Cross-species characterization of the ALS2 gene and analysis of its pattern of expression in development and adulthood

Mutations in the ALS2 gene, which encodes alsin, cause autosomal recessive juvenile-onset amyotrophic lateral sclerosis (ALS2) and related conditions. Using both a novel monoclonal antibody and LacZ knock-in mice, we demonstrate that alsin is widely expressed in neurons of the CNS, including the cortex, brain stem and motor neurons of the spinal cord. Interestingly, the highest levels of alsin are found in the molecular layer of the cerebellum, a brain region not previously implicated in ALS2. During development, alsin is expressed by day E9.5, but CNS expression does not become predominant until early postnatal life. At the subcellular level, alsin is tightly associated with endosomal membranes and is likely to be part of a large protein complex that may include the actin cytoskeleton. ALS2 is present in primates, rodents, fish and flies, but not in the nematode worm or yeast, and is more highly conserved than expected among mammals. Additionally, the product of a second, widely expressed gene, ALS2 C-terminal like (ALS2CL), may subserve or modulate some of the functions of alsin as an activator of Rab and Rho GTPases.     

Colon microflora in infants fed formula with galacto- and fructo-oligosaccharides: more like breast-fed infants

OBJECTIVES: The intestinal flora of breast-fed infants is generally dominated by Bifidobacteria. We aimed to investigate whether an infant formula supplemented with galacto-oligosaccharides and fructo-oligosaccharides (GOS/FOS) is able to establish a bifido-dominant microflora, not only in numbers but also with respect to the metabolic activity in the colon. METHODS: Two groups of infants fed infant formula with 0.8 g/100 ml GOS/FOS in a ratio of 9:1 (OSF group), or control formula (SF group) were evaluated in a randomised, double blind, placebo controlled intervention study. A breast-fed group was studied in parallel. At study onset and after 4 and 6 weeks, faecal samples were examined for the number of bifidobacteria, pH, short chain fatty acids and lactate. RESULTS: After 6 weeks, the mean proportion of bifidobacteria was significantly higher in the OSF group (59.6% versus 49.5% in the SF group; P < 0.05). Compared with controls, infants in the OSF group had a lower stool mean pH and an increased proportion of acetate and a decreased proportion of propionate. The mean pH in the OSF and SF groups were 5.7 and 6.3, respectively (P < 0.001). CONCLUSIONS: The addition of the prebiotic GOS/FOS mixture to an infant formula has a stimulating effect on the growth of bifidobacteria and on the metabolic activity of the total intestinal flora. The changes in short chain fatty acids, lactate and pH in the prebiotic group represent a fermentation profile that is closer to that observed in breast-fed infants compared to infants fed control formula.     

Intralesional immunotherapy of warts with mumps, Candida, and Trichophyton skin test antigens: a single-blinded, randomized, and controlled trial

BACKGROUND: Warts occur commonly in humans. Destructive modalities are generally the first physician-administered therapy. Other treatment options include immunotherapy. Intralesional immunotherapy using mumps, Candida, or Trichophyton skin test antigens has proved efficacy in the treatment of warts. OBJECTIVES: To determine rates of wart resolution in response to injection of antigen alone, antigen plus interferon alfa-2b, interferon alfa-2b alone, and normal saline; and to compare response according to viral type, major histocompatibility complex antigens, and peripheral blood mononuclear cell proliferation to autologous human papillomavirus antigen before and after injection. DESIGN: Randomized, single-blinded, placebo-controlled, clinical trial. SETTING: Medical school-based dermatology department. PATIENTS: Two hundred thirty-three patients clinically diagnosed as having 1 or more warts.Main Outcome Measure Clinical resolution of warts in response to intralesional immunotherapy. RESULTS: Responders were observed in all treatment arms, but were significantly more likely to have received antigen (P<.001). Resolution of distant untreated warts was observed, and was significantly more likely in subjects receiving antigen (P<.001). Interferon did not significantly enhance the response rate (P = .20) and did not differ from normal saline (P = .65). No viral type or major histocompatibility complex antigen correlated with response or lack of response (P>.99 and P = .86, respectively). A positive peripheral blood mononuclear cell proliferation assay result (2 times pretreatment levels) was significantly more likely among responders (P = .002). While there was no significant difference in response based on sex (P = .56), older subjects (>40 years) were less likely to respond (P = .01). CONCLUSIONS: Intralesional immunotherapy using injection of Candida, mumps, or Trichophyton skin test antigens is an effective treatment for warts, as indicated by significantly higher response rates and distant response rates in subjects receiving antigen. Viral type and major histocompatibility complex antigens did not seem to influence treatment response. Response is accompanied by proliferation of peripheral blood mononuclear cells to human papillomavirus antigens, suggesting that a human papillomavirus-directed cell-mediated immune response plays a role in wart resolution.     

