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The development and operation of Liquid Argon Time Projection Chambers (LAr TPCs) for neutrino physics has created a need for new approaches to pattern recognition, in order to fully exploit the superb imaging capabilities offered by this technology. The Pandora Software Development Kit provides functionality to aid the process of designing, implementing and running pattern recognition algorithms. It promotes the use of a multi-algorithm approach to pattern recognition: individual algorithms each address a specific task in a particular topology; a series of many tens of algorithms then carefully builds-up a picture of the event. The input to the Pandora pattern recognition is a list of 2D Hits. The output from the chain of over 70 algorithms is a hierarchy of reconstructed 3D Particles, each with an identified particle type, vertex and direction.

Background The aetiology and exact incidence of infantile haemangiomas (IHs) are unknown. Prior studies have noted immunohistochemical and biological characteristics shared by IHs and placental tissue. Objectives We investigated the possible association between placental anomalies and the development of IHs, as well as the demographic characteristics and other risk factors for IHs. Patients and methods Pregnant women (n = 578) were prospectively enrolled and their offspring followed for 9 months. Placental evaluations were performed and demographic data collected on all mother-infant pairs. Results We evaluated 594 infants: 34 haemangiomas [either IH or congenital (CH)] were identified in 29 infants, yielding an incidence of 4·5% for IH (27 infants) and 0·3% for CH (two infants). Placental anomalies were noted in almost 35% of haemangioma-related pregnancies, approximately twice the incidence noted in pregnancies with unaffected infants (P = 0·025). Other risk factors for IH included prematurity (P = 0·016) and low birth weight (P = 0·028). All IHs were present by 3 months of age, and cessation of growth had occurred in all by 9 months of age. Most occurred on the trunk. Of note, 20% of identified IHs were abortive or telangiectatic in nature, small focal lesions that did not proliferate beyond 3 months of age. Only one IH required intervention. Conclusions This is the first prospective American study to document the incidence of IHs in infants followed from birth to early infancy. The association with placental anomalies was statistically significant. The overall incidence mirrors prior estimates, but the need for treatment was lower than previously reported.

A numerical study was performed of particle capture in the entrance region of a crack, with computational domain consisting of the crack channel and inlet and exit reservoirs that are much larger than the channel width. The simulations examined different mechanisms for particle capture within the channel entrance region, including collision on the inlet reservoir wall just outside the crack channel, collision within the crack channel due to cross-stream inertia imparted by the entrance flow, collision induced by Brownian diffusion both on the inlet reservoir wall outside of the channel and within the channel, and gravitational collision within the channel. A detailed study of the variation of the entrance penetration factor with parameters such as the Stokes, Peclet, and Froude numbers was performed, and comparison of the numerical predictions with different theoretical expressions was made when the latter were available. Validity of the assumption of penetration factor independence was also examined for cases where both entrance region inertia and gravitational settling are significant.Copyright 2015 American Association for Aerosol Research

To initiate studies on the regulation of tu- bulin expression and microtubule organization in the phytopathogenic Oomycete, Phytophthora cinna- momi, a gene encoding 3-tubulin was cloned and se- quenced. The gene has no introns and encodes a protein of 445 amino acids. Genomic Southern blots indicate a single copy of the 3-tubulin gene in the P cinnamomi genome. Comparison of the P cinnamomi B3-tubulin gene sequence with B3-tubulin genes from a range of fungi, algae and protists supports the hy- pothesis that the Oomycetes are more closely related to the algae and protists than they are to the higher fungi.

The activation of rodent and human mast cells can occur through the cross-linking of tetrameric IgE receptors each containing single alpha- and beta- and two gamma-subunits. However, the factors that regulate the in vivo expression of Fc epsilonRI are poorly understood. We have examined the expression of the Fc epsilonRI beta-subunit in the Nippostrongylus brasiliensis (Nb)-induced mode l of rat intestinal inflammation. We developed a double-staining technique for mast cell granules (Alcian blue) and the beta-subunit of Fc epsilonRI. The intensity of immunohistochemical staining per mast cell was quantified using an image analysis system. Jejunal and tongue mast cells of Lewis rats were visible by Alcian blue staining before Nb infection, but they expressed very low levels of beta-subunit as assessed by immunohistochemical staining. These levels were increased by day 11 postinfection and reached a maximum at day 14. Since serum IgE levels correlated well with the degree of beta-subunit expression, we investigated whether the observed enhancement of receptor expression might occur through the stabilization of receptor complexes by IgE. Therefore, Lewis rats were treated with myeloma IgE, and beta-subunit expression was examined. In both tongue and jejunal tissue, a significant rise in beta-subunit expression was observed in response to IgE injection, although levels of beta-subunit expression were not as high as those observed in Nb-infected animals. The increase in beta-subunit expression was accompanied by an increase in the amount of mast cell-associated IgE. These observations may have important implications for the regulation of IgE receptor expression during disease.

Regulatory B (Breg) cells are known to modulate immune responses through predominantly interleukin-10 (IL-10)-dependent mechanisms and can be hypothetically divided into innate and adaptive subsets based on the nature of their activating signals. However, the specific role of different Breg subsets in modulating immune responses remains ambiguous. Here we have shown that Chlamydia induces IL-10-producing splenic B-cell populations consisting of CD43(+) and CD43(-) subsets of IgM(hi)IgD(lo) innate-like B (ILB) cells in vitro. While CD43(+)IL-10-producing B cells displayed innate type features and were readily induced by Chlamydia via Toll-like-receptor (TLR) signaling, CD43(-)IL-10-producing B cells required additional B-cell activating factor (BAFF)-mediated signals from dendritic cells (DCs) for their differentiation and activation, thereby classifying them as adaptive type Bregs. Importantly, CD43(-), but not CD43(+), IL-10-producing ILB cells displayed bona fide Breg activity by potently suppressing interferon-γ (IFN-γ) production in vitro in an IL-10-dependent manner. Furthermore, a novel CD43(-)CD1d(hi)CD5(+) IL-10-producing Breg population was predominantly induced by Chlamydia genital infection in vivo. Correspondingly, mixed bone marrow chimeric mice with B-cell-specific IL-10 deficiency exhibited significantly increased type 1 immune responses, decreased bacterial burden, and reduced oviduct pathology upon infection. Our data demonstrate for the first time a distinct role for CD43(-)CD1d(hi)CD5(+)-adaptive Bregs over CD43(+) innate counterparts in controlling mucosal responses against intracellular bacterial infection.

