Spatiotemporal analysis of lake chlorophyll-a with combined in situ and satellite data.

We estimated chlorophyll-a (Chl-a) concentration using various combinations of routine sampling, automatic station measurements, and MERIS satellite images. Our study site was the northern part of the large, shallow, mesotrophic Lake Pyhäjärvi located in southwestern Finland. Various combinations of measurements were interpolated spatiotemporally using a data fusion system (DFS) based on an ensemble Kalman filter and smoother algorithms. The estimated concentrations together with corresponding 68% confidence intervals are presented as time series at routine sampling and automated stations, as maps and as mean values over the EU Water Framework Directive monitoring period, to evaluate the efficiency of various monitoring methods. The mean Chl-a calculated with DFS in June-September was 6.5-7.5 µg/l, depending on the observations used as input. At the routine monitoring station where grab samples were used, the average uncertainty (standard deviation, SD) decreased from 2.7 to 1.6 µg/l when EO data were also included in the estimation. At the automatic station, located 0.9 km from the routine monitoring site, the SD was 0.7 µg/l. The SD of spatial mean concentration decreased from 6.7 to 2.9 µg/l when satellite observations were included in June-September, in addition to in situ monitoring data. This demonstrates the high value of the information derived from satellite observations. The conclusion is that the confidence of Chl-a monitoring could be increased by deploying spatially extensive measurements in the form of satellite imaging or transects conducted with flow-through sensors installed on a boat and spatiotemporal interpolation of the multisource data.

Tropospheric Emissions: Monitoring of Pollution (TEMPO).

TEMPO was selected in 2012 by NASA as the first Earth Venture Instrument, for launch between 2018 and 2021. It will measure atmospheric pollution for greater North America from space using ultraviolet and visible spectroscopy. TEMPO observes from Mexico City, Cuba, and the Bahamas to the Canadian oil sands, and from the Atlantic to the Pacific, hourly and at high spatial resolution (~2.1 km N/S×4.4 km E/W at 36.5°N, 100°W). TEMPO provides a tropospheric measurement suite that includes the key elements of tropospheric air pollution chemistry, as well as contributing to carbon cycle knowledge. Measurements are made hourly from geostationary (GEO) orbit, to capture the high variability present in the diurnal cycle of emissions and chemistry that are unobservable from current low-Earth orbit (LEO) satellites that measure once per day. The small product spatial footprint resolves pollution sources at sub-urban scale. Together, this temporal and spatial resolution improves emission inventories, monitors population exposure, and enables effective emission-control strategies. TEMPO takes advantage of a commercial GEO host spacecraft to provide a modest cost mission that measures the spectra required to retrieve ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), formaldehyde (H2CO), glyoxal (C2H2O2), bromine monoxide (BrO), IO (iodine monoxide),water vapor, aerosols, cloud parameters, ultraviolet radiation, and foliage properties. TEMPO thus measures the major elements, directly or by proxy, in the tropospheric O3 chemistry cycle. Multi-spectral observations provide sensitivity to O3 in the lowermost troposphere, substantially reducing uncertainty in air quality predictions. TEMPO quantifies and tracks the evolution of aerosol loading. It provides these near-real-time air quality products that will be made publicly available. TEMPO will launch at a prime time to be the North American component of the global geostationary constellation of pollution monitoring together with the European Sentinel-4 (S4) and Korean Geostationary Environment Monitoring Spectrometer (GEMS) instruments.

Long-term functional outcome after restorative proctocolectomy in patients with ulcerative colitis.

AIM: The aim of this study was to evaluate the long-term functional outcome of ileal pouch-anal anastomosis for ulcerative colitis and to compare symptoms over time. METHODS: In all, 188 patients were operated with an ileal pouch-anal anastomosis. Short-term functional outcome has previously been evaluated with a symptom questionnaire. The same questionnaire was sent to the 162 patients who were alive and had an intact pouch. A symptom index was studied over time and in relation to early complications and pouchitis. RESULTS: The response rate of the questionnaire was 139/162 at a median of 12.5 (9.5-21) years postoperatively. Overall, the symptom index remained unchanged over time but both the frequency of night-time defaecation and episodes of night-time incontinence increased. Patients' global assessment was unchanged with approximately 80% stating an excellent or a good result. Frequency of pouchitis doubled in 10 years. Symptom index for patients with episodic pouchitis [median 40 (8-89), P = 0.018] and recurrent/chronic pouchitis [71 (8-136), P < 0.001] was higher than in patients without pouchitis [29 (0-105)]. Early complications did not affect the symptom index. CONCLUSION: The overall functional outcome of ileal pouch-anal surgery for ulcerative colitis is stable over time. Patients' satisfaction with outcome remains high. Pouchitis is a determinant of functional outcome.

