A Lagrangian model of the evolution of the particulate size distribution of vehicular emissions.

The emission inventory for London indicates that nearly 80% of the particulate emissions derive from vehicular sources. Most of this mass is in the form of ultrafine submicrometer particles which are of concern because of their influence on lung function. The prediction of their dispersion in the atmosphere coupled to the physical and chemical transformations which affect their size distribution and concentration are of great importance. This paper reports the first results from a new meso-scale Lagrangian model which follows the particulate emissions and the evolution of their size distribution across the city. The vehicular emissions are based on the published inventory, corrected to time of day, while other emissions are assumed steady. The initial size distributions of background and emitted particles are represented by the sum of three lognormal distributions. Meteorological data are derived from Meteorological Office reports and are preprocessed to obtain the hourly values of boundary layer depth, Monin-Obukov (MO) length, friction velocity, etc., needed for the computation of the vertical dispersion process via eddy diffusivities and the aerodynamic component of the dry deposition process. In the vertical direction, three layers are assumed-surface layer (typically 50 m), canopy layer and one further layer up to the prevailing boundary layer depth. Currently, the model includes wet and dry deposition and coagulation but not chemical reaction, nucleation or deliquescence. Trajectories are evolved for several hours across the city and the number size distributions and mass concentrations (PM10, PM2.5, PM1 and PM0.1) output at each step. This enables the vehicular contributions over and above the background concentration in each size range to be studied in detail. Data from the model have been compared with experimental data for one of the London background sites where particle number size distribution up to 450 nm (SMPS), plus PM10 and PM2.5 (TEOM) data are available.

The thymus in the mouse changes its activity during pregnancy: a study of the microenvironment.

The mouse thymus changes dramatically during pregnancy. It shrinks in size, and the cortex is extensively reduced from midpregnancy onwards. Despite this, there is surprisingly little evidence for any increase in apoptosis, and considerable evidence that mitosis of thymocytes continues throughout pregnancy. In spite of overall involution the thymic medulla actually expands in midpregnancy due to a combination of mitosis of epithelial cells and an accumulation of lymphocytes. The extent and nature of these changes are examined in this study at the ultrastructural level. The epithelial cells of the subcapsular cortex (type 1 cells) become wrinkled and exhibit powers of phagocytosis, whilst the other cortical epithelial cells are relatively unchanged, although the formation of epithelial/thymocyte rosettes and thymic nurse cells is more clearly seen in midpregnancy than usual. Other changes associated with pregnancy involve the medullary epithelial cells that undergo an increased level of mitosis. Their greater numbers surround accumulations of lymphocytes to form the characteristic medullary epithelial rings. Cell movement through blood vessel walls was clearly observed in midpregnancy, but not at other times. Interdigitating cells in the medulla become more conspicuous as pregnancy proceeds and the cells become phagocytic. The endoplasmic reticulum in plasma cells becomes expanded, indicating increased secretory activity. These results highlight the active nature of the thymus in pregnancy in spite of its involution. This picture contradicts the conventional notion that an involuted thymus is inactive.

Immunoreactivity of neural crest-derived cells in thymic tissue developing under the rat kidney capsule.

In order to study the functional development of a thymus in an experimental model, small pieces of adult rat thymic tissue were cultured for 9 days and implanted under the kidney capsule of littermates. The tissues were examined with a panel of antibodies raised against thymic and neural factors and neural crest cells at intervals from 5 to 13 days. At 5 days post-implantation, there were groups of L1+ cells within the implants that reacted with antibodies raised against neural and neural crest cell markers. L1+ cells were highly mitotic, rounded cells measuring 8.7 +/- 0.6 micrometer in diameter. Double immunostaining with different combinations of antibodies showed that 94% of the L1+ cells were also TH+, and many were HNK-1/NCAM+, PGP 9.5+, NGF+, chromogranin A+, VIP+, S100+, CGRP+, GAD+, and A2B5+. A few were also pan-cytokeratin+. These results indicate that these cells are derived from neural crest derived cells and belong to the neuroepithelial line of development. The L1+ cells were most numerous before nerves appeared (about Day 9) and reduced in number and extent as the thymus differentiated. The neural crest cells occasionally had long cytoplasmic extensions, but it was not possible to decide if they formed the nerves that appeared in the implants. Adult thymuses also contained a population of L1+ and HNK-1/NCAM+ cells, mainly in the subcapsular cortex, the septa, and the medulla. These cells could be a source of neural crest cells able to repopulate the implant. The adult thymus may always contain a reservoir of cells potentially capable of producing neuropeptides and transmitter factors required for thymic growth and regeneration.

