Effect of insulin-like growth factor I on HIV type 1 long terminal repeat-driven chloramphenicol acetyltransferase expression

In this study, we have investigated the ability of insulin-like growth factor I (IGF-I) to inhibit HIV long terminal repeat (LTR)-driven gene expression. Using COS 7 cells cotransfected with tat and an HIV LTR linked to a chloramphenicol acetyltransferase (CAT) reporter, we observed that physiological levels of IGF-I (10-9 M) significantly inhibited CAT expression in a concentration- and time-dependent manner. IGF-I did not inhibit C AT expression in COS 7 cells transfected with pSVCAT, and did not affect CAT expression in the absence of cotransfection with tat . Transfection of HIV-1 proviral DNA into COS 7 cells +/- IGF-I resulted in a significant decrease ( p 0.05) in infectious virion production. Both IGF-I and Ro24-7429 inhibited LTR-driven C AT expression, while TNF- alpha -enhanced CAT expression was not affected by IGF-I. On the other hand, a plasmid encoding parathyroid hormone-related peptide exhibited dramatic additivity of inhibition of CAT expression in COS 7 cells. Finally, we show that in Jurkat or U937 cells cotransfected with HIVLTRCAT/tat, IGF-I significantly inhibited CAT expression. Further, interleukin 4 showed in U937 cells inhibition of CAT expression that was not additive to IGF-I induced inhibition. Our data demonstrate that IGF-I can specifically inhibit HIVLTRCAT expression. This inhibition may occur at the level of the tat /TAR interaction. Finally, this IGF-I effect is seen in target cell lines and similar paths of inhibition may be involved in the various cell types employed.

Blocking semiovals of Type (1,M+1,N+1)

We consider the existence of blocking semiovals in finite projective planes which have intersection sizes 1, m+1 or n+1 with the lines of the plane for $1 \leq m < n$. For those prime powers $q \leq 1024$, in almost all cases, we are able to show that, apart from a trivial example, no such blocking semioval exists in a projective plane of order q. We are also able to prove, for general q, that if q2+q+1 is a prime or three times a prime, then only the same trivial example can exist in a projective plane of order q.

Health-related quality of life and metabolic control in children with type 1 diabetes : a prospective cohort study

OBJECTIVE—To assess change in health-related quality of life (HRQOL) in children with diabetes over 2 years and determine its relationship to change in metabolic control.

RESEARCH DESIGN AND METHODS—In 1998, parents of children aged 5–18 years attending a tertiary diabetes clinic reported their child’s HRQOL using the Child Health Questionnaire PF-50. Those aged 12–18 years also self-reported their HRQOL using the analogous Child Health Questionnaire CF-80. HbA_1c levels were recorded. In 2000, identical measures were collected for those who were aged ≤18 years and still attending the clinic.

RESULTS—Of 117 eligible subjects, 83 (71%) participated. Parents reported no significant difference in children’s HRQOL at baseline and follow-up. However, adolescents reported significant improvements on the Family Activities (P < 0.001), Bodily Pain (P = 0.04), and General Health Perceptions (P = 0.001) scales and worsening on the Behavior (P = 0.04) scale. HbA1c at baseline and follow-up were strongly correlated (r = 0.57). HbA_1c increased significantly (mean 7.8% in 1998 vs. 8.5% in 2000; P < 0.001), with lower baseline HbA_1c strongly predicting an increase in HbA_1c over the 2 years (r² = 0.25, P < 0.001). Lower parent-reported Physical Summary and adolescent-reported Physical Functioning scores at baseline also predicted increasing HbA_1c. Poorer parent-reported Psychosocial Summary scores were related to higher HbA_1c at both times but did not predict change in HbA_1c.

CONCLUSIONS—Changes in parent and adolescent reports of HRQOL differ. Better physical functioning may protect against deteriorating HbA_1c, at least in the medium term. While the HRQOL of children with diabetes does not appear to deteriorate over time, we should not be complacent, as it is consistently poorer than that of their healthy peers.