Mast cells have been traditionally associated with an acute allergic response. However, their role in regulating chronic inflammatory processes must also be considered in view of evidence that mast cells synthesize and release a number of cytokines. In this study, we have examined the effect of cholera toxin (CT) on peritoneal mast cell IL-6 and TNF-alpha production. Highly purified, freshly isolated, rat peritoneal mast cells from Brown Norway rats were cultured in the presence of CT or its B subunit (CTB) alone or in combination with anti-IgE or bacterial LPS. Histamine release was measured after 10 min; IL-16 and TNF-alpha production was assessed in supernatants after 18 h. We found that CT or CTB alone did not affect histamine release; however, mast cell IL-6 production was significantly enhanced by CT but not by CTB. In contrast, constitutive production of TNF-alpha was inhibited by CT. The effects of CT were similar to our previous observations of the actions of prostaglandin E2 on mast cells. We also examined the effects of CT in combination with other mast cell activating agents. CT had no significant effect on anti-IgE-induced histamine release. An additive effect on IL-6 production was observed in the context of LPS. Forskolin, an agent known to increase intracellular cAMP levels, also induced a significant increase in IL-6 production, whereas TNF-alpha production was decreased. These data have important implications for our understanding of the regulation of mast cell cytokine production and the effects of CT on local cytokine production.

TNF-alpha is a cytokine with a wide spectrum of proinflammatory activities. Nasal polyps (NP), which occur in association with allergic rhinitis and asthma, are characterized by a marked infiltration of activated eosinophils, epithelial damage, and varying degrees of stromal fibrosis. By using Southern blot analysis after a reverse transcription-PCR, we detected a signal specific for TNF-alpha mRNA in five of seven NP samples, but not in control nasal mucosal samples. With in situ hybridization, we detected cells expressing mRNA specific for TNF-alpha in eight of thirteen NP samples, but not in four control samples. Counterstaining with chromotrope 2R demonstrated that virtually all cells expressing TNF-alpha message were eosinophils. The ratio of eosinophils expressing TNF-alpha to the total number of eosinophils varied greatly among tissues; as an average, we observed 24% TNF-alpha-positive eosinophils. Using a mAb against human TNF-alpha, we demonstrated TNF-alpha localization in 12 NP tissues (48.8 +/- 16.5 positive cells/mm2) but not in three control samples. Morphologically, cells localizing TNF-alpha were both mononucleated and polynucleated with only a small number of eosinophils, as determined by aniline blue counterstaining. Studies of purified blood eosinophils from a patient with hypereosinophilic syndrome and from four healthy donors indicated that TNF-alpha is produced, but rapidly secreted, so that TNF-alpha mRNA-positive cells contain little detectable protein. Furthermore, cells that retain detectable TNF-alpha may not contain sufficient TNF-alpha mRNA to be detected by using the probe developed for our studies. Together, these findings identify a novel mechanism by which eosinophils may contribute to mucosal inflammation and provide an approach to future investigation.

A computerised ward monitoring system based on Archimedes PC's at each bedside is under development for the PICU at Killingbeck Hospital in Leeds. This work was initiated with a view to reducing the amount of paperwork in the unit. The present paper charts have been broken down into sections for the purpose of entry into the computer. The completed charts may be viewed in tabular form. There are several alternative displays. The default display mode illustrates the patients principal cardiovascular variables over the previous six hours. Alternative graphical displays include 12 hour trend curves for the cardiovascular variables, a screen with one hour trend graphs and panels illustrating the latest values of other patient variables, and graphical 12 hour reviews for clear fluid balance, blood volume balance and respiratory variables. The program also serves as a vehicle for testing an alarm generating system and a cardiovascular status index in the paediatric environment. A separate program has been developed which allows the retrospective construction of data bases by using some or all of the data from one or more of the charts for a series of patients. Finally the difficulties encountered in preliminary trials of the system are discussed. At the present time the program is being run at a central station while attempts are being made to surmount these difficulties.

We report the first detailed comparisons of the rates and spectra of neutral-current neutrino interactions at two widely separated locations. A depletion in the rate at the far site would indicate mixing between muon neutirnos and a sterile particle. No anomalous depletion in the reconstructed energy spectrum is observed. Assuming oscillations occur at a single mass-squared splitting, a fit to the neutral- and charged-current energy spectra limits the fraction of muon neutrino oscillating to a sterile neutrino to be below 0.68 at 90% confidence level. A less stringent limit due to a possible contribution to the measured neutral-current event rate at the far site from electron neutrino appearance at the current experimental limit is also presented., Comment: 5 pages, 3 figures

Toll-like receptors (TLRs) are a family of pattern recognition receptors that are critical for cellular responses to a variety of bacterial, viral, and fungal products. Mast cells are important to host survival in a number of models of bacterial infection and might act as sentinel cells in host defense. We therefore examined the expression of TLRs and associated molecules by murine bone marrow-derived mast cells (BMMCs). BMMCs and the murine mast cell line MC/9 expressed mRNA for TLR2, TLR4, and TLR6 but not TLR5 and for both adapter molecule MD-2 and signaling molecule MyD88 but lacked surface CD14. After activation with the TLR2- and TLR4-dependent stimuli Staphylococcus aureus-derived peptidoglycan and Escherichia coli-derived lipopolysaccharide (LPS), respectively, mast cells produced significant levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha). To determine whether mast cells require TLR4 for cellular responses to LPS, mast cells were derived from the bone marrow cells of C3H/HeJ and C57Bl/10ScNCr mice containing a point mutation and a null mutation, respectively, in TLR4. Using these models, we demonstrated that the BMMC IL-6 and TNF-alpha responses to LPS were completely dependent on functional TLR4 with no significant LPS response observed in its absence. These findings have important implications for the mechanism of mast cell responses to pathogens and their products and suggest that different TLR4-expressing cells might have different thresholds for activation with LPS.