Influence of early and current environmental exposure factors on sensitization and outcome of asthma in pre-school children.

BACKGROUND: Exposure to furred pets in early life has been considered to increase the risk of allergic sensitization and consequent development of asthma later in children. However, recently, it has been suggested that early exposure to pets prevents sensitization. The aim of this study was to evaluate the importance of early exposure to pets and other environmental risk factors in asthmatic children. METHODS: This is a follow-up study after 2 years of a previously investigated group of 193 asthmatic children, aged 1-4 years. The study was completed by 181 children, who were clinically examined; serum IgE antibodies were also measured and a questionnaire was answered. RESULTS: Children with reported exposure to cats during the first 2 years of life were more likely to have developed sensitization to cat by 4 years of age than unexposed children. High levels of cat allergen (Fel d 1> or =8 microg/g dust) were associated with an increased risk of sensitization to cat and, in combination with tobacco smoke, also with the development of more severe asthma. CONCLUSION: In young asthmatic children, early exposure to cat and tobacco smoke increased the risk of allergic sensitization and further development of more severe asthma later in childhood.

cAMP mediated upregulation of CYP2A5 in mouse hepatocytes.

CYP2A5 is induced by a large number of chemicals including some cAMP modifiers. In a primary hepatocyte model, stimulation of the cAMP signal transduction pathway by glucagon and isoproterenol, acting via specific G-protein coupled plasma membrane receptors, produced up to 17-fold increases in the marker activity of CYP2A5, coumarin 7-hydroxylase. In contrast, glucagon and isoproterenol caused no significant effects on two other major CYP forms, CYP2B10 and CYP1A1/2. Phenobarbital (PB) elicited a 3-fold increase in CYP2A5 expression (catalytic activity and mRNA), while the cAMP and protein kinase A (PKA) stimulators dibutyryl-cAMP, forskolin and Sp-cAMPs caused up to 18-fold increases in the amount of CYP2A5 mRNA. Coadministration of PB and cAMP/PKA stimulating agents produced an additive inducing effect. The expression of CYP2A5, but not CYP2B10 or CYP1A1/2, in DBA/2 mice displayed a marked circadian rhythm, the level of expression being highest in the evening. These results suggest that among xenobiotic metabolizing CYP enzymes, CYP2A5 is uniquely upregulated by cAMP, possibly having the physiological function of priming the olfactory and digestive systems for nocturnal feeding.

CYP2A5/CYP2A6 expression in mouse and human hepatocytes treated with various in vivo inducers.

Induction of coumarin 7-hydroxylation, catalyzed by CYP2A5 in mice and CYP2A6 in humans by various known in vivo murine inducers and modifiers, was compared in human and mouse hepatocytes in culture. Phenobarbital and rifampicin were efficient inducers (up to 10-fold induction) after 48-h treatment in murine cultured hepatocytes, whereas the enzyme activity in human hepatocytes was much more refractory to induction. However, a prolongation of incubation time to 72 h in human hepatocytes led to a modest restoration of inducibility by phenobarbital. Of the three porphyrinogenic inducers studied, griseofulvin induced the murine enzyme efficiently, but not the human enzyme, whereas aminotriazole and thioacetamide had no effect on either species. Pyrazole produced substantial induction in both human and murine hepatocytes, whereas cobalt chloride, which is also an in vivo inducer of the mouse enzyme, had no effect. Clofibric acid, an in vivo depressor of coumarin 7-hydroxylase, also depressed hepatocyte activities. In both murine and human hepatocytes, changes in CYP2A5/6 mRNA levels correlated roughly with enzyme changes, except in the case of cobalt chloride, which increased mRNA levels despite a lack of effect on enzyme activity. In general, human and mouse hepatocytes gave a similar response to CYP2A inducers. However, some differences were found, which means that, although CYP2A isozymes are probably regulated in a similar manner in both species, it is necessary to be cautious before extrapolating to human the results found in mouse models.

Influence of interaction of environmental risk factors and sensitization in young asthmatic children.

