Functional consequences of the first reported mutations of the proto-oncogene PTTG1IP/PBF.

Pituitary tumor-transforming gene 1-binding factor (PTTG1IP; PBF) is a multifunctional glycoprotein, which is overexpressed in a wide range of tumours, and significantly associated with poorer oncological outcomes, such as early tumour recurrence, distant metastasis, extramural vascular invasion and decreased disease-specific survival. PBF transforms NIH 3T3 fibroblasts and induces tumours in nude mice, while mice harbouring transgenic thyroidal PBF expression show hyperplasia and macrofollicular lesions. Our assumption that PBF becomes an oncogene purely through increased expression has been challenged by the recent report of mutations in PBF within the Catalogue of Somatic Mutations in Cancer (COSMIC) database. We therefore sought to determine whether the first 10 PBF missense substitutions in human cancer might be oncogenic. Anisomycin half-life studies revealed that most mutations were associated with reduced protein stability compared to wild-type (WT) PBF. Proliferation assays narrowed our interest to two mutational events which significantly altered cell turnover: C51R and R140W. C51R was mainly confined to the endoplasmic reticulum while R140W was apparent in the Golgi apparatus. Both C51R and R140W lost the capacity to induce cellular migration and significantly reduced cell invasion. Colony formation and soft agar assays demonstrated that, in contrast to WT PBF, both mutants were unable to elicit significant colony formation or anchorage-independent growth. However, C51R and R140W retained the ability to repress radioiodide uptake, a functional hallmark of PBF. Our data reveal new insight into PBF function and confirm that, rather than being oncogenic, mutations in PBF are likely to be passenger effects, with overexpression of PBF the more important aetiological event in human cancer.

Changes in intendedness during pregnancy in a high-risk multiparous population.

OBJECTIVES: Our objectives were to determine whether pregnancy intendedness changes as the pregnancy progresses and, if so, in what direction. METHODS: Intendedness questions similar to those used in the 1988 National Survey of Family Growth were administered in the second trimester of pregnancy (16-18 weeks) and again in the third trimester (30-32 weeks) to a population of 1223 low-income women who were medically at high risk. Information was also collected on characteristics identified in previous studies as being associated with intendedness. Changes in reported intendedness status were categorized as positive if the woman switched from unwanted to mistimed or intended or from mistimed to intended. Changes were categorized as negative if the woman switched from intended to mistimed or unwanted or from mistimed to unwanted. RESULTS: Among the 436 women who reported an intended pregnancy at midpregnancy, 79.1% still reported the pregnancy as intended in late pregnancy, while 15.9% moved to mistimed and 6.4% to unwanted. Of the 601 women who reported a mistimed pregnancy in midpregnancy, 80.9% still reported it as mistimed in late pregnancy, with 13.9% switching to intended and 5.2% switching to unwanted. Of the 186 women who reported an unwanted pregnancy at midpregnancy, 62.9% remained unwanted, 30.7% switched to mistimed, and 6.4% switched to intended. CONCLUSIONS: This study indicates that intendedness is not fixed during pregnancy. Between the first and the second administration of the intendedness questions, 275 (22.5%) of the women changed their responses and the larger percentage (12.5%) changed them in a positive direction. These findings have both policy and clinical implications.

Delivery of primary care services among family planning centers: a response to managed care?

Previous case studies indicate that some family planning centers are transforming themselves into providers of primary care services, in part as a strategy to attract managed care contracts. Data for 98 family planning centers from the 1994 National Survey of Women's Health Centers and supplementary sources are used to explore the factors associated with managed care contracting. Although some organizational-level factors are predictive, no cross-sectional association was found between providing primary care and managed care contracting, which suggests family planning centers are not using primary care as a major contracting strategy.

Finding meaning in illness. Can nurses help?

They are common comments from people facing a life-threatening or chronic illness: "Why did this happen to me? I don't deserve this." "Am I being punished for something? Why do I have to go through this?"

Helping others when you are hurting: strategies for delivering quality care while dealing with personal bereavement.

