The CD8β polypeptide is required for the recognition of an altered peptide ligand as an agonist

T cell activation is triggered by the specific recognition of cognate peptides presented by MHC molecules. Altered peptide ligands are analogs of cognate peptides which have a high affinity for MHC molecules. Some of them induce complete T cell responses, i.e. they act as agonists, whereas others behave as partial agonists or even as antagonists. Here, we analyzed both early (intracellular Ca²⁺ mobilization), and late (interleukin-2 production) signal transduction events induced by a cognate peptide or a corresponding altered peptide ligand using T cell hybridomas expressing or not the CD8 α and β chains. With a video imaging system, we showed that the intracellular Ca²⁺ response to an altered peptide ligand induces the appearance of a characteristic sustained intracellular Ca²⁺ concentration gradient which can be detected shortly after T cell interaction with antigen-presenting cells. We also provide evidence that the same altered peptide ligand can be seen either as an agonist or a partial agonist, depending on the presence of CD8β in the CD8 co-receptor dimers expressed at the T cell surface.     

'Now and Again It Really Hits Me': The Impact of an HIV-positive Diagnosis upon Psychosocial Well- being

Quantitative and qualitative data were gathered from a sample of 66 seropositive and 67 seronegative men and women about the impact of an HIV diagnosis upon psychosocial well-being. No significant differences between seropositives and seronegatives were found on any of the psychosocial measures except hopelessness. Nor was there significant variation by disease progression (but this may be due to the restricted size of the sample). The qualitative data are used to illustrate these findings and explore their meaning. It is concluded that, with the exception of a hopeless future orientation, psychosocial disturbance of seropositives tends to be episodic and short-lived and thereby difficult to measure.     

Effects of childhood leukemia and chemotherapy on puberty and reproductive function in girls.

Longer survivial in childhood leukemia prompted this study of pubertal development and reproductive function in 35 girls and women. Twenty-eight patients (80 per cent) had normal pubertal progression during a median of 74 months after diagnosis of leukemia and 49 months of chemotherapy. Seven patients were abnormal: four exhibited hypothalamic-pituitary dysfunction with suppression of circulating serum gonadotropins (less than 6 mlU per milliliter); three others had evidence of primary ovarian dysfunction - reversible in two - with inappropriately elevated circulating serum gonadotropins (follicle-stimulating hormone greater than 20 mlU per milliliter). Normal sexual development correlated best with pubertal status at onset of leukemia; only one of 17 patients with diagnosis before puberty experienced altered pubertal progression, whereas abnormalities appeared in six of 18 with onset during puberty or after menarche. Thus, most girls with aggressively treated child-hood leukemia have an excellent prognosis for normal hypothalamic-pituitary-ovarian function; normal development is further enhanced in patients who are prepubertal at onset of leukemia.     

Cytogenetic studies on acute nonlymphocytic leukemia in relapse

Karyotypic abnormalities were compared in 42 acute nonlymphocytic leukemia patients at diagnosis and in relapse. Clonal changes were observed in 21 cases. The types of changes were the appearance of clonal abnormalities in relapse in four patients without clonal changes at diagnosis, the detection of new abnormalities superimposed on preexisting ones in 11 cases, and the selection of an abnormal clone in six others. Nonclonal structural abnormalities, mainly involving chromosomes 17 and 12p, were detected in relapse in 17 patients, compared to seven at diagnosis. The appearance of totally new clonal changes at relapse and the role of individual sensitivity to chemotherapy are discussed.     

Liaison psychiatry: a service for averting dehumanization of medicine. Recent psychosocial changes in medicine

Recent technical advances of medical science have become responsible for the altered role of the physician and changes in the practice of medicine. As the practice has become hospital-centered, the importance of the individual physician and the prestige of the medical profession have markedly decreased. Dehumanization of medicine has been a natural outcome of these changes, for as the scientific approach to patient care increased the psychosocial support of the physician and significant others decreased. Liaison psychiatry, the therapeutic arm of psychosomatic medicine, utilizes the holistic principle which incorporates the psychosocial nuances of human behavior into the medical model. It is felt that this service must be utilized with increased frequency if further dehumanization of medical practice is to be prevented.     