BACKGROUND: The increasing prevalence of asthma and allergy in many countries demands evaluation of potential risk factors to improve the possibility of prevention. OBJECTIVE: We studied the association between exposure to cat and dog allergen and allergic sensitization in young children with asthma and interactions with potential environmental risk factors. METHODS: One hundred eighty-nine young children with asthma were evaluated. IgE antibodies to cat and dog were analyzed. Questionnaires were filled in focusing on exposure to cats and dogs, environmental tobacco smoke (ETS), and signs of home dampness as indicated by window pane condensation (WPC) during the first years of life. House dust was analyzed for content of cat (Fel d 1) and dog (Can f 1) allergen. RESULTS: There was a strong association between the degree of reported exposure to cat and dog and the concentration of the respective allergens in floor dust. A dose-response relationship was found between cat exposure, measured as either reported degree of cat exposure or cat allergen levels in dust, and sensitization both to cat and dog. No such relationship was found between exposure and sensitization to dog. WPC increased the risk for sensitization to cat (odds ratio = 2.6, 95% confidence interval 1.2-5.8), whereas ETS strongly tended to do so both to cat and dog. Interaction was found between exposure to ETS, WPC, and high levels of cat allergen (>8 microg/g dust). The presence of all 3 risk factors revealed a multiplicative interaction with a high risk of sensitization to cat (odds ratio = 42.0, 95% confidence interval 3.7-472.8). CONCLUSIONS: Keeping cats indoors may be a health hazard for infants and young children at risk for development of asthma, particularly when they live in a damp house and their parents smoke.

Immunotherapy in children with allergic asthma: effect on bronchial hyperreactivity and pharmacotherapy.

BACKGROUND: Immunotherapy has been shown to reduce allergen sensitivity to allergens such as cat and dust mite. The aim of this study was to investigate the effect of cat or dust mite immunotherapy on bronchial hyperreactivity and the need for inhaled corticosteroids in children with asthma, cat or dust mite allergy, and hay fever. SUBJECTS: Twenty-nine children, 7 to 16 years old, completed the 3-year study. They were randomly allocated to receive cat/dust mite or placebo and birch/timothy immunotherapy. METHODS: Before immunotherapy was begun and then once each year, bronchial histamine challenges were performed. Bronchial allergen challenge with the perennial allergen was done before and after the 3-year study. Pharmacotherapy was given according to a standardized protocol. RESULTS: PC20 allergen increased significantly in both the active immunotherapy group (P <.001) and in the placebo-pollen group (P <.05). PC20 histamine increased continuously in the active immunotherapy group (P <.05 and P =.002 after 1 and 3 years, respectively) and had also increased after 3 years in the placebo-pollen group (P <.05). The difference between the 2 groups was significant for PC20 allergen (P =.001) but not for PC20 histamine. There was no significant change in the dose of inhaled budesonide needed for symptom control in either of the groups. CONCLUSION: Pollen immunotherapy combined with inhaled corticosteroids results in improvement of both cat/dust mite bronchial sensitivity and hyperresponsiveness to histamine. The combination of cat or dust mite, pollen immunotherapy, and inhaled budesonide enhances this improvement. Cat immunotherapy also induces cat allergen tolerance.

Indoor environmental risk factors in young asthmatics: a case-control study.

One hundred and ninety three children with asthma and 318 controls aged 1-4 years were evaluated for atopic heredity and exposure to possible indoor risk factors for asthma-for example exposure to furred pets, tobacco smoke, and home dampness. A subgroup of cases were classified as cat and/or dog allergic on the basis of skin prick tests. Heredity for asthma was a significant risk factor (odds ratio (OR) 3.0, confidence interval (CI) 2.1 to 4.6). Environmental tobacco smoke was associated with an excess risk for asthma (OR 1.7, CI 1.1 to 2.3) and signs of home dampness tended to increase this risk (OR 1.3, CI 0.9 to 2.0). High dose exposure to cat and/or dog resulted in an increased risk only in asthma cases sensitised to cat and/or dog (OR 2.7, CI 1.0 to 7.3). A combination of high dose exposure to cat and/or dog, environmental tobacco smoke and damp housing was associated with an OR of 8.0 (CI 1.9 to 34.1). Raised indoor humidity has been shown to reflect low air exchange, which may also lead to increased doses of inhaled aeroallergens and tobacco smoke, and contribute to the interaction between the three risk factors.

Cytokine production in mononuclear cells of human milk studied at the single-cell level.