Basic immunology: a primer

This article is intended to bring practicing physicians up to date on the current state of knowledge regarding the basic components and processes of the immune system. It discusses the role of the immune system and the importance of self-tolerance and describes the main cellular and noncellular entities involved in the immune response. It also details immune processes such as the lymphocyte selection process leading to self tolerance; antigen processing and presentation; cell signaling, activation, and co-stimulation; and the actions of cytokines and other signaling molecules.     

Pemphigus, pregnancy, and plasmapheresis

Pemphigus vulgaris (PV) is an autoimmune blistering disorder that usually occurs in the fifth and sixth decades of life but may occur at younger ages and during pregnancy. Circulating intercellular antibodies directed at desmosomal proteins may cross the placenta and place children at risk for neonatal pemphigus (NP). We describe the case of a pregnant woman with PV treated successfully with a combination of systemic corticosteroids and plasmapheresis. The possibility of PV should be considered in any pregnant woman with a worsening, widespread, mucocutaneous, blistering disease. Plasmapheresis offers a useful alternative to immunosuppressive therapy in the setting of pregnancy.     

Intraoperative surgical complication during cesarean section: an observational study of the incidence and risk factors

BACKGROUND: The study was intended to estimate the incidence of intraoperative surgical complications with the impact of the educational level of the surgeon and a history of previous cesarean section on intraoperative complications at cesarean childbirth. METHODS: In the period between August 1st 1995 and July 30th 1996, 7782 women gave birth at the three Obstetric Departments in Copenhagen County, Denmark, of which 929 (11.9%) were delivered by cesarean section. These women served as the study population, and their medical records were reviewed and data obtained immediately after delivery. RESULTS: The overall intraoperative complication rate was 12.1%. The rate of complications in emergency cesarean sections was 14.5% compared with 6.8% in the elective group. The educational level of the surgeon and a history of previous cesarean section were not found to be significantly associated to intraoperative complications. Low station of the presenting part of the fetus, high fetal birth weight, fetal distress and dystocia as indications and increasing maternal age were significant risk factors of lacerations. Placenta previa and placental abruption as indications, increasing prepregnancy body mass index, as well as low and high birth weight were significant risk factors for intraoperative blood loss more than 1 l. Duration of regular painful contractions had a preventive effect. CONCLUSION: Utero-cervical lacerations and blood loss of more than 1 l were the most frequent intraoperative complications in cesarean section in the present study. The educational level of the surgeon or history of a previous cesarean section were not significantly related to these complications.     

Focused expressive writing as self-help for stress and trauma

In the therapy process, the process of disclosing about stressful or traumatic events is often considered essential. One such manner is through focused expressive writing (FEW) about stressful or traumatic experiences. FEW is related to improvements in health and well-being, across a wide array of outcomes and participant characteristics. As FEW requires limited involvement of other individuals, is relatively low cost, and portable, it has tremendous potential as self-help. In particular, FEW may be an effective means to reach populations unwilling or unable to engage in psychotherapy. A case illustration of FEW is presented. Evidence and future directions for FEW as self-help are reviewed.