Impact of management change and an intervention program on health care personnel

BACKGROUND: There has been a major shift in the organization and responsibility for the provision of geriatric care in Sweden. This was believed to be stressful. We therefore decided to launch a controlled intervention program on health care personnel aimed at enhancing their adaptation and ability to cope. The purpose of this study was to assess the impact of management change on psychosocial parameters of health care personnel and the effects, if any, of a structured intervention program. METHODS: Two separate wards were randomly allocated to be either intervention (I) or control (C) ward. The I-ward personnel were subjected to a psychologist's structured 10-session intervention program for 20 weeks. The program consisted of an initial educational part followed by a practical problem-solving discussion part. A structured questionnaire on psychosocial issues was answered by the participants before (0 weeks), immediately after (20 weeks), and 10 weeks after the intervention (30 weeks). RESULTS: There were no significant changes in the psychosocial parameters of the C-ward personnel. In the I-ward, however, there was a significant increase in work demand as well as in positive feelings about work, as compared to the C-ward at the 30-week follow-up. There was also significantly better work comfort in the I-ward. CONCLUSIONS: We did not find any anticipated negative psychosocial effects on health care personnel undergoing an organizational change. However, by offering a structured intervention program to one group of health care personnel, we found some positive psychosocial effects. Future research is needed to pinpoint which factor or factors in the intervention program were the most crucial for the effects to occur.     

Alteration of enzymes in ageing human fibroblasts in culture. I. Conditions for the appearance of an alteration in glucose 6-phosphate dehydrogenase

Glucose 6-phosphate dehydrogenase has been found to be altered in ageing human fibroblasts in culture. In this article, we have studied the effects of incubation conditions on glucose 6-phosphate dehydrogenase present in isolated cells or homogenates from young and old cells. We show that incubation at 4 degrees C and pH 7.4 induced the appearance of a heat-labile enzyme; this was not the case at pH 6.5. Also NADP+, when present, protects the enzyme from being modified. The kinetics of the modification indicates that the altered form of the enzyme is an intermediary stage between the active and inactive forms. We now have a model system in which the appearance of an altered enzyme can be induced in only a few hours; this model will be used in our next paper to study the mechanism of this alteration.     

Menopause and determinants of quality of life in women at midlife and beyond: the study of health in pomerania (SHIP)

OBJECTIVE: Determinants of quality of life (QoL) in pre- and postmenopausal women including nonhormonal modulators of QoL in adult women are not well understood; there is an ongoing controversy about the impact of menopause on health-related QoL. We investigated the extent to which diverse mental and physical symptoms are associated with (a) menopausal status; (b) sociodemographic, psychosocial, and lifestyle factors; and (c) menopausal hormone therapy (MHT) in adult women after the German reunification in a region of the former German Democratic Republic. DESIGN: The Study of Health in Pomerania is a cross-sectional, population-based survey. Computer-based structured interviews and self-administered questionnaires were used to capture QoL (Zerssen Symptom List) and sociodemographic parameters, psychosocial, and lifestyle indicators (age, socioeconomic status, abuse, social support, nutrition, body mass index, self-rated health, chronic diseases, and use of MHT) in 1,119 pre- and postmenopausal women with an intact uterus. RESULTS: Analyses suggest that menopausal status was not associated with QoL. MHT was associated with physical, mental, and gastrointestinal symptoms. Age was a significant predictor for cardiopulmonary symptoms and sensory impairment. The relationship between age and both physical and mental complaints was inverse as was the relationship between age and both mood and gastrointestinal symptoms. Age, socioeconomic status, physical and sexual abuse, perceived social support, nutrition, body mass index, self-rated health, chronic diseases, and MHT modulated QoL. CONCLUSIONS: Our findings do not support the hypothesis that QoL is reduced after menopause. Differences between pre- and postmenopausal women can be explained by sociodemographic, psychosocial, and lifestyle factors.     

The effects of chemotherapy and long-term gonadotrophin suppression on the ovarian reserve in premenopausal women with breast cancer

BACKGROUND: Reproductive function following cancer treatment is of increasing importance with improving survival rates. We therefore assessed the markers of the ovarian reserve in premenopausal women, to investigate and compare the effects of chemotherapy and long-term gonadotrophin withdrawal on ovarian function. METHODS: Fifty premenopausal (age range 28-52 years) women with early breast cancer were recruited. Serum hormone and ovarian ultrasound measurements were taken before treatment and at intervals up to 1 year during chemotherapy or gonadotrophin suppressive therapy. RESULTS: Pretreatment samples indicated a fall in anti-Müllerian hormone (AMH) concentration with age before changes in other hormone concentrations. AMH concentration showed a rapid and marked fall during chemotherapy, with undetectable concentrations in many women (P<0.0001). Inhibin B concentration showed a lesser fall (P<0.0001), whereas estradiol (E2) concentrations were maintained. Both antral follicle count (AFC) and ovarian volume fell (P<0.0001 and P<0.05 respectively). Regimens containing taxanes in addition to cyclophosphamide showed increased gonadotoxicity. Gonadotrophin suppression resulted in expected falls in E2 (P<0.05) and inhibin B (P<0.001) levels, but also resulted in a delayed fall in AMH level after 6 months (P<0.0001). CONCLUSIONS: These data confirm the value of AMH concentration as an early indicator of ovarian ageing including assessment of chemotherapy-induced ovarian follicle loss. FSH and AMH concentration measurements may be useful for the comparison of ovarian toxicity of different chemotherapy regimens.     