The noradrenergic innervation of the rat thymus during pregnancy and in the post partum period.

The noradrenergic innervation of the rat thymus during pregnancy and the post partum period was examined by a sucrose glyoxylic acid method for catecholamines, and by high pressure liquid chromatography. Fluorescent nerves decreased in number throughout pregnancy when there was an overall loss in thymic weight due to cortical involution. These changes are maximal by parturition. There was a dramatic increase in nerves between d 21 of pregnancy and d 1 after parturition, especially in the capsule and around blood vessels in the connective tissue septa. The neonates were removed at parturition and thymic weight was rapidly regained. The increased numbers of nerves remained throughout this post partum period. Noradrenaline levels in the thymus altered in a similar pattern throughout pregnancy and the post partum period, but did not parallel thymic weight changes. The mean noradrenaline concentration in the virgin thymus was 1063 +/- 107 pg/mg protein. Levels remained similar during early pregnancy and increased significantly at d 16. Virgin levels were regained by d 21. Values peaked after parturition but rapidly decreased over the next 3 days, and remained at or below virgin levels to d 28 except for a transient rise at d 10 post partum. Adrenaline values were consistently below detection levels. This study shows that there are variations in both nerves visualised, and in neurotransmitter (noradrenaline) content in the thymus during the course of pregnancy and the post partum period. Thus thymic function could be influenced by central events (levels of catecholamines in peripheral blood) as well as local events mediated by transmitter changes in nerves.

The thymus in pregnancy: the interplay of neural, endocrine and immune influences.

This article discusses the dramatic events that accompany thymic involution during pregnancy, and traces the possible immune, neural and endocrine interactions that may occur. Ann Clarke and Marion Kendall present accumulating evidence that activity, not inactivity, is a feature of the thymus at this time. Whilst the cortex shrinks, the medulla enlarges and rearranges to create a microenvironment containing increased numbers of mature thymocytes. It is suggested that these recently derived T cells may contribute to the unique populations of cells with suppressive function that appear during pregnancy, and thereby contribute to the immune suppression of the mother to paternal and fetal antigens. In addition, the pregnancy-associated cortical involution of the thymus may reflect the deletion of clones with potential reactivity to paternal and/or fetal antigens.

The effects of pregnancy on the mouse thymic epithelium.

Changes in the murine thymus during pregnancy were studied using immunocytochemistry with monoclonal antibodies against thymic epithelial, neuroendocrine, and thymulin-producing cells, fibroblasts, blood vessels and connective tissue components. Extensive alterations occur in mid-pregnancy. The medulla was greatly enlarged in the involuted thymus, and there were greater numbers of epithelial cells. These epithelial cells had an altered distribution forming large structures surrounding spherical masses of mononuclear cells, lacked epithelial cells and often contained a central blood vessel with fibroblasts and connective tissue. We have called these structures 'medullary epithelial rings' (MERs). To our knowledge these structures have not been described before. Late in pregnancy the loss of the central mononuclear cells leaves collapsed structures in a smaller medulla that nevertheless retains many epithelial cells. In virgins and early-pregnancy, there are cortical channels free of epithelial cells that are very infrequent later in pregnancy. This may reflect the loss of steroid-sensitive thymocytes from the cortex. The influence of sex-steroids, neurological impulses and immune activity in causing the changes are discussed, as are the possible consequences in pregnancy of a reduced, thymocyte-depleted cortex and an enlarged medulla that shows great complexity and activity.

Histological changes in the thymus during mouse pregnancy.

We studied the cells and microenvironments of the thymus in the pregnant mouse. A morphological and histological study at the light and electron microscope levels shows that the thymus continues to remain active despite massive loss of cortical cells. Many changes are seen in the cortex, but the medulla is relatively unaltered. In very early pregnancy a reduction in cell death and an increase in the numbers of blast cells and mitotic figures indicate a greater activity than in virgin animals. Later in pregnancy, when two-thirds of the cortical cells are lost, there is a continuing presence of mitotic figures and blast cells. Death of thymocytes by apoptosis occurs in associations (rosettes) with macrophages or cortical epithelial cells in the subcapsular and outer cortex. Death of thymocytes with adjacent epithelial cells also occurs in the deep cortex, as it does in virgin females. These results suggest that involution in pregnancy is structurally different from that induced by acute hydrocortisone treatment or other drugs. This supports the view that the term thymic involution describes not one distinct process, but several different processes. The relevance of these findings to the deletion of thymocytes reactive to paternal and fetal antigen is discussed.