Young women with type 1 diabetes' management of turning points and transitions

The authors used grounded theory to explore and develop a substantive theory to explain how 20 young women with type 1 diabetes managed their lives when facing turning points and undergoing transitions. The women experienced a basic social problem: being in the grip of blood glucose levels (BGLs), which consisted of three categories: (a) the impact of being susceptible to fluctuating BGLs, (b) the responses of other people to the individual woman’s diabetes, and (c) the impact of the individual women’s diabetes on other people’s lives. The women used a basic social process to overcome the basic social problem by creating stability, which involved using three interconnected subprocesses: forming meaningful
relationships, enhancing attentiveness to blood glucose levels, and putting things in perspective. Insights into the processes and strategies used by the women have important implications for provision of care and service delivery.

Disease fingerprinting with cDNA microarrays reveals distinct gene expression profiles in lethal type 1 and type 2 cytokine-mediated inflammatory reactions

Development of polarized immune responses controls resistance and susceptibility to many microorganisms. However, studies of several infectious, allergic, and autoimmune diseases have shown that chronic type-1 and type-2 cytokine responses can also cause significant morbidity and mortality if left unchecked. We used mouse cDNA microarrays to molecularly phenotype the gene expression patterns that characterize two disparate but equally lethal forms of liver pathology that develop in Schistosoma mansoni infected mice polarized for type-1 and type-2 cytokine responses. Hierarchical clustering analysis identified at least three groups of genes associated with a polarized type-2 response and two linked with an extreme type-1 cytokine phenotype. Predictions about liver fibrosis,  apoptosis, and granulocyte recruitment and activation generated by the microarray studies were confirmed later by traditional biological assays. The data show that cDNA microarrays are useful not only for determining  coordinated gene expression profiles but are also highly effective for molecularly “fingerprinting” diseased tissues. Moreover, they illustrate the potential of genome-wide approaches for generating comprehensive views on the molecular and biochemical mechanisms regulating infectious  disease pathogenesis.

The mother-daughter guilt dynamic : effects of type 1 diabetes during life transitions

Aim. The aim of the study was to explore and describe the strategies young women with type 1 diabetes used to manage life transitions. The paper describes one aspect of how guilt dynamic often operates between mothers and daughters and how the women managed the guilt dynamic to create stability in their lives.
Background. When a child is diagnosed with diabetes, major transitional changes occur in the relationships between the mother and her child. The changes affect the psychological and social aspects of their lives and have a major impact on how young women manage their diabetes. A guilt dynamic between mothers and young women with diabetes emerged as a major theme in a larger study that investigated how young women with diabetes managed life transitions. Although the literature indicates that mothers of chronically ill children experience guilt feelings towards their children, little research was identified that addressed the emotional dynamics between mothers and daughters with diabetes.
Design. Using grounded theory method, interviews were conducted with 20 women with type 1 diabetes and five mothers during 2002 and 2003. Constant comparative analysis was used to analyse the data and develop an in-depth understanding of the experience of living with diabetes during life transitions.
Findings. The findings revealed that guilt feelings created a two-way dependency between mothers and their daughters with diabetes. The two-way dependency involved feelings of being a burden to each other, difficulty balancing responsibilities for diabetes management, difficulty relinquishing emotional and social dependency especially during life transitions. In addition, these issues were rarely discussed openly with each other or with health professionals. The findings provide additional information about the human experience of the mother–daughter relationship and the effect on coping with diabetes in the context of life transitions.
Conclusions. Understanding the impact diabetes has on the emotional and social well being of both women with type 1 diabetes and their mothers is critical in planning appropriate support for both groups. Most importantly, it is critical to understand the guilt dynamic that operates during young women with diabetes' life transitions when the daughters' dependency on their mother's control and responsibility for diabetes management undergo changes resulting in emotional responses, especially guilt feelings.
Relevance to clinical practice. Health professionals need to understand the emotional and social impact of the guilt dynamics between young women with type 1 diabetes and their mothers. Adequate and appropriate support can minimize the guilt feelings and enhance stability and quality of life for both mothers and their daughters, especially during major life transitions, such as motherhood.