Monophosphoryl lipid A (MPL) is a detoxified derivative of the lipopolysaccharide (LPS) moiety of Salmonella minnesota R595, which has retained immunostimulatory activities. MPL has been administered to many subjects in clinical trials as an adjuvant component of infectious disease vaccines and is currently a component of a licensed cancer vaccine, Melacine (Corixa Inc., Schering Plough). MPL has, in particular, been shown to promote Th1-type antigen specific responses. L-tyrosine is a depot adjuvant which is fully metabolisable and has been successfully employed in allergy vaccines for a number of years.Mice were immunised with MPL adjuvant in conjunction with separate preparations of either ovalbumin or glutaraldehyde-modified ragweed pollen extract both coprecipitated with L-tyrosine. The specific antibody isotypes IgG1, IgG2a, IgG2b and also IgE were measured. Rats received booster injections of keyhole limpet haemocyanin (KLH) in conjunction with MPL adjuvant following priming with KLH in alum alone. KLH-specific antibody responses were measured.It was shown that a combination of L-tyrosine and MPL were synergistic in enhancing murine antigen specific IgG antibody responses without enhancing antigen specific IgE responses. Furthermore, this adjuvant combination promoted strong IgG2 antigen specific responses indicative of a Th1 directed response. In KLH sensitised rats, treatment with MPL was shown to prevent a secondary IgE antibody response when injected with booster injections of antigen.Immunisation of mice with two different antigens adsorbed to L-tyrosine induced a Th1-skewed primary response when in conjunction with MPL adjuvant which also generally enhances a specific IgG response. Incorporation of MPL adjuvant in the immunisation of rats prevented a secondary specific IgE response. These results suggest that the employment of this new adjuvant in clinical allergy vaccination formulations may result in an improved efficacy which could be utilised in various ways to improve compliance.

Pneumonectomy for lung cancer is associated with significant morbidity and mortality. Risk factors for the morbidity and mortality have been reported, but consistent conclusive data are undetermined. Current accepted 30-day mortality rates for pneumonectomy range from 7 to 11 per cent. The objective of this study is to determine whether various perioperative factors can serve as predictors of morbidity and mortality in pneumonectomy patients and to review outcome data on patients undergoing pneumonectomy for lung cancer. A total of 105 patients undergoing pneumonectomy for lung cancer from 1988 through 1998 are studied in a retrospective chart review. The main outcome measure is the 30-day operative mortality and morbidity. Complications occurring in 10 per cent or more of the patients included atrial fibrillation (33.3%), respiratory failure (23.8%), pneumonia (21.9%), and bronchopleural fistula (12.4%). The 30-day mortality rate was 10.5 per cent (11 deaths). By Fisher's exact test for Chi-square only three statistically significant mortality factors were identified: respiratory failure (P0.021), sepsis (P0.008), and male sex (P0.031); respiratory failure, sepsis, and sex were predictors of death. Significant correlation could not be made to predict postoperative morbidity. Overall long-term clinical outcome for pneumonectomy as lung cancer treatment was poor. Clinical judgment remains an essential factor when considering pneumonectomy as an option for lung cancer treatment.

Mast cells are sentinel cells critical to the initiation of innate immune and inflammatory responses, particularly at mucosal surfaces. To fulfill this function they can be activated by several pathogen-associated stimuli to produce cytokines with or without concurrent degranulation. We examined the ability of immunostimulatory DNA sequences including CpG motifs, which are found in increased quantities in bacterial DNA, to activate mouse bone marrow-derived mast cells (mBMMC). Mast cells were treated with a range of doses of CpG-containing oligodeoxynucleotides or control oligodeoxynucleotides without CpG within their sequence. There was a dose-dependent increase in the production of both interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) by mast cells treated with the CpG-containing oligodeoxynucleotides. The cytokine levels induced were directly related to the number of CpG within a given length of sequence. Treatment with oligonucleotides containing 3CpG induced an eightfold increase in TNF production over control incubated mast cells. Other cytokines, including granulocyte-macrophage colony-stimulating factor, IL-4, interferon-gamma, and IL-12 were not induced by oligonucleotide treatment. Neither CpG containing oligodeoxynucleotides nor control oligodeoxynucleotides induced degranulation of mast cells. Bacterial DNA from Escherichia coli also induced IL-6 from mBMMC but neither calf thymus DNA nor methylase-treated E. coli DNA had such an effect. Examination of the uptake of Texas red-labeled CpG and non-CpG-containing oligodeoxynucleotides revealed that they were both similarly taken up by the mBMMC. These results have important implications for the mechanism by which mast cells respond to bacteria and for the potential role of mast cells in DNA vaccination.

Mast cells are known to express high levels of alpha4 integrins including alpha4beta7 and are found in increased numbers in mucosal inflammation. Mast cell accumulation is particularly prominent in the intestine following nematode infection. The adhesion molecule requirements for this process have not yet been defined. The role of alpha4 and beta7 integrin chains in the intestinal mast cell hyperplasia following infection of rats with the nematode parasite Nippostrongylus brasiliensis was examined in this study. Rats were infected with N. brasiliensis larvae and treated with either anti-alpha4 (TA-2), anti-beta7 or isotype-matched control antibodies. The initial mast cell hyperplasia in response to N. brasiliensis infection was significantly inhibited by either anti-alpha4 or anti-beta7 treatment. In contrast, the intestinal eosinophil response to N. brasiliensis infection was not reduced at day 14 or day 16. Elevations in serum IgE levels due to N. brasiliensis infection were also not inhibited by anti-alpha4 or anti-beta7 antibody treatment. Anti-alpha4 antibody but not anti-beta7 antibody treatment also induced a small but significant decrease in the numbers of mast cells in tongue tissue. These data suggest a role for alpha4 integrins, in particular alpha4beta7, in the regulation of mast cell precursor migration to the intestine.