Nurse managers are in a strategic position to assist clients, their family members, and other staff in dealing with normal grief and to provide additional assistance if the grief becomes complicated. A variety of strategies can be used by the nurse to assist individuals through the grief process. In some cases, the nurse must deal with personal grief while simultaneously helping others. This article addresses useful strategies for nurses to enhance the delivery of quality care while dealing with personal loss and grief.

Time-bound madness.

The concept of the passage of time is familiar to most people regardless of ethnic heritage. However, some persons are more time-bound than others. This article discusses the qualities of time-bound individuals and outlines strategies for responding to time-bound madness.

When your patient uses denial.

There are may factors to consider when denial is encountered in a patient situation. Denial is a simple concept but is complicated by ego-maintaining mechanisms that denial may produce. It is important to evaluate each individual situation in order to identify suitable approaches for the situation. Denial may not be something that the nurse should take away since it can serve an important balancing function between depression and wellness.

Growing older is not what it used to be.

Growing old is not what it used to be. Many self-care actions can enhance one's chance of growing old without illness or disease. This necessitates preparing for old age while one is young. Preparation for second adulthood can vastly improve physical and emotional health in old age. It is important that nurses and other health care professionals teach health promotion strategies to persons at all ages in order to assist individuals to live life to its fullest throughout their lifetime.

Death, dying and grief in a transcultural context: application of the Giger and Davidhizar assessment model.

One of the most challenging aspects of death education and grief counseling is providing care and education that is relevant to the cultural, racial, and ethnic needs of the client. Often appropriate responses are difficult due to the lack of a relevant model; otherwise practitioners tend to operate from facts collected in isolation. This article reports on an assessment model originally developed in nursing by Giger and Davidhizar and discusses its potential use in providing culturally relevant death education and grief counseling.

When change is a must.

Change is a significant concept in health care. It is critical that health care professionals understand change dynamics and implement strategies to adapt to the changes in the modern workplace.

When your employee forgets who the boss is.

Managers confront many types of behavior in the workplace. One interpersonal problem that presents an unusual challenge to the manager is the employee who appears to "forget who the boss is." This article addresses this unusual employee-manager problem by first describing the characteristics and dynamics of the behavior and then providing guidelines for responding to this problematic behavior.

The interview that wins the job.

Obtaining a nursing position is often the first challenge for the graduate nurse. Understanding the interview process and making a plan that will ensure the graduate is placed in the best possible light is important for success in the interview process. This paper discusses getting ready for the interview, setting up the interview, dressing for the interview, the actual interview and following up the interview. Adherence to these guidelines can facilitate the graduate's success in obtaining the desired position.

Health promotion among ethnic minorities: the importance of cultural phenomena.

Ethnic minority groups have varying health promotion needs, which differ according to six cultural phenomena outlined in the nursing literature: communication, space, social organization, time, environmental control, and biological variations. This article reports on some of the research available in each of these areas in relation to ethnic minorities. If health promotion is to be improved for people in all sectors of the population, it is important for rehabilitation nurses to learn how to assess the needs of ethnic minorities and to respond to those needs with appropriate interventions.

Family planning: an essential component of prenatal care.

This nation's traditional approach to improving maternal and infant health has been prenatal care. But evidence is mounting that additional progress in reducing maternal and infant morbidity and mortality will depend, at least in part, on the care that a woman receives before she conceives. The studies reviewed in this paper indicate that increasing the interval between deliveries and preventing or delaying pregnancies among women at high risk could lower the rate of low birthweight (LBW). Since reducing the rate of unintended pregnancies would also reduce the number of pregnancies in women at high risk of LBW because of race, age, late or no prenatal care, and unhealthy behaviors, the prevention of unintended pregnancies would also reduce LBW. Unfortunately, prenatal care, as experienced by many women, devotes little attention to these family planning issues. Many women do not realize the importance of family planning to their own health and that of their children. Prenatal care providers should include instruction about the importance of pregnancy planning and encourage women to continue receiving health care between pregnancies. If the health of women and infants is to be improved, society must be willing to provide health services to women of reproductive age even when they are not pregnant.