Levels of circulating immune complexes in patients with ovarian cancer.

Sera from patients with ovarian tumours were assayed for circulating immune complexes (CIC) by four well established assays based on the interaction of immune complexes with components of the complement system. There was no difference in control, pre- or post-operative or BCG-treated patients' sera. Levels were also unchanged in sera in antigen excess. In patients with ovarian tumours therefore the measurement of CIC would appear to be of little value as a screening test, as a guide to the extent of disease, prognosis or therapy. In a small pilot therapy-trial there was no difference in the survival rate between patients with stage III and IV ovarian cancer treated with cyclophosphamide plus BCG and those who received only cyclophosphamide. Treatment with BCG was associated with postoperative pyrexia and a prolonged hospital stay.

Use of modified subcutaneous right-atrial catheter for venous access in leukaemic patients.

A large-diameter indwelling subcutaneous right-atrial catheter was inserted in 25 patients with haematological malignancies and neutropenia to provide ready access to the venous system for all infusions and blood aspirations. The median duration of catheter placement was 70 days. In 23 patients (92%) the catheter was used successfully until remission or death. Catheter-related exit-site infectons, generally mild, occurred in 14 patients (56%), Staphylococcus epidermidis being the predominant organism cultured. Septicaemia occurred in 11 neutropenic patients (44%). In 2 patients the same organism was grown from blood and exit site. The use of this catheter greatly facilitates patient care and support, minimises discomfort, and is associated with an acceptable rate of complications.

C1q-binding activity of serum from allogeneically and syngeneically pregnant mice.

C1q-binding activity of serum during allogeneic and syngeneic pregnancy in mice was measured using the direct [125I]C1q-binding assay. In both strains there was an initial tendency for levels to rise in very early pregnancy (Days 2 and 4) followed by a progressive fall in C1q binding to a level significantly lower than that found in non-pregnant animals. The changes were present in both syngeneic and allogeneic pregnancies but the later changes were more pronounced in the latter. The presence of changes associated with syngeneic pregnancy suggests that these profiles are at least in part independent of genetic differences between mother and embryo.

Measurement of thymus weight, lumbar node weight and progesterone levels in syngeneically pregnant, allogeneically pregnant, and pseudopregnant mice.

Female CBA mice were mated to fertile CBA males, to vasectomized CBA males, to fertile C57BL males or to vasectomized C57BL males. After allogeneic or syngeneic mating the extent of thymic involution on the 10th day of pregnancy and pseudopregnancy was similar. Lumbar lymph node weight was not affected by pseudopregnancy but increased similarly in allogeneic and syngeneic pregnancies. Serum progesterone levels on the 10th day of pseudopregnancy were similar to those of non-pregnant females, and significantly lower than those of pregnant females. On the 4th to 7th days progesterone levels in pseudopregnant animals were equal to those in pregnant animals. Progesterone levels and thymic involution were similar in syngeneically and allogeneically pregnant females. Progesterone levels were negatively correlated with thymus weight but reached significance only when the mating was allogeneic. It is suggested that there is an interaction between progesterone concentrations and the degree of thymic involution during pregnancy.

Pregnancy-induced involution of the thymus can be prevented by immunizing with paternal skin grafts: a strain-dependent effect.

C57Bl female mice immunized and then mated to CBA males do not show the normal pregnancy-dependent involution of the thymus. In the reciprocal mating combination thymic involution is normal.

Cenetic and immunological aspects of litter size in the mouse.

The effects of antigenic differences between mother and fetus on implantation number and on post-implantation mortality were studied. No evidence was found to support the hypothesis that these two measurements were affected by such antigenic differences or by prior immunization of the mother to paternal antigens.

Chronic haemodialysis using saphenous vein fistulae.

Since 1969 four leg fistulae and 14 arm fistulae using the saphenous vein have been constructed in chronic haemodialysis patients. The operative procedures are described and the results show that these fistulae are an excellent alternative when the construction of Cimino-Brescia fistulae becomes impossible. Of the 14 arm fistulae, nine are still patent and in use, three have thrombosed and two patients have died of unrelated causes with the fistulae intact.