To determine the capacity of pulmonary mast cells (PMC) to degranulate in response to various potential allergens and other secretagogues in horses with recurrent airway obstruction (heaves) and clinically normal horses before and after exposure to moldy hay.5 horses with heaves and 5 clinically normal horses.Heaves was characterized as an increased clinical respiratory score and maximum change in transpulmonary pressure of20 cm H2O after exposure. Bronchoalveolar lavage was performed during each period. Washed and resuspended cells were exposed for 20 minutes at 37 C with whole reconstituted freeze-dried preparations of Aspergillus fumigatus, Alternaria tenuis, and Ambrosia elatior, fungal extracts of Aspergillus fumigatus, Alternaria tenuis, and Micropolyspora faeni; A23187; and compound 48/80. Histamine release (HR) was used as a marker of degranulation.Compared with clinically normal horses, HR was significantly greater from PMC from horses with heaves during remission and exacerbation in response to whole preparations and extracts of Aspergillus fumigatus and whole preparations of Alternaria tenuis. Extracts of Alternaria tenuis caused significantly greater HR from PMC from horses with heaves during exacerbation. Histamine was also released from PMC in response to A23187 and to changes in osmolality of the medium, but only as a result of cell lysis by compound 48/80.Increased degranulation of PMC after antigenic challenge may contribute to the pathogenesis of heaves in horses.Strategies for prevention and treatment that attenuate degranulation of PMC may assist in the clinical management of horses with heaves.

Nerve growth factor (NGF) is well recognized to have a number of potent effects on mast cells, including increasing mast cell numbers in vivo and inducing mast cell degranulation in vitro. More recently, NGF has been demonstrated to induce PGD2 production by mast cells through the induction of mast cell cyclooxygenase expression. We have observed that NGF at doses as low as 10 ng/ml will induce IL-6 production and inhibit TNF-alpha release from rat peritoneal mast cells in the presence of lysophosphatidylserine as a cofactor. NGF synergizes with LPS treatment of peritoneal mast cells (PMC) for the induction of IL-6. Examination of the mechanism of this phenomenon has revealed that NGF can induce both rat PMC and mouse bone marrow-derived cultured mast cells to produce substantial levels of PGE2. This response is maximal at later time points 18-24 h after NGF activation. The ability of NGF to induce PGE2 is not dependent on mast cell degranulation. Other stimuli capable of inducing IL-6, such as LPS, do not induce production of this prostanoid. Inhibition of cyclooxygenase activity by PMC using either flurbiprofen or indomethacin inhibited both the NGF-induced PGE2 synthesis and the NGF-induced alterations in TNF-alpha and IL-6 production. These results suggest a role for mast cell-derived prostanoids in the regulation of local inflammatory responses and neuronal degeneration after tissue injury involving induction of NGF production.

Sections of the lower trachea of cattle, fixed in either Carnoy's or formalin, were stained with toluidine blue, alcian blue, or alcian blue and safranin O to study the mast cell population. After toluidine blue staining, about twice as many cells in tissue fixed in Carnoy's contained dark blue granules compared with tissue fixed in formalin. In addition, for the first time in cattle, a population of cells containing red granules was identified after staining with alcian blue and safranin O. Most of these red granules were formalin sensitive. An enzymatic dispersal technique for mast cells is described that yielded 9.4+/-0.4% mast cells (percentage of nucleated cells) with a viability of 92.3+/-0.6%. Spontaneous histamine release was 3.3+/-0.8%. Dispersed mast cells were challenged with various immunological and nonimmunological secretagogues. The calcium ionophores, A23187, ionomyocin, and BrX537A, were effective in releasing up to 94% of histamine in mast cells in a dose-response relationship. Pasteurella haemolytica culture supernate caused about 10% histamine release at a dose of 0.5 mg/mL after correction for spontaneous release. The average histamine content of the mast cells was 6.6+/-1.0 pg/cell. Cytospins of dispersed cells fixed in Carnoy's and stained with alcian blue and safranin O contained mast cells with blue and red granules, and a few cells with a mixture of both granule types. Based on the effects of type of fixation, staining characteristics and histamine content, a mix of subtypes of mast cells is present in the bovine trachea. However, functionally they respond to secretagogues differently than rodent mast cells. Without an immunological secretagogue, studies to determine compounds that will be effective in blocking mast cell degranulation will be limited.

The asebia mouse represents a spontaneous mutation in BALB/c mice leading to hyperplasia of the epidermis and chronic inflammatory dermal changes including enhanced cellularity, oedema and elevated mast cell numbers. We demonstrated that asebia mice have constitutively elevated intercellular adhesion molecule-1 (ICAM-1) mRNA expression, which is not detectable in the wild type, and that dermal mast cell numbers were 3.1-fold higher than the wild type (P0.001). We utilized this model to explore the anti-inflammatory effects of cyclosporin A (CsA). After 3 weeks subcutaneous injection with 5 or 10 mg/kg CsA the expression of ICAM-1 mRNA was determined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and was found to be decreased 2.7-fold (P0.001) and three-fold (P0.001) relative to controls for 5 and 10 mg/kg treatments, respectively. Dermal mast cell counts were dose-dependently decreased by CsA. Mast cells, visualized by toluidine blue staining, decreased 4.5-fold with 10 mg/kg CsA (P0.001) bringing them down to numbers typical of the wild type. CsA also appeared to stabilize mast cell histamine content. Histological examination of haematoxylin-eosin-stained sections revealed that CsA treatment restored the wild-type skin phenotype decreasing epidermal hyperplasia, dermal cellularity and oedema. Thus, CsA exhibits a wide range of anti-inflammatory effects including reduction of ICAM-1 expression and mast cell numbers, and may be useful in the treatment of mast cell-mediated dermatoses.

