Autoimmune lymphoproliferative syndrome

Autoimmune lymphoproliferative syndrome arises early in childhood in people who inherit mutations in genes that mediate lymphocyte apoptosis, or programmed cell death. In the immune system, antigen-induced lymphocyte apoptosis maintains immune homeostasis by limiting lymphocyte accumulation and minimizing reactions against self-antigens. In autoimmune lymphoproliferative syndrome, defective lymphocyte apoptosis manifests as chronic, nonmalignant adenopathy and splenomegaly; the expansion of an unusual population of CD4-CD8- T cells; and the development of autoimmune disease. Most cases of autoimmune lymphoproliferative syndrome involve heterozygous mutations in the lymphocyte surface protein Fas (CD95, Apo1) that impair a major apoptotic pathway. Prospective evaluations of patients and their families have revealed an ever-expanding spectrum of autoimmune lymphoproliferative syndrome and its major complications.     

Sentenced to treatment: early experience of drug treatment and testing orders in England

Drug Treatment and Testing Orders (DTTOs) were introduced in the 1998 Crime and Disorder Bill and were piloted in three areas in England over the subsequent 18 months. The orders, funded by the Home Office, allow drug using offenders to be coerced into attending for treatment, to have regular urine tests and to be reviewed by the courts. In Croydon an equal partnership was set up between probation, a local statutory provider of drug services and a voluntary sector agency. Treatment plans were individualised and included a variety of treatment options. Forty-eight orders were imposed mainly for persistent shoplifting. Sixty-three percent of individuals had used heroin and 54% crack cocaine in the 30 days before the order was imposed. Ethical issues raised in coerced treatment were important for the individuals providing treatment although the clients all had to consent to treatment. The pilot programme raised issues about the nature of treatment, clinical responsibility, the selection of clients for orders and the objectives of treatment. Frequent urine testing was problematic but in the vast majority of cases clients were not breached just because of positive tests. The provision of DTTOs in an area created unacceptable inequalities in access to treatment. The paper concludes that partnership working and clear objectives are vital for treatment programmes to operate effectively. More research is needed to explore the most optimum way to deliver treatment in the context of a DTTO.     

Written language clues to cognitive changes of aging: an analysis of the letters of King James VI/I

Reductions in language complexity normally occur in older adults because of decreased working memory and rate of language processing. Comparative measures can reveal whether linguistic change is due to normal aging or dementia. Linguistic analysis of a series of letters of King James, 1566-1625, investigate whether he exhibited a normative or atypical pattern of change. Fifty-seven letters from the years 1604 to 1624 were analyzed. Data modeling reveals a quadratic pattern of decline in written language complexity with increased diversity of vocabulary corresponding to historical reports of illness around 1618-1619. This investigation demonstrates how language analysis can provide valuable insight to normal and pathological cognitive changes of aging as well as to the understanding of historical figures.     

Evaluation of educational programs in inflammatory bowel disease

BACKGROUND: Little is known about the status of patient knowledge in inflammatory bowel disease (IBD) and potential benefit of educational programs. The authors conducted this study to assess 1) the knowledge of IBD of participants attending educational workshops offered to the public and 2) the effect of the workshop on participants' knowledge level. METHODS: Workshops on IBD were offered to the public at nine communities in the United States. Each workshop consisted of a combination of 3 hours of presentations and question-and-answer sessions. Participants, including patients with IBD and their parents, spouses, siblings, friends, and significant others, were asked to complete the Crohn's and Colitis Knowledge Score questionnaires just before (Q1) and immediately after (Q2) the workshop and approximately 3 months later (Q3). The authors scored one point for each correct answer to the 30 questions in the Crohn's and Colitis Knowledge Score. RESULTS: Of the 734 who completed the Q1, 33.7% gave correct answers for questions about IBD complications, 36.2% for treatment, 61.4% for general knowledge, and 64.8% for diet. After the workshop, the proportion for these four knowledge areas increased by 11.0% to 19%. For the participants who completed all of the three questionnaires and answered all the 30 questions (N=59), the mean score was 18 at Q1, 22 at Q2 (p<0.001, Q2 vs. Q1), and 21 at Q3 (p<0.001, Q3 vs. Q1). CONCLUSIONS: The public's general knowledge of IBD is low. Educational programs oriented toward IBD improve participant's knowledge, and the knowledge they acquired is retained for at least 3 months.     

Estrogen and antiestrogen regulation of cell cycle progression in breast cancer cells

The central involvement of estrogen in the development of the mammary gland and in the genesis of breast cancer has lent impetus to studies of the links between estrogen action and the cell cycle machinery. Recent studies of the estrogenic regulation of molecules with known roles in the control of G1/S phase progression have resulted in significant advances in understanding these links. Estrogens independently regulate the expression and function of c-Myc and cyclin D1 and the induction of either c-Myc or cyclin D1 is sufficient to recapitulate the effects of estrogen on cell cycle progression. These pathways converge at the activation of cyclin E-Cdk2 complexes. The active cyclin E-Cdk2 complexes are depleted of the cyclin dependent kinase (CDK) inhibitor p21(WAF1/CIP1) because of estrogen-mediated inhibition of nascent p21(WAF1/CIP1). Insulin and estrogen synergistically stimulate cell cycle progression, and the ability of estrogen to antagonize an insulin-induced increase in p21(WAF1/CIP1) gene expression appears to underlie this effect. Antiestrogen treatment of MCF-7 cells leads to an acute decrease of c-Myc expression, a subsequent decline in cyclin D1, and ultimately arrest of cells in a state with features characteristic of quiescence. An antisense-mediated decrease in c-Myc expression results in decreased cyclin D1 expression and inhibition of DNA synthesis, mimicking the effects of antiestrogen treatment and emphasizing the importance of c-Myc as an estrogen/antiestrogen target. These data identify c-Myc, cyclin D1, p21(WAF1/CIP1) and cyclin E-Cdk2 as central components of estrogen regulation of cell cycle progression and hence as potential downstream targets that contribute to the role of estrogen in oncogenesis.     

Experience with the use of an iron polymaltose (dextrin) complex given by single total dose infusion to stable chronic haemodialysis patients

BACKGROUND/AIM: Investigators have reported that the nonmuscle myosin heavy chain B (SMemb) expression is enhanced in various types of glomerular diseases which develop into nephrosclerosis. In renal transplantation, transplant glomerulitis is often recognized during acute rejection. Therefore, we hypothesized that SMemb plays important roles in acute kidney rejection. To evaluate the role of SMemb in the development of kidney rejection, we examined its expression in rat kidney transplantation models. METHODS: We used Lewis rats as recipients and Wistar rats as donors. Group I: controls; group II: isograft model; group III: allograft model; group IV: as group III +10 mg/kg/day of ciclosporin A (CsA), and group V: as group III + CsA administration for 5 days postoperatively. Histopathological and SMemb immunohistochemical studies were completed. RESULTS: Clear enhancement of SMemb expression was found on day 3 in group III. In groups I, II, IV, and V, SMemb was faintly expressed in the glomerular cells. However, after termination of CsA treatment, the SMemb expression increased. The expression of SMemb was higher in the allograft model than in either isograft or CsA-treated models. CONCLUSIONS: Immunohistological investigations show that the SMemb expression was significant from an early stage at which histopathological reactions were hardly identifiable. This, therefore, could be useful for an earlier diagnosis of acute rejection.