In this study, we demonstrate that mononuclear cells of human milk have a potential for production of many different cytokines. We applied a technique for cytokine detection at the single-cell level using cytokine specific MAb and immunofluorescence. The characteristic staining pattern obtained represents intracellular cytokine production, which allows for the assessment of the cellular origin of production. Milk mononuclear cells were mitogen-stimulated in vitro and cultured for 4 h and then stained for 13 cytokines. Lipopolysaccharide stimulation induced extensive production of the following monokines: IL-1 alpha, IL-1 beta, IL-1ra, IL-6, IL-8, and tumor necrosis factor-alpha. IL-10 and granulocyte-macrophage colony-stimulating factor were smaller products, although detectable in most samples. The abundant monokine production correlated with the high number of macrophages in milk. Spontaneous monokine production in unstimulated cells could be detected in six out of 11 samples. The highest incidence was evident for IL-8. No spontaneous lymphokine production was detected. Considering the low proportion of lymphocytes, stimulation with phorbol myristate acetate in combination with ionomycin resulted in considerable production of the following lymphokines: IL-2, IL-3, IL-4, IL-10, interferon-gamma, tumor necrosis factor-alpha. Macrophages contributed to the high production of tumor necrosis factor-alpha and GM-CSF. IL-5 synthesis was detectable in only one sample. This work reveals that human milk mononuclear cells are potent producers of cytokines when mitogen stimulated in vitro. The in vivo implications of these findings remain to be investigated further.

Rat acid phosphatase: overexpression of active, secreted enzyme by recombinant baculovirus-infected insect cells, molecular properties, and crystallization.

Rat prostatic acid phosphatase (rPAP; orthophosphoric-monoester phosphohydrolase (acid optimum), EC 3.1.3.2) was expressed in the baculovirus expression vector system. Recombinant protein was secreted into the medium at a high yield by infected insect cells, which were cultured at high density in a 30-liter bioreactor allowing high oxygen content for rapidly growing cells. About 20% of the cell protein produced was rPAP. Partial sequence determination of the N terminus of the purified recombinant secreted protein revealed identity to the native secreted protein, showing that the signal peptide is recognized and properly cleaved in insect cells. The enzyme was purified by using L-(+)-tartrate affinity chromatography. The purified protein had a high specific activity of 2620 mumol.min-1.mg-1 with p-nitrophenyl phosphate at the substrate, and it also showed phosphotyrosine phosphatase activity. The molecular mass of the recombinant rPAP was 155 kDa. Two subunits of 46 kDa and 48 kDa could be detected in SDS/PAGE, but only one subunit of 41 kDa was present after digestion with N-glycosidase. The active enzyme is a trimer of subunits differing only in glycosylation. When recombinant rPAP was crystallized with polyethylene glycol 6000 as the precipitant, the crystals were trigonal (space group P3(1)21) with cell dimensions a = 89.4 A and c = 152.0 A. The observed diffraction pattern extends to a resolution of at least 3 A.

Allergic symptoms up to 4-6 years of age in children given cow milk neonatally. A prospective study.

In a previously published prospective study, we followed the development of allergic symptoms in term infants with a slightly reduced birthweight (-1 SD to -2 SD). These children received, according to local routine, early feeding with cow milk formula in order to diminish such neonatal problems as hypoglycemia and hyperbilirubinemia. Of 216 infants 207 were observed for allergic symptoms up to 18 months of age. One group (F) received cow milk formula during the first days of life before the mother's breastmilk production started and was then breastfed; the other (B) was not given any formula before normal breastfeeding started. Unexpectedly, we found fewer allergic symptoms, in particular allergic skin problems, in the group fed cow milk, the difference being concentrated to children with a family history of allergic symptoms. At 5 years of age 183 of the 207 children have been reinvestigated. Mild symptoms of allergy (suspected and obvious) were found in 22% (F) and 27% (B) respectively (NS). Moderate and severe symptoms of allergy (obvious) were found in 4.2% (F) and 4.5% (B). In the subgroup with a double family history of allergic symptoms, 28% (7/25, F) and 59% (10/17, B) had symptoms of allergy (p less than 0.05). This difference was even more pronounced when laboratory tests in favour of atopic diagnosis were included, 14% (F) and 53% (B) respectively (p less than 0.05). Thus at 5 years we still find a significantly lower frequency of allergic symptoms in the subgroup fed cow milk formula early with a family history of allergic symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose polymers in diarrhoea--risk of hypernatraemia.

An infant girl with congenital heart disease was fed glucose polymers as dietary supplements. During an attack of gastroenteritis with severe diarrhoea she developed hypernatraemic dehydration, probably due to the high osmotic load of the glucose polymers. This case illustrates the importance of giving adequate amounts of free water to a child on glucose polymers, especially during excessive fluid loss.

Simultaneous production of interleukin 2, interleukin 4 and interferon-gamma by activated human blood lymphocytes.