Mast cells have been reported to secrete a wide range of immunoregulatory cytokines following IgE-mediated activation and to play an important role in allergic inflammation. We have previously demonstrated that mast cells can also produce certain cytokines following activation with bacterial LPS or prostanoids without preformed mediator release. IL-12 is a potent inducer of IFN-gamma production by T cells and NK cells, and is thought to play a critical role in determining the nature of the local immune response to infection. We here report that highly purified peritoneal mast cells from Brown Norway rats will produce IFN-gamma in response to IL-12 without significant histamine release. IFN-gamma protein was detected by ELISA in supernatants of mast cells cultured with 2 U/ml recombinant mouse IL-12 for between 6 and 24 h. The production of IFN-gamma was dependent on the dose of IL-12 and was significantly inhibited by concurrent treatment with IL-10 or PGE2. Supernatants from IL-12-stimulated mast cells induced MHC class II expression on the mouse epithelial cell line, MODE-K, by an IFN-gamma-dependent mechanism. Peritoneal mast cells cultured following activation with anti-IgE or LPS, under conditions that will induce the production of IL-6, demonstrated no detectable protein production of IFN-gamma. We conclude that mast cells are capable of contributing to the IFN-gamma response to IL-12, but substantial mast cell IFN-gamma production does not occur as a result of IgE-mediated activation. These observations have important implications for the role of the mast cell in local immune regulation.

Mast cells are traditionally associated with an acute response involving the short-term release of mediators such as histamine. We have shown previously that mast cells can produce IL-6 without prior histamine release. In this study we examined the hypothesis that mast cell IL-6 production can be selectively regulated by PGs. Highly purified rat peritoneal mast cells were cultured in the presence of PGE1, PGE2, or PGD2 alone or in combination with anti-IgE or bacterial LPS. Histamine release was assessed after 10 min; IL-6 and TNF-alpha production was measured in supernatants after 18 h. Mast cell IL-6 production was induced by PGE1 and PGE2 to a similar level to that observed in anti-IgE-activated cells. In contrast, constitutive production of TNF-alpha was inhibited by PGE1 and PGE2, but not by PGD2. PGE2 had a synergistic effect, inducing IL-6 in the presence of LPS, whereas an additive effect was observed in the presence of anti-IgE. None of the prostanoids alone induced significant histamine release at the 10-min time point. However, PGE2 significantly increased histamine release when added concurrently with anti-IgE. Flurbiprofen in the context of anti-IgE or LPS activation did not alter mast cell IL-6 or TNF-alpha production. IL-6 production in response to each of the stimuli was significantly inhibited by the corticosteroid dexamethasone. These observations of selective modulation of mast cell cytokine production are important to understand the mechanisms by which mast cells interact with other cells during an inflammatory process involving prostanoid synthesis.

Cholera toxin (CTX) is a potent oral adjuvant for the induction of mucosal IgA Ab responses protein Ags. We examined the Ab responses and allergic sensitization of several strains of mice to protein Ags, administered orally with CTX. The mice made strong IgA and IgG1 serum Ab responses, but little IgG2a Ab to Ags such as hen egg lysozyme (HEL) and OVA. However, when given a subsequent i.p. challenge with Ag alone, the same mice had immediate hypersensitivity reactions that included respiratory distress and death. Within 10 min of i.p. challenge, immunized mice had high levels of plasma histamine and extensive degranulation of mast cells in target tissues. These mice had detectable serum IgE Ab. Ag administered orally with the B subunit (CTB) of CTX did not sensitize mice. Intestinal tissues taken from these mice had Ag-specific ion-secretory responses in vitro, typical of intestinal anaphylaxis. Ag given s.c. without adjuvant could also sensitize for systemic and intestinal anaphylaxis. Sensitization with HEL given s.c. was dose dependent and correlated with a critical amount of HEL in the circulation. HEL was detected in the circulation after oral immunization, but CTX did not increase the uptake of HEL. Thus, oral immunization with a protein Ag in the presence of CTX can sensitize an animal for systemic and intestinal anaphylaxis. These results suggest a cautious approach to the use of CTX as an adjuvant in oral vaccines, and provide a new model to study immediate hypersensitivity reactions to intestinal Ag.

Mast cells produce a number of cytokines including IL-6. In view of the large amounts of de novo synthesis induced by the activation of rat peritoneal mast cells and previous observations of expression of this cytokine by human lung mast cells, we have studied the regulation of IL-6 production. We examined the hypothesis that mast cell IL-6 production is not related to previous histamine release. Highly purified rat peritoneal mast cells were activated with anti-IgE, calcium ionophore A23187, or LPS. Histamine was used as a marker of preformed mediator release and IL-6 production was assessed by using the B9 hybridoma growth factor bioassay. Anti-IgE activation of rat peritoneal mast cells induced IL-6 production and histamine release. In contrast, LPS activation induced substantial, serum-dependent, IL-6 production without a significant level of histamine release. No preformed IL-6 was detected in the cells. Calcium ionophore induced histamine release from mast cells to a greater extent than did anti-IgE, but no A23187-induced IL-6 production was observed. A23187-treated cells retained high viability and produced a significant amount of TNF-alpha. To further examine the concordance of IL-6 production and histamine release we used mast cell stabilizing drugs. Dexamethasone and nedocromil significantly inhibited IL-6 production in response to anti-IgE. Our results demonstrate that there is not a direct relationship between mast cell degranulation and IL-6 production. Our observations are important for understanding the role of mast cells in inflammation and for developing strategies to modulate mast cell function in disease.