Transitions : experiences of women with type 1 diabetes : Turning points and transitions as experienced by young women with type 1 diabetes in Australia

The relationship among psychosocial stress, coping and metabolic control has a key effect on diabetes clinical outcomes and mental health. Life transitions are peak times of major change within personal and social contexts, which add stress affecting on peoples? problem solving. The thesis describes young women with Type 1 diabetes? perspectives of the problems encountered and how they managed them when they faced turning points and made life transitions. The study identified the women?s health concerns and factors that enhanced or hindered their ability to manage turning points and transitions. A substantive theory that comprised a problem of ?being in the grip of blood glucose levels? (BGLs) and a process termed ?creating stability? to manage life transitions was developed. The state of being in the grip of BGLs was associated with the impact of fluctuating BGLs; responses of other people to the womens? diabetes and the impact of diabetes on other people?s lives. The women managed these problems by engaging in social and psychological strategies helping them to stabilised their lives and feel more in control during life transitions.

Psychological impact of DAFNE training in adults with Type 1 diabetes

This thesis investigated the psychological impact of an education intervention, Dose Adjustment for Normal Eating (DAFNE), in adults with type 1 diabetes. The results demonstrated that the education programme improved participants' subjective wellbeing, self-efficacy and reduced diabetes-related distress compared to a comparison group that engaged in usual care. The portfolio examined the use of mindfulness-based strategies, in particular Acceptance and Commitment Therapy (ACT) in four case studies which illustrated that the impact of the therapy is directly related to the the willingness of the client to engage in the practices.

Turning points and transitions : experiences of young women with Type 1 diabetes

This research explores young women with Type 1 diabetes' perspectives of the problems and how they manage them when facing turning points and making life transitions. The study presents a substantive theory of how the women tried to minimise the grip of blood glucose levels felt during transitions by creating stability in their lives.

Young adults’ management of Type 1 diabetes during life transitions

Aim. To identify life transitions likely to impact diabetes self-care among young adults with Type 1 diabetes and their coping strategies during transition events.
Background. Relationships among psychosocial stress, adjustment, coping and metabolic control affect clinical outcomes and mental health. Life transitions represent major change and are associated with stress that temporarily affects individuals’ problem-solving, coping abilities and blood glucose levels.
Design. A qualitative interpretive inquiry.
Method. Semi-structured interviews were conducted with 20 young adults with Type 1 diabetes and a constant comparative analysis method. Data and analysis was managed using QSR NVIVO 7 software.
Results. Participants identified two significant transition groups: life development associated with adolescence, going through the education system, entering new relationships, motherhood and the workforce and relocating. Diabetes-related transitions included being diagnosed, developing diabetes complications, commencing insulin pump treatment and going on diabetes camps. Participants managed transitions using ‘strategic thinking and planning’ with strategies of ‘self-negotiation to minimise risks’; ‘managing diabetes using previous experiences’; ‘connecting with others with diabetes’; ‘actively seeing information to ‘patch’ knowledge gaps’; and ‘putting diabetes into perspective’.
Conclusions. Several strategies are used to manage diabetes during transitions. Thinking and planning strategically was integral to glycaemic control and managing transitions. The impact of transitions on diabetes needs to be explored in larger and longitudinal studies to identify concrete strategies that assist diabetes care during life transitions.
Relevance to clinical practice. It is important for health professionals to understand the emotional, social and cognitive factors operating during transitions to assist young adults with Type 1 diabetes to achieve good health outcomes by prioritising goals and plan flexible, timely, individualised and collaborative treatment.