Rapid development of severe hyperplastic gastritis with gastric epithelial dedifferentiation in Helicobacter felis-infected IL-10(-/-) mice.

Interleukin (IL)-10 is a potent anti-inflammatory and immune-regulatory cytokine. Mice deficient in IL-10 production (IL-10(-/-)) develop a spontaneous inflammatory bowel disease, indicating that IL-10 is an important regulator of the mucosal immune response in vivo. To study the role of IL-10 in the host response to gastric Helicobacter infection, stomachs of IL-10(-/-) and wild-type mice were colonized with Helicobacter felis, as a model of human H. pylori infection. Within 4 weeks of H. felis infection, wild-type mice develop a mild, focal chronic gastritis. In contrast, H. felis-infected IL-10(-/-) mice develop a severe hyperplastic gastritis, characterized by a dense, predominantly mononuclear cell inflammation of the mucosa and submucosa and epithelial cell proliferation and dedifferentiation. Within 4 weeks of H. felis infection, there are striking alterations in the character of the gastric epithelium from IL-10(-/-) mice, including a profound loss of parietal and chief cells, focal de novo production of acidic mucins, and marked epithelial proliferation with disordered epithelial architecture. These findings indicate that, in the absence of IL-10, the inflammatory and immunological responses of the murine host to gastric colonization with Helicobacter is a rapidly evolving pathological process with features that mimic those associated with H. pylori infection in humans. H. felis-infected IL-10(-/-) mice may provide a model with which to investigate the cellular and molecular changes that stem from gastric infection with H. pylori.     

Skin testing and extrinsic allergic alveolitis

Skin testing with six common allergens, tuberculin and a sterile avian antigen preparation from pigeon serum was performed on 102 pigeon fanciers. The incidence of positive prick tests to common allergens was no different for subjects with extrinsic allergic alveolitis. EAA, caused by avian exposure than the whole group. Positive immediate weal and flare reactions following skin prick testing with avian antigen occurred in 22 subjects and was closely correlated with atopy. However, when the same antigen was administered intradermally, 69 subjects developed an immediate (15 min) weal and flare reaction which did not correlate with atopy, instead, the weal diameter correlated significantly with the serum IgG antibody titre against pigeon serum gamma-globulin antigen, and furthermore, the higher grades of reaction were highly selective for subjects with EAA. Ten subjects, all with strong early intradermal skin reactions, developed a late (4-6 h) skin reaction; this was again highly selective for EAA. The subjects with cutaneous anergy to tuberculin had markedly higher IgG antibody titres to avian antigens, and these included the majority of the subjects with alveolitis.     

Candida-specific cell-mediated immunity is demonstrable in mice with experimental vaginal candidiasis.

Women with recurrent vulvovaginal candidiasis often demonstrate a down-regulation of cell-mediated immunity (CMI) to Candida albicans detected by a lack of cutaneous delayed-type hypersensitivity (DTH) to Candida antigens. However, the role of systemic CMI as a host defense mechanism against recurrent vulvovaginal candidiasis is not well understood, in part because of the lack of a well-defined murine model of vaginal candidiasis. The present study was undertaken to determine: (i) whether soluble Candida culture filtrate antigens (CaCF) could be used to induce and detect Candida-specific CMI in mice and (ii) whether these antigens would be useful in detecting systemic CMI in mice given an experimental Candida vaginal infection. To this end, mice were immunized subcutaneously with CaCF in complete Freund's adjuvant, and within 7 days they developed Candida-specific DTH reactivity detected by footpad swelling (increase in footpad thickness, 0.36 mm) 24 h after footpad challenge with CaCF. Adoptive transfer studies showed that the DTH responsiveness was elicited by CD4+ DTH T cells. In mice given a vaginal inoculum of C. albicans blastoconidia (5 x 10(5)), footpad challenge with CaCF resulted in positive DTH responses (0.24 mm) as early as 1 week, responses similar to immunization in 2 to 3 weeks (0.33 mm), and sustained low levels of DTH reactivity (0.15 mm) through 10 weeks of vaginal infection. Vaginal lavage cultures revealed that peak vaginal Candida burden occurred 1 week post-vaginal inoculation (10(5) CFU) and declined 16-fold by week 10. These results provide evidence that Candida-specific systemic CMI is generated and can be detected longitudinally in mice with Candida vaginitis by a multiantigen preparation of Candida organisms which both initiates and detects Candida-specific CMI.     

H-Y antigen expression in patients with X-autosomal translocations and gonadal dysgenesis

Cells from three patients with early gonadal failure and a balanced reciprocal translocation involving the long arm of the X chromosome and an autosome were studied. Fibroblasts from a patient with a similar balanced reciprocal translocation but normal reproductive capabilities were also studied. Two of the four patients were found to have serologically detectable H-Y antigen on their cells. Since H-Y antigen has been found on the cells of other patients with X chromosome abnormalities but without a Y chromosome, it is thought that the X chromosome plays a role in the regulation of H-Y antigen expression. This study suggests that the long arm of the X chromosome may be involved but the location of a regulatory gene cannot be identified in these studies. These cases do not permit us to implicate H-Y antigen as a cause of gonadal dysgenesis and early gonadal failure in females who have structurally abnormal X chromosomes.     