Three hundred twenty-four carotid endarterectomies (CEAs) were performed on 303 patients over 5 years. Sixty per cent of the patients were symptomatic with completed stroke (36.4%), amaurosis fugax (35.4%) or transient ischemic attack (TIA) (50.5%). Some patients had multiple symptoms. Perioperative stroke occurred in four patients (1.2%) and 30-day mortality in five (1.5%). The combined stroke-mortality rate was 2.8 per cent. Other postoperative complications included TIA (1.9%), cranial nerve injury (3.1%), wound hematoma (6.5%), and hypertensive reperfusion syndrome (9.6%). Ten early reoperations were performed for wound hematoma (7) or technical problems (3). Follow-up of 284 CEAs (88%) at a means of 31 months revealed 33 late deaths, with two due to stroke. Late strokes occurred in 11 patients (3.9%). Five late strokes were ipsilateral (1.8%) and six were contralateral (2.1%) to the operated carotid artery. Ninety-seven carotid arteries were evaluated by duplex ultrasound scanning at a mean postoperative interval of 27.2 months. Ninety-two per cent had 0-30 per cent restenosis, 5 per cent had 40 per cent to 60 per cent restenosis and 3 per cent had 70 per cent or greater restenosis. The authors conclude that CEA can be performed with acceptable morbidity and mortality rates and that it is a durable operation that reduces the risk of late stroke.

These case reports describe two patients with acquired immune deficiency syndrome (AIDS) who presented with acute right lower quadrant pain. Appendiceal involvement with Kaposi's sarcoma accounted for the clinical presentation, and was confirmed histologically. This association emphasizes the diagnostic confusion that may be caused by acute abdominal conditions in the AIDS population. Abdominal pain may result from AIDS-related or unrelated processes; appropriate operative intervention requires recognition of the various diagnostic possibilities.

Three hundred eleven patients with node-positive breast cancer were randomized to one of three adjuvant treatments: cyclophosphamide (Cytoxan), methotrexate, and 5-fluorouracil; all of the above with tamoxifen citrate; or all of the above with tamoxifen and bacillus Calmette-Guerin vaccination. Local therapy for all patients was a modified radical mastectomy. Estrogen receptors were measured on all primary tumors. Patients were stratified by the number of positive nodes (one to three nodes and more than three nodes) and estrogen-receptor value (less than 3 femtomole/mg and greater than or equal to 3 femtomole/mg). Follow-up is available, with a mean of 9.1 and maximum of 14.2 years. In this study the efficacy of short-term tamoxifen is apparent over that of chemoimmunotherapy alone and continues to be significant with prolonged follow-up. The addition of tamoxifen to chemoimmunotherapy significantly prolonged disease-free survival among patients with estrogen receptor-positive tumors who were postmenopausal, who had larger tumors (greater than 3 cm), or who had more extensive axillary node involvement (more than three nodes). Tamoxifen improved overall survival for patients with estrogen receptor-positive tumors larger than 3 cm. The addition of bacillus Calmette-Guerin Cytoxan, methotrexate, 5-fluorouracil, and tamoxifen did not significantly alter disease-free or overall survival.

A variety of mast cell degranulating agents have previously been shown to induce mast cell hyperplasia in adult rats. In neonates 2.5 S nerve growth factor (NGF) induces a hyperplasia of both mucosal and connective tissue mast cells (MMC and CTMC). We have examined the role of the potent mast cell degranulating properties of NGF on its ability to induce mast cell hyperplasia. Administration of NGF in combination with the mast cell stabilizing agent disodium cromoglycate was found to abrogate the CTMC hyperplasia induced by NGF alone. Treatment of neonatal rats with the alternate degranulating agent compound 48/80 was found to induce a limited CTMC but not a MMC hyperplasia. A supernatant obtained by degranulating purified adult rat peritoneal mast cells with anti-IgE was found to induce hyperplasia of the CTMC population similar to that observed with NGF administration. However, this degranulation product supernatant only induced a limited MMC hyperplasia as judged by RMCP II content of the tissues. These results suggest that NGF has dual action inducing mast cell hyperplasia; CTMC hyperplasia being dependent on the ability of NGF to degranulate mast cells. MMC hyperplasia induced by NGF is independent of CTMC degranulation. Degranulation products from peritoneal mast cells act to increase both MMC and CTMC populations in the neonate. These data suggest that the CTMC population may be regulated by an autocrine positive feedback mechanism in vivo.

Two 3-week experiments with small enclosures were conducted in situ in northeastern Green Bay, Lake Michigan, to compare the effects of separate and combined additions of cadmium and zinc on the zooplankton community. The radioisotopes 109Cd and 65Zn were used as tracers to determine the sorption of cadmium and zinc by different particle size fractions. Separate additions of 2 μg Cd/L or 100 μg Zn/L, as well as combined additions of 2 μg Cd/L + 100 μg Zn/Lor 1 μg Cd/L + 50 μg Zn/L, caused significant reductions of total crustacean density, species diversity, two community similarity indices, and final dissolved oxygen concentration. The effects of separate additions of 100 μg Zn/L were generally more pronounced than those of 2 μg Cd/L, but were similar to those of ∼5 μg Cd/L. The effects of combined additions of 2 μg Cd/L + 100 μg Zn/L were not significantly different from those of 100 μg Zn/Lalone and were primarily due to zinc because it reduced cadmium uptake by the plankton (10–85 μm and >85 μm fractions). The effects of combined additions of l μg Cd/L + 50 μg Zn/L probably were also mainly due to zinc. The overall results of this study suggest that less than a ten-fold increase in the concentration of zinc in Lake Michigan (presently ∼5 μg/L) could have pronounced effects on the plankton community.

A mathematical model widely applied in population studies and in assessment of the impact of exploitation on fish populations was applied to assess cadmium toxicity in laboratory populations ofDaphnia galeata mendotae. Over a range of toxicant concentrations, the birth rate of the population increased to balance the death rate and the population compensated for the increased mortality. The model describes the relation between toxicant concentration, toxicant-induced mortality, and equilibrium population size. Compensation for increased mortality is described in terms of the decrease in population size necessary to produce an increase in the birth rate that will balance the increased death rate. The relative capacity of different aquatic organisms to compensate for toxicant-induced mortality is examined and a relation between compensatory capacity and the innate capacity for increase is developed.

