The radial depth-dose distribution of a 188W/188Re beta line source measured with novel,ultra-thin TLDs in a PMMA phantom: comparison with Monte Carlo simulations

The radial depth-dose distribution of a prototype 188W/188Re beta particle line source of known activity has been measured in a PMMA phantom, using a novel, ultra-thin type of LiF:Mg,Cu,P thermoluminescent detector (TLD). The measured radial dose function of this intravascular brachytherapy source agrees well with MCNP4C Monte Carlo simulations, which indicate that 188Re accounts for > or = 99% of the dose between 1 mm and 5 mm radial distance from the source axis. The TLDs were calibrated using a 90Sr/90Y beta secondary standard. Several correction factors are calculated using analytical and Monte Carlo methods. An analysis of the measurement uncertainty is made. Since it is partly determined by components of uncertainty arising from random effects, repeated measurements yield a lower uncertainty. The expanded uncertainty in the absolute dose at 2 mm radial distance equals 11%, 10%, 9% and 8% for 1, 2, 3 and 5 measurements, respectively. After a correction for source non-uniformity, the measured dose rate per unit source activity at 2 mm radial distance equals (1.53 +/- 0.16) Gy min(-1) GBq(-1) (2sigma), in agreement with the value of (1.45 +/- 0.01) Gy min(-1) GBq(-1) (2sigma) predicted by the MCNP4C simulations.     

Ellis‐van Creveld syndrome in a patient from Tanzania

We report an African infant with Ellis‐van Creveld (EVC) syndrome. EVC syndrome is a chondral and ectodermal dysplasia with autosomal recessive transmission. The baby presented with polydactyly, short limbs and atrioventricular septal defect, but was withdrawn from clinical follow up for the first year of life. Initial hematological abnormalities could not be explained and normalized later. EVC syndrome was confirmed by genetic analysis that showed two pathogenic mutations in the EVC2 gene, c.653_654del, p.Val218Glyfs*12 in exon 5, and c.2710C>T, p.Gln904* in exon 16. The variant c.653_654del; p.Val218Glyfs*12 in exon 5 has not been described before. Our review of medical literature suggested this is the first molecularly confirmed case of EVC syndrome in sub‐Saharan Africa.     

Alagille syndrome: family studies.

Alagille syndrome (AGS) is one of the major forms of chronic liver disease in childhood with severe morbidity and a mortality of 10 to 20%. It is characterised by cholestasis of variable severity with paucity of interlobular bile ducts and anomalies of the cardiovascular system, skeleton, eyes, and face. Previous studies suggest a wide variation in the expression of the disease and a high incidence of new mutations. To determine more accurately the rate of new mutations and to develop criteria for detecting the disorder in parents we systematically investigated parents in 14 families with an affected child. Clinical examination was supplemented by liver function tests, echocardiography, radiographic examination of the spine and forearm, ophthalmological assessment, and chromosome analysis. Six parents had typical anomalies in two or more systems pointing to the presence of autosomal dominant inheritance. Systematic screening of parents for the features defined in this study should improve the accuracy of genetic counselling.     

Interinstitutional variations of sensitometric curves of radiographic dosimetric films

Depth and field size dependence of the sensitometric curves of radiographic films have been studied by various groups. Limited information is, however, available on the magnitude of the variations in sensitometric curves applied in clinical practice in different institutions. In this study we assessed in a systematic way the effect of the various parameters influencing the shape of the sensitometric curve: batch composition, irradiation conditions, film processing, and film scanning. Two types of film, Kodak X-Omat V and CEA TVS, were irradiated, processed, and analyzed in three different institutions. The interinstitutional variation of the sensitometric curves, expressed as the OD variation at 50 cGy, can be up to 32% and is mainly caused by differences in film processing and to a lesser degree to differences in batch composition, film scanning, and irradiation conditions. For the Kodak films, the average OD difference at 50 cGy between the three institutions is 17% as a result of differences in batch composition and 25% due to differences in processing conditions. For the CEA films these data are 6% and 24%, respectively. The long-term variation of the sensitometric curves of KODAK films in one institution was smaller than the differences in batch composition between the three institutions. The sensitometric curves of CEA films showed in one institution a large variation with time; the shape gradually varied from sigmoidal to quasilinear. By using relative OD values rather than absolute OD values, variations in sensitometric curves of KODAK films can be reduced to 2%. Consequently, one sensitometric curve is sufficient to derive relative dose values. If processing conditions are well controlled, it might therefore be advantageous to determine the absolute OD only at one or two dose values, in combination with a "universal" relative sensitometric curve.     

Segmented filamentous bacteria are potent stimuli of a physiologically normal state of the murine gut mucosal immune system

Segmented filamentous bacteria (SFB) are autochthonous bacteria inhabiting the intestinal tracts of many species, including humans. We studied the effect of SFB on the mucosal immune system by monoassociating formerly germfree C3H/HeN mice with SFB. At various time points during 190 days of colonization, fragment cultures of small intestine and Peyer's patches (PP) were analyzed for total immunoglobulin A (IgA) and SFB-specific IgA production. Also, phenotypic changes indicating germinal center reactions (GCRs) and the activation of CD4(+) T cells in PP were determined by using fluorescence-activated cell sorter analyses. A second group of SFB-monoassociated mice was colonized with a gram-negative commensal, Morganella morganii, to determine if the mucosal immune system was again stimulated and to evaluate the effect of prior colonization with SFB on the ability of M. morganii to translocate to the spleen and mesenteric lymph nodes. We found that SFB stimulated GCRs in PP from day 6 after monoassociation, that GCRs only gradually waned over the entire length of colonization, that natural IgA production was increased to levels 24 to 63% of that of conventionally reared mice, and that SFB-specific IgA was produced but accounted for less than 1.4% of total IgA. Also, the proportion of CD4(+), CD45RBlow T cells, indicative of activated cells, gradually increased in the PP to the level found in conventionally reared mice. Secondary colonization with M. morganii was able to stimulate GCRs anew, leading to a specific IgA antibody response. Previous stimulation of mucosal immunity by SFB did not prevent the translocation of M. morganii in the double-colonized mice. Our findings generally indicate that SFB are one of the single most potent microbial stimuli of the gut mucosal immune system.     