Do Treatment Plans Matter? Moving From Recommendations to Action

We investigated whether a service-planning document outlining recommendations for what providers should address in treatment (i.e., targets) and the associated clinical techniques they should employ (i.e., practices) influenced the targets and practices that providers reported actually implementing during the subsequent treatment episode. Participants included 94 youths ages 4 to 17 (M = 13.57, SD = 3.59) who received community-based mental health services from the Hawai'i Child and Adolescent Mental Health Division. Data on targets and practices were compared across initial Mental Health Treatment Plans and Monthly Treatment and Progress Summaries. Data were analyzed using two-level, generalized mixed effects models with two-way cross-classification or linear mixed effects models. Providers were more likely to report the use of targets and practices in treatment if they were included within the treatment plan. In addition, the more closely targets addressed during treatment followed the recommended targets from the treatment plan, the more closely implemented practices followed the recommended practices listed in the treatment plan. Furthermore, as providers shifted their focus to different targets, a shift in their use of practices was also evident over time. Last, practices for which there is demonstrated efficacy for particular targets were more likely to be used. Service planning documents appear to help organize care; however, results also suggest possible limitations to the current system. These findings highlight potential areas for improvement in planning and care delivery.     

Effect of smoking cessation on serum apolipoprotein A-I and A-II concentrations.

This study investigated the effects of 6 weeks' smoking cessation on serum levels of total-cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C) and apolipoproteins A-I and A-II (apo A-I and apo A-II) in 64 subjects of both sexes. Smoking cessation was associated with an increase in levels of apo A-II. Concurrent changes in weight and alcohol consumption during attempted smoking cessation, together with change in thiocyanate level, were entered as predictor variables into a multiple regression analysis. The change in apo A-II was found to be best accounted for by change in plasma thiocyanate level, and, in women, change in HDL-C and apo A-I by change in weight. The changes induced by smoking cessation may be due, at least in part, to associated changes in alcohol consumption and/or dietary intake, but in the case of apo A-II there is evidence of a more direct effect.     

Regulation of intracellular Ca concentration by interleukin-1β in rat cortical synaptosomes: an age-related study

The pro-inflammatory cytokine interleukin-1β (IL-1β) is released by cells during injury and stress, and increased neuronal expression of IL-1β is a feature of age-related neurodegeneration. We have recently reported that IL-1β has a biphasic effect on the K⁺-induced rise in intracellular Ca²⁺ concentration ([Ca²⁺]_i) in cortical synaptosomes, exerting an inhibitory effect on the K⁺-induced rise in [Ca²⁺]_i at lower (3.5 ng/mL) concentrations and a stimulatory effect on the K⁺-induced rise in [Ca²⁺]_i at higher (100 ng/mL) concentrations. In the present study, we observed that the K⁺-induced rise in [Ca²⁺]_i was inhibited to a similar extent by the lower concentration of IL-1β in cortical synaptosomes prepared from young (3-month-old), middle-aged (12-month-old) and aged (24-month-old) rats. In contrast, cortical synaptosomes prepared from the aged rats exhibited an increased susceptibility to the higher concentration of IL-1β, resulting in a marked elevation in [Ca²⁺]_i. We propose that the age-related increase in neuronal concentration of IL-1β promotes a dramatic elevation in [Ca²⁺]_i following membrane depolarization, thereby altering Ca²⁺ homeostasis and exacerbating neuronal vulnerability to excitotoxicity.     

Apolipoprotein A-I and A-II levels in an Australian population

Values for apolipoproteins A-I and A-II (apo A-I and apo A-II) are reported for 389 women and 390 men in the town of Busselton, Western Australia. Apo A-I levels were found to be relatively constant with age in men but to rise with age in women. Apo A-II levels remained constant with age in men until older age, when they declined, but rose with age in women, showing a fall in the oldest age group. Apo A-I levels were greater in women than in men, but apo A-II levels were lower in younger women than in younger men, and higher in older women than in older men. On stepwise multiple regression analysis, neither apo A-I nor apo A-II levels showed an independent relationship with age in women; the same was true for apo A-I in men. Alcohol consumption was directly associated with apo A-I and A-II levels in both sexes; adiposity was inversely associated with apo A-I levels in both sexes but with apo A-II only in women. Triglyceride levels showed an inverse association with apo A-II in women. Frequency of exercise was independently and directly associated with apo A-I and A-II levels in women only.     

Who supports the support workers? Cross-sectional survey of support workers' experience and views

Support groups provide information and emotional support to families. Despite a recent growth in the number and size of these groups, there are no formal structures in place to provide support for the support worker. We performed a cross-sectional survey using a self-completion postal questionnaire, with the aim of identifying the structure, training needs and support given to workers. The participants were support workers from 112 United Kingdom-based organisations listed on the 'Contact a Family' website (www.cafamily.co.uk). We received 104 replies from 50/112 organisations (44%). Of these, 94/104 (90%) worked from home as volunteers. Two-thirds, 69/104, admitted times when they struggled to cope. A total of 43 (41%) admitted occasions of concern over the care given by a client to their affected relative. No group employed a professional to act in a clinical supervisory role. Our study suggests that support workers are highly committed to their role; these workers need support to ensure that they give appropriate advice under difficult circumstances.