Four in situ experiments with small-volume (28-L) enclosures were conducted in Experimental Lakes Area Lake 382 to assess the effects of inorganic mercury and cadmium on the plankton community. Additions of 0.9 × 10−8 mol Cd/L caused significant reductions of crustacean zooplankton density, zooplankton community similarity, zooplankton species diversity, and dissolved oxygen concentration over 3-wk periods. Additions of 1.0 × 10−8 mol Hg/L caused reductions similar to those of 0.9 × 10−8 mol Cd/L. Phytoplankton primary productivity was reduced by additions of 2.0 × 10−8 mol Hg/L but not by 1.0 × 10−8 mol Hg/L. On a molar concentration basis, the toxicities of inorganic mercury and cadmium were quite similar. Significant changes in lake plankton communities may occur at molar concentrations above 0.2 × 10−8 mol/L. Potentially toxic concentrations of cadmium may occur in many contaminated lakes, but toxic concentrations of mercury probably occur in few lakes.Key words: Precambrian Shield lakes, plankton communities, phytoplankton, zooplankton, cadmium, mercury toxicity

Recent estimates suggest that inputs of Zn and Cd to southern Lake Michigan exceed losses. We investigated the sorption and sedimentation of Zn and Cd by southern Lake Michigan seston particles using 65Zn and 109Cd in 21 radiotracer experiments. The time-series sorption by total seston >0.45 μm was asymptotic with apparent equilibria of ∼100–200 ng Zn/L and ∼1.0–2.0 ng Cd/L, occurring in ∼24–30h during the summer phytoplankton bloom. Studies of the sorption by different particle size fractions showed that the abundance of phytoplankton and detritus control the concentrations of particle-bound Zn and Cd. The seasonal maximum concentrations of particle-bound Zn and Cd correlated well with the development of both the summer and fall phytoplankton blooms. Serial additions of Zn and Cd in combination with the radiotracers showed that these additions inhibit the sorption of both metals as their toxic effects are expressed. Coupling of the particle-bound Zn and Cd estimates for the period May to December with data on the seasonal variations in the net settling velocity in southern Lake Michigan provided annual sedimentation rates of ∼9 μg Zn/cm2.yr and ∼0.1 μg Cd/cm2 yr that are in excellent agreement with similar estimates by other investigators. Likewise, dividing our particle-bound estimates by the dry weight of total seston in the samples provided sediment concentration estimates of ∼38–185 ng Zn/mg dry weight (ppm) and 0.5–2.3 ng Cd/mg dry weight that agree with measured levels from the surficial Lake Michigan sediment. The results of these experiments suggest that, if the dissolved concentrations of Zn and Cd do increase to toxic levels, the impacts on phytoplankton may potentiate further increases in the dissolved levels by reducing plankton sorption and removal by sedimentation.

We conducted four in situ experiments in the southern basin of Lake Michigan to determine the responses of the plankton community to additions of cadmium (3 μg/L) and zinc (15, 30, 60, and 90 μg/L) as well as the bioaccumulation of zinc by different species of crustacean zooplankton. Total cadmium and zinc concentrations in treated enclosures (accounting for pretreatment lakewater concentrations of ~ 20 ng Cd and ~ 1 μg Zn per litre) were calculated from measurements of 109Cd and 65Zn with known specific activities.Zinc significantly reduced zooplankton populations and several other properties of community structure and function at concentrations much lower than those previously reported to be toxic to zooplankton and well below the levels established for protection of freshwater life. Zinc additions as low as 15 μg/L significantly reduced chlorophyll a, primary productivity, dissolved oxygen, specific zooplankton populations, zooplankton species diversity, and community similarity within 2 wk. Populations of several zooplankton species were severely reduced by 15 μg/L; for example, the population of the rotifer Conochilus unicornis was reduced to less than 1% of that in controls. Secondary, indirect effects included significant increases of a few populations, including Bosmina longirostris and Keratella cochlearis, for zinc additions of 15 and 30 μg/L. Most of the populations and community properties that we measured showed somewhat different percentage reductions in response to a given zinc addition at different times, but their relative (rank) values at different times were similar. Specific zooplankton populations were more sensitive to zinc than community similarity indices, and species diversity indices were relatively insensitive. Bioaccumulation of zinc by different species of crustaceans increased with added zinc but showed few significant differences among species. The small differences among species could, nevertheless, partially account for some of the observed changes in zooplankton community structure.

Radar maps of precipitation at a height of 6 km have been studied for the thunderstorms of one July day. Regions on these maps within which the intensity level exceeds 30 dBZ (corresponding to a rainfall rate of 2.8 mm h−1) represent thunderstorms, some single-celled and some multi-celled. These were found to be the sources of lightning observed (as “sferics”) by a radio direction finder, frequency 100±50 kHz, located at the radar. The sferics rates of the storms were related closely to other storm parameters by L = 2.7A1.64r−1.62,where L is the number of sferics observed per minute, r the distance of the storm (km), and A the area (km2) of the storm region as specified above. This study supports the findings of Larsen and Stansbury for an earlier day (J. Atmos. Terr. Phys., 1974, 36, 1547–1553) and adds the algebraic relation.