Interepithelial cells of the oral mucosa in mice

Summary Non-epithelial mesenchymal and neuroectodermal cells occur between the keratinocytes in the stratified squamous epithelium of the oral mucosa. These cells cannot be classified adequately by light microscopy. In the present study the oral mucosa of the lip, cheek and tongue of 50 mice were studied by light and electron microscopy. 3,025 mononuclear interepithelial cells were documented and analysed.Monocytogenic macrophages, plasma cells and mast cells were not found interepithelially and cannot be regarded as a regular constituent of the epithelium. Only a few neuroectodermal cells — in mice these are exclusively Merkel cells, with no melanocytes — were localized in the epithelium. The majority of the interepithelial cell population is made up of lymphocytes (22.8%) and Langerhans cells (56.8%). They are an integral constituent of the epithelium. Lymphocytes with rounded and indented nuclei can be identified. The larger and dendritic Langerhans cells are a specific cell of squamous epithelium and also occur in the oral mucosa. Not all cells which feature the cytological characteristics of Langerhans cells contain Langerhans or Birbeck granules. Accordingly these granules cannot be considered an exclusive identification characteristic. Two types of Langerhans cells can be differentiated. 80.9% have the more or less typical appearance known from the epidermis and were termed macrophagocytoid Langerhans cells. The nuclei are irregularly indented and moderately heterochromatic. 19.1% possessed conspicuous large, spherical, euchromatic nuclei and an electron-lucent cytoplasm. These were termed reticuloid Langerhans cells. About 20% of the interepithelial cell population could not be identified, neither as typical lymphocytes nor as Langerhans cells. These were small to medium sized cells with deeply indented cerebriform strongly heterochromatic nuclei. They are similar to the Sézary cells or mycosis fungoides cells of epidermotropic human T-cell lymphomas. The lymphocytic nature of these cells has been confirmed. It seems likely that differentiation of lymphocytes to cerebriform cells occurs within the epithelium. It is further discussed whether cerebriform cells are precursors of Langerhans cells, a conclusion suggested morphologically by transitional forms. This would imply that Langerhans cells originate from lymphocytes, and that the cerebriform cell is an intermediate step of differentiation. The microenvironment of the squamous epithelium may play a role in the process of differentiation, which could explain the epitheliotropy of lymphocytes. The possibility is considered that Langerhans cells and interdigitating reticulum cells of the T-cell area of lymph nodes are identical. The close functional cooperation of Langerhans cells, lymphocytes, and interdigitating reticulum cells in immunological defenses against external antigens is discussed.The authors wish to express their sincere appreciation to Miss P. Starck and Miss I. Brandt for invaluable technical assistance in this project.     

Planned lesbian families: their desire and motivation to have children

BACKGROUND: There is no information about the desire and motivation for children among planned lesbian families. The overall aim of this research was to examine whether planned lesbian families differ from heterosexual families in desire and motivation to have a child. The reason for studying this is that desire and motivation to have children are characteristics that are supposed to effect parenting and the parent-child relationship. METHODS: A total of 100 lesbian two-mother families were compared with 100 heterosexual families. All data were collected by means of questionnaires. RESULTS: Lesbian parents and heterosexual parents rank their parenthood quite similarly; however, happiness is significantly more important for lesbian mothers than it is for heterosexual parents and identity development is less important for lesbian mothers than it is for heterosexual parents. Furthermore, compared with heterosexual parents, lesbian parents had spent more time thinking about their motives for having children, and their desire to have a child was stronger. CONCLUSIONS: Lesbian parents especially differ from heterosexual parents in that their desire to have a child is much stronger. The study's findings may be helpful for counsellors in their work to inform and assist lesbian couples in their decision to have a child.     

SHIP represses mast cell activation and reveals that IgE alone triggers signaling pathways which enhance normal mast cell survival

The hemopoietic specific, Src homology 2-containing inositol 5' phosphatase (SHIP) hydrolyzes the phosphatidylinositol (PI)-3-kinase generated second messenger, PI-3,4,5-trisphosphate (PIP(3)), to PI-3,4-bisphosphate (PI-3,4-P(2)) in normal bone marrow derived mast cells (BMMCs). As a consequence, SHIP negatively regulates IgE+antigen (Ag)-induced degranulation as well as leukotriene and inflammatory cytokine production. Interestingly, in the absence of SHIP, BMMCs degranulate extensively with IgE alone, i.e. without Ag, suggesting that IgE alone is capable of stimulating signaling in normal BMMCs and that SHIP prevents this signaling from progressing to degranulation. To test this, we compared signaling events triggered by monomeric IgE versus IgE+Ag in normal BMMCs and found that multiple pathways are triggered by monomeric IgE alone and, while they are in general weaker than those stimulated by IgE+Ag, they are more prolonged. Moreover, while SHIP prevents this IgE-induced signalling from progressing to degranulation or leukotriene production it allows sufficient production of autocrine acting cytokines, in part by activation of NFkappaB, to enhance BMMC survival. Interestingly, the activation of NFkappaB and the level of cytokines produced are far higher with IgE than with IgE+Ag. Moreover, IgE alone maintains Bcl-X(L) levels and enhances the adhesion of BMMCs to fibronectin and this likely enhances their survival still further.