Maternal postpartum stress and toddler developmental delays: Results from a multisite study of racially diverse families

Maternal psychosocial stress during pregnancy can adversely influence child development, but few studies have investigated psychosocial stress during the postpartum period and its association with risk of toddler developmental delays. Moreover, given the expanding diversity of the U.S. population, and well-documented health and stress disparities for racial and ethnic minorities, research examining the effect of postpartum stress on risk of developmental delays in diverse populations is of critical importance. In this study, data from the Community Child Health Network provided the opportunity to test maternal postpartum stress as a predictor of toddler risk of developmental delay in a sample of African American, Latina and non-Hispanic White women and their toddlers (N = 1537) recruited in urban, suburban, and rural communities. Postpartum maternal stress over 1 year was operationalized as perceived stress, life events, and negative impact of life events. Regression results revealed higher risk of developmental delays in toddlers whose mothers experienced more negative life events, greater negative impact of events, and higher perceived stress over the year. Prenatal stress, pregnancy/birth complications, and postpartum depression did not explain these associations. Maternal postpartum stress may contribute to increased risk for developmental delays and is an important target for psychosocial intervention.     

Social support,anxiety and depression after chemotherapy for ovarian cancer: A prospective study

Objectives: We aimed to describe the levels of anxiety and depression in patients during the 3 month period following the end of chemotherapy treatment and to identify factors that predict psychological morbidity. Method: We performed a prospective study in women with ovarian cancer to determine the changes in psychological status in the 3 months following completion of chemotherapy. Sixty‐three consecutive patients were assessed at the completion of chemotherapy (Time 1) and 57 at 3 months follow‐up (Time 2). Relevant disease and patient characteristics were recorded and patients were assessed at Time 1 for anxiety, depression and their perception of emotional support, an index of their psychosocial environment. Anxiety and depression were re‐assessed at Time 2. Results: The results indicate significant initial psychological morbidity, with clinical caseness for anxiety (38%) and depression (33%) being common. Follow‐up at Time 2 shows that patients undergo a significant reduction in cases (19%) and symptoms of depression but an increase in cases of anxiety (47%). The principal factors associated with symptoms of anxiety at Time 2 were poor perceived social support, increased intrusive thoughts and, to a lesser extent, younger age. Medical parameters, such as the stage of disease, response of the cancer to treatment, Ca125 (a tumour glycoprotein) and Karnofsky Performance status (a measure of how well the patients is) were not associated with worse psychological outcome. Conclusion: These data show for the first time that social support and intrusive thoughts, rather than physical parameters, are the principal determinants of psychological morbidity in patients with ovarian cancer.     

Psychosocial intervention for women with primary, non-metastatic breast cancer: a comparison between participants and non-participants

BACKGROUND: Despite improvements in the medical treatment of breast cancer, resulting in better prognoses, women diagnosed with the illness often experience psychosocial problems. As a result, many psychosocial intervention programs have been developed, usually with positive results. The aim of this study was to examine the effects of two 12-week psychosocial intervention programs for women with a primary, non-metastatic breast cancer diagnosis in comparison to women who were on a waiting list for these interventions for 3 months. METHODS: Sixty-nine women with primary, non-metastatic breast cancer, but otherwise without psychosocial problems, were randomized to a group of patients treated with the intervention program (group psychotherapy or social support group) or a control group (on a waiting list). Differences between both groups in psychosocial adjustment, social support and coping at the short-term follow-up were described in this study. RESULTS: Women who participated in the group intervention programs did not differ from women in the control group regarding psychosocial adjustment at the end of the study. Women who participated in the social support groups reported to receive more social support from others not very close to them. They also used more palliative coping than women from the psychotherapy group. CONCLUSIONS: Apparently, women who are being diagnosed with breast cancer, but otherwise have no psychosocial adjustment problems following the diagnosis, do not especially benefit from a short-term intervention program compared to women in the control group.     

Disease perception and social behaviour in persistent rhinitis: a comparison between patients with allergic and nonallergic rhinitis

BACKGROUND: Although the understanding of the pathophysiology and pharmacology of rhinitis has increased within recent years, few studies have examined the impact of rhinitis on patients' behaviour. AIM: To compare perennial allergic rhinitis (PAR) and perennial nonallergic rhinitis (PNR) in terms of patients' perception of their disease and its psychosocial concomitants. METHODS: Thirty-one PAR patients and 32 PNR patients responded to a standard symptom list and were interviewed in-depth regarding their complaints and the impact of rhinitis on their daily lives. RESULTS: PAR and PNR patients reported similar somatic and psychosocial complaints. In both disease groups the adverse effects of rhinitis were reported to be substantially limiting, particularly in social contacts, the impact appearing to be more severe in the women. CONCLUSION: Rhinitis has a severe impact on the daily lives of patients, women reporting more severe psychosocial effects. Disease perception and social adjustment appear to not depend appreciably on whether or not an objective diagnosis of rhinitis can be established.     

