Upregulation of TGF-beta, FOXP3, and CD4+CD25+ regulatory T cells correlates with more rapid parasite growth in human malaria infection

Understanding the regulation of immune responses is central for control of autoimmune and infectious disease. In murine models of autoimmunity and chronic inflammatory disease, potent regulatory T lymphocytes have recently been characterized. Despite an explosion of interest in these cells, their relevance to human disease has been uncertain. In a longitudinal study of malaria sporozoite infection via the natural route, we provide evidence that regulatory T cells have modifying effects on blood-stage infection in vivo in humans. Cells with the characteristics of regulatory T cells are rapidly induced following blood-stage infection and are associated with a burst of TGF-beta production, decreased proinflammatory cytokine production, and decreased antigen-specific immune responses. Both the production of TGF-beta and the presence of CD4+CD25+FOXP3+ regulatory T cells are associated with higher rates of parasite growth in vivo. P. falciparum-mediated induction of regulatory T cells may represent a parasite-specific virulence factor.     

Adoptive immunotherapy for posttransplantation viral infections.

Viral diseases are a major cause of morbidity and mortality after hemopoietic stem cell transplantation. Because viral complications in these patients are clearly associated with the lack of recovery of virus-specific cellular immune responses, reconstitution of the host with in vitro expanded cytotoxic T lymphocytes is a potential approach to prevent and treat these diseases. Initial clinical studies of cytomegalovirus and Epstein-Barr virus in human stem cell transplant patients have shown that adoptively transferred donor-derived virus-specific T cells may restore protective immunity and control established infections. Preclinical studies are evaluating this approach for other viruses while strategies for generating T cells specific for multiple viruses to provide broader protection are being evaluated in clinical trials. The use of genetically modified T cells or the use of newer suicide genes may result in improved safety and efficacy.     

Autoimmune hepatitis associated with the use of black cohosh: a case study

Herbal remedies generate more than 1.8 billion dollars in annual sales in the United States. Herbal products have been associated with a wide spectrum of hepatic toxicities. With the recent Women's Health Initiative Study demonstrating increased risk of breast cancer and cardiovascular events associated with hormone therapy, many women may resort to herbal remedies for persistent menopause symptoms. We report a case of autoimmune hepatitis likely triggered by the use of black cohosh (Actaea racemosa), an agent marketed to treat menopause symptoms. Given this case report, we recommend close monitoring of women using this herbal preparation.     

Human TLR-7-, -8-, and -9-mediated induction of IFN-alpha/beta and -lambda Is IRAK-4 dependent and redundant for protective immunity to viruses

Five TLRs are thought to play an important role in antiviral immunity, sensing viral products and inducing IFN-alpha/beta and -lambda. Surprisingly, patients with a defect of IRAK-4, a critical kinase downstream from TLRs, are resistant to common viruses. We show here that IFN-alpha/beta and -lambda induction via TLR-7, TLR-8, and TLR-9 was abolished in IRAK-4-deficient blood cells. In contrast, IFN-alpha/beta and -lambda were induced normally by TLR-3 and TLR-4 agonists. Moreover, IFN-beta and -lambda were normally induced by TLR-3 agonists and viruses in IRAK-4-deficient fibroblasts. We further show that IFN-alpha/beta and -lambda production in response to 9 of 11 viruses tested was normal or weakly affected in IRAK-4-deficient blood cells. Thus, IRAK-4-deficient patients may control viral infections by TLR-3- and TLR-4-dependent and/or TLR-independent production of IFNs. The TLR-7-, TLR-8-, and TLR-9-dependent induction of IFN-alpha/beta and -lambda is strictly IRAK-4 dependent and paradoxically redundant for protective immunity to most viruses in humans.     

Treatments of pelvic girdle pain in pregnant women: adverse effects of standard treatment,acupuncture and stabilising exercises on the pregnancy,mother, delivery and the fetus/neonate

Background  

Previous publications indicate that acupuncture is efficient for the treatment of pelvic girdle pain, PGP, in pregnant women. However, the use of acupuncture for PGP is rare due to insufficient documentation of adverse effects of this treatment in this specific condition. The aim of the present work was to assess adverse effects of acupuncture on the pregnancy, mother, delivery and the fetus/neonate in comparison with women that received stabilising exercises as adjunct to standard treatment or standard treatment alone.     

Belief in the harmfulness of antidepressants: results from a national survey of the Australian public

BACKGROUND: Surveys of the public in several countries have found that negative attitudes towards antidepressants are common. However, there has been little research into the factors associated with these attitudes. METHODS: A national survey of 999 Australian adults assessed beliefs about the helpfulness or harmfulness of antidepressants for a person with depression and suicidal thoughts. Associated factors investigated were as follows: sociodemographic characteristics, exposure to depression, ability to recognize depression, beliefs about other depression interventions, beliefs about long-term outcomes with and without treatment, beliefs about causes, and stigmatizing attitudes. RESULTS: Around a quarter of Australian adults believe that antidepressants would be harmful for a person who is depressed and suicidal. This group was less educated, had less exposure to depression, showed poorer recognition of depression, was less favorable about other standard interventions including psychological ones, was less pessimistic about the long-term outcome if the person did not have treatment, and was more likely to see depression as due to weakness and to be under the individual's control. LIMITATIONS: The survey did not directly ask about reasons for believing that antidepressants would be harmful. CONCLUSIONS: Belief in the harmfulness of antidepressants is associated with a general lack of exposure to depression, leading to an underestimation of its seriousness and of the necessity for intervention.     

Genetic linkage analysis identifies new proximal and distal flanking markers for the X-linked agammaglobulinemia gene locus, refining its localization in Xq22

Genetic linkage analysis has been instrumental in mapping thegene for X-linked agammaglobulinemia (XLA) to the proximal longarm of the human X chromosome, to Xq22. Due to the relativerarity of this disease the localization of the gene within Xq22has remained imprecise. We have investigated twenty-nine familiesaffected by XLA and have found no recombinants with the DXS178locus in over 30 informative meioses. DXS178 is now the mostreliable and informative locus for use in pre-natal diagnosisand carrier detection of XLA. In addition, we have identifiednew closely linked proximal and distal flanking markers forXLA, DXS442 and DXS101, respectively. These loci are separatedby 2cM, considerably reducing the extent of DNA within whichthe XLA locus can be contained. This will open up the way formore directed positional cloning efforts for the isolation ofthe XLA gene.