Age-related prevalence of antibodies to infective larvae ofWuchereria bancrofti in normal individuals from a filaria-endemic region

Antibody isotypic levels (IgM, IgE and IgG subclasses) to infective larvae (L₃) ofWuchereria bancrofti were measured in 104 normal individuals from a filaria-endemic region in Orissa. The titres of antibodies were considerably higher in adults (n = 25, 25.1± 3.8 year) than in children (n = 52, 7.1 ± 2.1 year). Young children (n = 14) less than four years were seronegative to all isotypes other than IgM, the sero-conversion to which was achieved in the children (n=15) by the age of 7.5±1.2 years. The prevalence of other isotypes increased with age and reached a maximum in early adulthood (18.6 ±1.6 years), which persisted in older adults (> 30 years). However, the increase in IgG₃ prevalence with age was less marked. IgG₂ was detected only after 10 years of age. Compared to the high prevalence (100%) of IgM, IgE, IgG₁, and IgG₂, in adults. IgG₃ and IgG₄ prevalences were low, 35% and 28% respectively. IgA level to L₃ antigen was found to be extremely low even in adults. These data indicate that the prevalence of L₃ antibodies was different for different isotypes and the acquisition of antibody response essentially followed an age dependent pattern.     

Naturally occurring plasmodium-specific IgA antibody in humans from a malaria endemic area

Blood samples collected from individuals belonging to an endemic area in Uttar Pradesh, were tested for plasmodial antigen specific immunoglobulin A (IgA) by enzyme immuno assay using soluble extract ofPlasmodium falciparum from culture. Among 773 (20.18%,P < 0.0001) samples 156 sera demonstrated a detectable seropositivity for antigen specific IgA. IgA levels were higher among individuals who experienced repeated attacks of malaria compared to acute infected patients. Among seropositive individuals the IgA titers were found increased with the age. Immunoglobulin isolated from sera having high level of IgA showed growth inhibitory effect inPlasmodium falciparum in vitro. A group of sera with high IgA antibody againstPlasmodium falciparum crude antigen showed seronegativity with specific peptides. Statistically, no positive or negative correlations were observed between antigen specific IgG and IgA. However, there was a tendency towards negative correlation between IgA and IgM. Mechanisms for the parasite specific IgA production remain to be established.     

A gene‐driven recovery mechanism: Drosophila larvae increase feeding activity for post‐stress weight recovery

Recovery from weight loss after stress is important for all organisms, although the recovery mechanisms are not fully understood. We are working to clarify these mechanisms. Here, we recorded enhanced feeding activity of Drosophila melanogaster larvae from 2 to 4 h after heat stress at 35°C for 1 h. During the post‐stress period, expression levels of sweet taste gustatory receptor genes (Grs), Gr5a, Gr43a, Gr64a, and Gr64f, were elevated, whereas bitter taste Grs, Gr66a, and Gr33a, were decreased in expression and expression of a non‐typical taste receptor Gr, Gr68a, was unchanged. Similar upregulation of Gr5a and downregulation of Gr66a was recorded after cold stress at 4°C. Expression levels of tropomyosin and ATP synthase ß subunit were significantly increased in larval mouth parts around 3 to 5 h after the heat stress. We infer that up‐regulation of post‐stress larval feeding activity, and weight recovery, is mediated by increasing capacity for mouth part muscular movements and changes in taste sensing physiology. We propose that Drosophila larvae, and likely insects generally, express an efficient mechanism to recover from weight loss during post‐stress periods.     

The Effect of Enriched Milk with Selenium and Vitamin E on Growth Rate, Hematology, Some Blood Biochemical Factors, and Immunoglobulins of Newborn Goat Kids

Thirty male and female (n?=?15 for each one) Markhoz newborn goat kids (aged 7?±?3 days) were distributed in a randomized block design in a 2?×?2?+?1 factorial arrangement: two levels of sodium selenite as a source of selenium (0.2 or 0.3 ppm Se), two levels of α-tocopherol acetate as a source of vitamin E (150 or 200 IU Vit E), and one control treatment with six repetitions per treatment (each replicate included three male and three female kids). Animals were fed daily by Se-Vit E-enriched milk (Se-Vit E treatments) or non-enriched milk (control treatment). Growth rate, hematology, and serum biological parameters were measured. The levels of serum albumin (P?<?0.01), serum globulin (P?<?0.05), total serum protein levels (P?<?0.01), erythrocyte counts (RBC) (P?<?0.001), hemoglobin (P?<?0.001), hematocrit (P?<?0.001), leukocyte counts (WBC) (P?<?0.001), IgA (P?<?0.05), IgG (P?<?0.01), and IgM (P?<?0.01) significantly differed among treatments, while no significant differences were observed for calcium, lymphocyte, neutrophil average daily gain and body weight among treatments. Kids feeding by enriched milk with 0.3 ppm Se and 200 IU Vit E had significantly higher serum total protein, globulin, RBC, IgA, IgG, and IgM compared to control and those fed by enriched milk to 0.2 ppm Se and 200 IU Vit E had significantly higher WBC counts.     