The role of psychosocial factors in the course of pain—a 1-year follow-up study among women living in Sweden

The understanding of the associations between psychosocial factors and persistent pain and their impact on the course of pain among women is crucial to identify risk populations and prevent long-term pain from developing. The aim of the study was to investigate the course of pain among women and the psychosocial factors associated with it. The study was a 1-year follow-up (FU) among 2,300 women in the general population of Sweden. Sociodemographic and psychosocial factors were analyzed in relation to the course of pain, assessed as the presence of pain during the last 3 months at baseline (BL) and at FU. Thirty-three percent of the women with no pain at BL and 77% of those with pain at BL reported pain at FU. Compared to the pain-free women, those who developed pain at FU reported lower social support and physical quality of life (QoL) and worse mental health. Women with sustained pain were older and reported worse mental health, lack of social support, and lower levels of QoL compared to those who recovered from pain. In the multiple logistic regression analyses, only post-traumatic stress symptoms were associated with the development of pain at FU. Number of pain locations and pain duration at BL and physical QoL were associated with sustained pain. Moreover, social support was identified as a protective factor against sustained pain. Pain is persistent or recurrent in a general female population. The results indicate that psychosocial factors do not work as primary predictors in the course of pain and might be better understood through indirect processes by limiting the individual’s resources for handling pain in a functional manner.     

Clinical experience with patients suffering from hyperemesis gravidarum (severe nausea and vomiting during pregnancy): thoughts about subtyping of patients,treatment and counseling models

The medical and psychological treatment of hyperemesis gravidarum (HG) is generally acknowledged as being difficult. It is also recognized that the somatic changes during pregnancy play a role in the process of HG and that psychosocial factors are of particular importance. The following issues have been studied: psychosocial stressors; personality disorders; coping mechanisms and stress tolerance. The reviewed studies mention many different causes of HG. Some produce symptoms in certain women and some will not. As a result of clinical experience and observation during several years treating women with HG from a broad social, cultural and ethnic background in a large inner-city general hospital, we have been able to identify several subgroups of HG patients according to personality pathology, psychiatric symptoms and psychosocial stress factors. Accurate assessment is necessary in order to be able to tailor the interventions to the characteristics and needs of the individual patient. For the various subgroups different treatment strategies are recommended.     

How patients deal with an ambiguous medical test: Decision-making after genetic testing

ObjectiveWe know little about how patients make decisions when they receive a variant of uncertain significance result (VUS) from genetic testing. The purpose of this study was to elucidate a model of patient-informed decision-making after receiving a VUS result.MethodsUsing an adapted Mental Models Approach, we conducted semi-structured interviews with women who received a VUS result from genetic testing for hereditary breast cancer (N = 20) to explore factors they believed were relevant to their decision-making. Two coders used a coding scheme informed by experts in hereditary breast cancer to conduct analysis. Inter-coder reliability was α = .86.ResultsThree overarching decision themes emerged from the interviews: managing ambiguity, medical risk management, and sharing results with others. While participants noted some difficulty understanding their result, genetic counselors’ interpretations, psychosocial factors (e.g., risk perceptions), and competing extrinsic demands influenced their decisions.ConclusionComplex influences affect patient decision-making after a VUS result from genetic testing and may encourage health protective behavior.Practice ImplicationsEven patients who understand their test result could use support managing the ambiguity of their test result and sharing it with others.     

How has body image changed? A cross-sectional investigation of college women and men from 1983 to 2001

Body-image dissatisfaction is not uncommon and can adversely affect individuals' psychosocial functioning and quality of life. Various oft-cited surveys and a meta-analysis implicate a worsening of body image over the past several decades, especially among women and possibly among men. The present cross-sectional study examined changes in multiple facets of body image among 3,127 college students from 1983 through 2001; the same standardized assessment was used in 22 studies conducted within the same university. Results confirmed non-Black women's increasing body-image dissatisfaction until the early or mid-1990s, after which significant improvements occurred in terms of overall body-image evaluation and overweight preoccupation among both non-Black and Black women, despite heavier body weights. A reduction over time in women's investment in their appearance was also evident. Men's body image was relatively stable during the 19-year period. Explanations, limitations, and implications of the findings are discussed.