A hypothetical array of terrestrial microwave links has been designed at radar ranges 36 to 110 km and all azimuths, such that useful attenuation statistics can be derived from the weather-radar record on digital tape of the few hours' passage of one storm system across the array. These statistics cannot be used as the basis for design in the way that the data for a whole season might be used, but one can compare one storm with another, and hope to relate attenuation to meteorological aspects of the storm. From one case of a line of intense storms it has been found that: (i) Total duration of attenuation in excess of A decreased approximately exponentially with increasing A for a given link length, and for a given value of A increased approximately linearly with link length, at any rate up to 48 km. (ii) Durations varied with link direction, but less than ±20%. (iii) Individual fades of attenuation in excess of A were more numerous but more brief for links perpendicular to the direction of motion of the precipitation pattern than for those parallel. (iv) “Synthetic links” based on raingauge data have statistics like links parallel to the direction of pattern motion. Thus they are representative of links generally for “total duration” statistics (see i) where direction is unimportant (see ii) but not for individual-fade duration and frequency (see iii). These findings for one storm passage were confirmed by two others: a less intense line and a case of widely scattered light showers.

Structural and functional responses of plankton communities to cadmium stress were studied during 1977 in Lake Michigan using small-volume (8 L) completely sealed enclosures, and in Canada's Experimental Lakes Area (ELA) Lake 223 using large-volume (1.5 × 105 L) open-surface enclosures. In Lake Michigan, reductions of the average abundance of micro-crustaceans by cadmium were significantly greater in "light" or shallow epilimnetic incubations than they were in "dark" or deep epilimnetic incubations. Measurements of dissolved oxygen indicated that this interaction with light (depth) was an indirect effect due to a reduction of photosynthesis and primary production. Zooplankton density and species diversity were not significantly affected within 21 d by cadmium concentrations [Formula: see text] and [Formula: see text] Cd/L, respectively, whereas final dissolved oxygen concentration and percentage similarity (PS) of the crustacean zooplankton community were significantly reduced by [Formula: see text] Cd/L. In the ELA Lake 223 experiment, the reducing effect of cadmium on zooplankton density increased up to 31 d after Cd enrichment and then decreased, probably due to decreasing Cd concentrations in the water. Values of PS on day 24 for the ELA enclosures enriched with 1 and 3 μg Cd/L were within the 95% confidence limits for individual values predicted from a regression of PS on cadmium for the 21-d Lake Michigan experiments.Key words: plankton communities, zooplankton, phytoplankton, cadmium stress, Lake Michigan, Canadian Shield lakes

Forty populations of Daphnia galeata mendotae were maintained for 22 wk (or until they became extinct) in a medium consisting of filtered Lake Michigan water to which Chlamydomonas reinhardi and different concentrations of a mixture of labelled (109Cd) plus stable CdCl2 were added 24 h before use. The medium was changed daily Monday through Fridays. Weekly determinations were made of total numbers, average individual dry weight, mean brood size, egg–female ratio, aborted eggs and embryos, and average whole-body 109Cd content. Chronic cadmium stress reduced the populations' average numbers and biomass, while it increased the populations' turnover rates, temporal variability, probability of extinction, and proportion of ovigerous females. For individuals there was increased prenatal mortality, reduced life expectancy, increased average weight, and increased brood size. Due to compensatory increases in the proportion of ovigerous females and mean brood size, the cadmium sensitivity of population attributes was considerably less than that of the most sensitive individual attribute, prenatal mortality. A linear relationship between population carrying capacity (relative mean numbers) and added cadmium concentration indicated that the effective concentration for a 50% reduction of carrying capacity (EC50) is 7.7 μg Cd/L and that for a 1% reduction (EC1) is 0.15 μg Cd/L. An increase of 0.15 μg Cd/L in Lake Michigan itself, barring synergistic interaction with other factors in the lake, would probably not have a detectable effect on the population dynamics of D. galeata mendotae. Key words: zooplankton dynamics, stress ecology, Daphnia galeata mendotae, cadmium, heavy metals, toxic substances, Laurentian Great Lakes

The surplus production model is a simple and easily applied model for the assessment of environmental impacts on exploited fish populations. However, its application requires several assumptions about the relationships between the degree of impact and the population response that are difficult to test using field data. To examine these assumptions, the model is applied to exploited laboratory populations of Daphnia pulex exposed to chronic radiation stress. The model describes the observed relationship between equilibrium population size and the level of radiation exposure. It also describes the relationship between yield and population size.

Shape factors for scattering and attenuation in precipitation are normally less than 2, because raindrops are not normally distorted much, and because snow or ice crystals, though distorted, have a relatively small dielectric constant. Very distorted water drops would have large shape factors because of the great dielectric constant of water. A thin water coating, however, raises the attenuation by an ice sphere up to or beyond that of a water sphere, and the scattering, nearly up to that of a water sphere. If, similarly, it raises attenuation and scattering by a non-spherioal ice particle to that of a similarly shaped water particle, then the shape factors for spheroidal water drops are good approximations to the shape factors for randomly oriented wet ice crystals. This is based on the assumption that the theory of small spheroids can still be applied when the particle is comparable with the wavelength and that the results on water coatings apply to spheroids as well as to spheres. A full theoretical investigation of these assumptions would be a heavy undertaking, and exper1mental verification appears preferable. If these assumptions are justified the scattering of melted snow would exceed that of rain of the same precipitation rate and the attenuation would rise to many times that of rain.

A new PPI map is made up of 600 radial lines, each of 100 dots. Each dot is in one of six shades of grey, thus indicating target intensity, and dot size varies somewhat with shade. Each dot combines k independent data, where 7 < k < 75, and the data were combined by taking (electronically) the peak reading among the k data. The data from these maps were processed further by counting the fraction of a group of about 20 dots that had a given shade, i.e., that fell in a given echo-intensity interval. This procedure yields improved intensity resolution, on a scale of intensity level that is practically continuous (surprisingly, since only a few spaced thresholds are used) at the expense of spatial resolution.

A characteristic “mares' tail” pattern of falling snow (observed in vertical section by radar) suggests that the snow is generated continuously, in compact generating elements; the pattern results from the snow's falling at constant velocity through the wind shear. For constant wind shear, the snow trails are parabolic, and before reaching the ground become almost horizontal. The velocity of the pattern is that of the generating elements, and can be compared with wind strengths aloft to locate the height of the generating elements when these elements are not detected by the radar.