participatory research and action

<p>Abstract</p> <p>Background</p> <p>Harmful alcohol use has been linked to the spread of HIV in Kenya. It also adversely affects those on antiretroviral (ARV) treatment through poor compliance. This study using participatory research and action (PRA) methods sought to understand factors related to alcohol abuse and non-adherence and to formulate appropriate interventions in a sample of people living with HIV and AIDS (PLWHA) who were also abusing alcohol, at Kariobangi in Nairobi, Kenya.</p> <p>Methods</p> <p>Entry into the community was gained through previous PRA work in that community and PLWHA were recruited through snowballing. Working together with the community members, the researchers explored the participants’ understanding of alcohol use problem, its effects on compliance to ARV treatment and discussed possible action areas through PRA techniques that included focus group and market place discussions; visual aids such as spider diagrams, community mapping and ranking. Follow-up meetings were held to discuss the progress.</p> <p>Results</p> <p>By the final meeting, 67 PLWHA and 19 community members had been recruited. Through discussions, misconceptions regarding alcohol use were identified. It emerged that alcohol abuse was poorly recognised among both the community and health workers. Screening for alcohol use was not routinely done and protocols for managing alcohol related disorders were not available at the local health centres providing ARVs. The study participants identified improving communication, psychoeducation and screening for alcohol use as possible action areas. Poverty was identified as a major problem but the interventions to mitigate this were not easy to implement.</p> <p>Conclusion</p> <p>We propose that PRA could be useful in improving communication between the health workers and the clients attending primary health care (PHC) facilities and can be applied to strengthen involvement of support groups and community health workers in follow up and counselling. Integrating these features into primary health care (PHC) would be important not only to PLWHA but also to other diseases in the PHC setting . Longer term follow up is needed to determine the sustained impact of the interventions. Problems encountered in the PRA work included great expectations at all levels fostered by handouts from other donors and cognitive impairment that interfered with constructive engagement in some of the PLWHA.</p