The production of interleukin 2 (IL 2), IL 4 and interferon-gamma (IFN-gamma) by in vitro activated unselected human blood mononuclear cells was studied at a single-cell level. Individual lymphokine-synthesizing cells were identified by intracellular immunofluorescent staining using cytokine-specific monoclonal or polyclonal antibodies. Cultures from adult blood donors revealed a biphasic kinetic production pattern for IL 2 and IFN-gamma with peaks occurring 4-6 and 24-30 h after initiation of the cultures. Approximately 20%-40% of the lymphocytes produced IL 2 and IFN-gamma. In contrast, only 1%-3% of the lymphocytes synthesized IL 4 with maximal frequency after 6 h of culture. CD4+ as well as CD8+ T cells contributed to the synthesis of all three lymphokines studied. CD4+CD45R- T cells were the major producers of IL 2 and IL 4, while CD8+CD45R- T cells were the most common phenotype of IFN-gamma-synthesizing cells. By performing two-color immunofluorescence studies we observed that among IL 4-producing cells every second one made simultaneously IL 2 and every fourth one made IFN-gamma. Mononuclear cells from umbilical cord blood could be stimulated to make IL 2 to the same extent as cells from adult blood donors. No IL 4 production and a strikingly reduced frequency of IFN-gamma producers were noted in cell cultures from neonates. IL 2, IL 4 and IFN-gamma accumulated in the Golgi system, which resulted in a characteristic morphology of the staining, eliminating problems with evaluation of background signals.

Oral melphalan pharmacokinetics--relation to dose in patients with multiple myeloma.

The pharmacokinetics of melphalan have been studied after oral doses of 5, 10 and 20 mg, and 10 mg i.v. Seven patients with multiple myeloma received the drug on 4 consecutive days and the concentration of melphalan was determined by liquid chromatography. Melphalan was rapidly absorbed after p.o. administration. Absorption lag-time was less than 1 h. The median time for attaining the peak concentration was 1.12 h (97% confidence interval: 0.68-1.55), 1.21 h (0.85-1.43) and 1.08 h (0.84-1.29) after doses of 5, 10 and 20 mg. The bioavailability showed large interindividual variations, and was not significantly affected by the dose given. There was a significant decrease in bioavailability during the treatment course (P less than 0.05). Absorption of melphalan obeys first-order kinetics in the dose interval studied. The results indicate that it might be of benefit to administrate oral melphalan for fewer days than the usually used 4 day regimen, in an attempt to achieve a higher bioavailability.

Penicillin allergy--a rare paediatric condition?

A total of 298 children with a history of adverse reactions in connection with oral penicillin treatment were investigated with a radioallergosorbent test for penicillin metabolites, the skin prick test, and oral challenge with penicillin V. No severe reactions were seen. In 30 (10%) of the subjects slight to moderate skin reactions were observed on the seventh to 10th day of the challenge period. Between one to four years after the oral challenge 222 children were reinvestigated by interview. One hundred and ten had been given treatment by penicillin and 103 (94%) of these children tolerated the new treatment well and without any adverse reactions. We conclude that the term 'penicillin allergy' is often misused. Such a diagnosis should be established by clinical investigation.

Free amino acids in rat ocular tissues during postnatal development.

Amino acid changes in the retina, vitreous, lens, iris-ciliary body and cornea of the rat eye were determined during postnatal growth. The amino acid concentrations of the ocular tissues showed varying profiles at various developmental stages. These results suggest a different timetable for development of each ocular tissue or indicate a synthesis of specific proteins in the postnatal period. Adult amino acid levels appeared to be fully reached on the 30th day after birth at the latest. Quantitatively the greatest changes were observed in taurine concentrations, which increased in all five ocular tissues during maturation. GABA changes paralleled those of taurine in the retina, whereas in the other ocular tissues GABA changes were very low. The greatest decrease in glutamic acid and aspartic acid concentration during postnatal development was in the lens, where these amino acids probably are needed for the synthesis of the lenticular proteins, the alpha-, beta-, and gamma-crystallines.

Development of atopic disease after early administration of cow milk formula.

We prospectively studied the incidence of atopic disease in healthy term infants with a birth weight between -1 and -2 SD who were fed a cow milk formula during the first few days of life. A total of 216 infants were randomized to receive either early feeding with formula before normal breastfeeding was started (n = 112) or "normal feeding" with breastmilk (n = 104). Symptoms of allergy developed in 18% of the infants before 18 months of age in the formula fed group, as compared to 33% in the breastfed group (P less than 0.05). The difference was confined to the group of infants with a history of allergy in two family members. Thus, 11% of the formula-fed infants developed allergy symptoms, as compared to 61% of the control infants (P less than 0.01). Our study implies that early feeding during the first days of life with a cow milk formula, before the introduction of breastmilk, may reduce the incidence of allergy symptoms before 18 months of age in infants with a family history of allergy.