Causal analysis of the variability of IgA, IgG, and IgM immunoglobulin levels

The interindividual variability of IgA, IgG, and IgM immunoglobulin levels was studied using path analysis in a northeastern Brazilian sample (nuclear families) to determine the genetic and/or environmental causes of their variation. The path analysis model decomposes the phenotype into genetic causes (autosomal and X-chromosome-linked genes) and environmental causes. A significant familial aggregation, mainly resulting from autosomal components, was detected for the 3 immunoglobulin levels. The values of genetic heritability were h2 = 0.410 +/- 0.030 for IgA, h2 = 0.617 +/- 0.020 for IgG, and h2 = 0.540 +/- 0.023 for IgM, and the values for environmental-cultural heritability were c2 = 0.085 +/- 0.034 for IgA, c2 = 0.084 +/- 0.027 for IgG, and c2 = 0.023 + 0.023 for IgM. Our results did not show a heritable component resulting from X-chromosome-linked genes on IgM levels, as suggested by some studies (Wood et al. 1969; Grundbacher 1972; Purtilo and Sullivan 1979). Some additional results were that (1) age and IgA concentration were positively correlated, with IgA level increasing gradually from childhood to adulthood (p < 0.001); (2) sex and the age X sex interaction act on IgG concentration (p < 0.01); (3) age and IgM concentration are correlated (with children presenting lower levels than adults, especially in males, p < 0.01); and (4) a significant association exists between sex and IgM level (with females presenting higher levels than males, p < 0.001).     

Nasopharyngeal carcinoma patients from Norway show elevated Epstein-Barr virus IgA and IgG antibodies prior to diagnosis

BackgroundIgA antibodies against few Epstein-Barr virus (EBV) proteins are established serological markers for nasopharyngeal carcinoma (NPC). We recently validated a novel, comprehensive EBV marker panel and showed that IgA, but also IgG antibodies against multiple EBV proteins are highly sensitive and specific for EBV-positive NPC at diagnosis. However, data about these novel biomarkers as prospective markers for NPC are sparse.MethodsThis study included 30 incident NPC cases and 60 matched controls from the Norwegian Janus Serum Bank. For 21 NPCs, molecular EBV and human papillomavirus (HPV) status were assessed by EBER-ISH and HPV DNA/RNA testing by PCR, respectively. IgA and IgG serum antibodies against 17 EBV antigens were analyzed in prediagnostic sera of cases (median lead time 14 years) and controls using multiplex serology. Sensitivities were calculated using receiver operating characteristic analysis pre-specified to yield 90% specificity in the control group. From 10 cases, serial samples were available.ResultsQuantitative EBV antibody levels were significantly elevated among all cases (p < 0.05) for three IgA and six IgG antibodies. The highest sensitivities for defining 12 EBER-ISH-positive NPCs were observed for BGLF2 IgA (67%) and BGLF2 IgG (83%). Increased IgA and IgG antibody levels between the first and last draw before diagnosis were observed for EBER-ISH positive, but not for EBER-ISH negative NPCs. Among 21 molecularly analyzed NPCs, 4 EBER-ISH negative NPCs showed concomitant positivity to HPV type-specific DNA and RNA; 3 NPCs were HPV16 and 1 NPC was HPV18 positive.ConclusionBoth, EBV IgA and IgG antibody levels are significantly elevated many years before diagnosis of EBV-positive NPCs in Norway, an NPC low-incidence region. This study provides insights into one of the largest available prospective sample collections of NPCs in a non-endemic country.     

Effects of different doses of free 𝛂-linolenic acid infused to the duodenum on the immune function of lactating dairy cows

This study investigated the effect of a duodenal infusion of a C18:3 free fatty acid on the immune function of lactating dairy cows. Four primiparous Chinese Holstein cows fitted with duodenal cannulas received 0, 100, 200, 300, and 400 g/d of α-linolenic acid (LNA) in a two-treatment crossover design. Blood was collected and serum IgA, IgG, IgM, prostaglandin E₂ (PGE₂) and Th1/Th2 cytokines were determined. Results showed that increasing the supply of LNA to the small intestine of dairy cows linearly increased serum IgG and quadratically enhanced interferon-γ (p < 0.05), whereas the concentrations of PGE₂ declined linearly (p < 0.05) and those of interleukin (IL)-4 tended to decrease (p = 0.08). No difference was observed in serum IgA, IgM or other cytokines, such as IL-2, IL-6 and IL-10. This study demonstrated that in dairy cows, a post-ruminal infusion of high doses of LNA has immunomodulatory effects, possibly associated with a predisposition to a Th1-type response.     

Molecular phylogenetic study of several eelpout fishes (Perciformes,Zoarcoidei) from Far Eastern seas on the basis of the nucleotide sequences of the mitochondrial cytochrome oxidase 1 gene (<Emphasis Type="Italic">Co-1</Emphasis>)

A total of 95 nucleotide sequences of a Co-1 gene fragment of approximately 650 bp were analyzed for fishes of the orders Perciformes and Scorpaeniformes (outgroup). Gene trees based on four algorithms (BA, NJ, MP, and ML) were similar in topology of solved branches. An emphasis was placed on the species and generic levels, but a significant phylogenetic signal was obtained for higher taxonomic ranks as well. For instance, a monophyletic origin was confirmed for the family Zoarcidae and the subfamily Opisthocentrinae (Stichaeidae). The proportion of different nucleotides in the sequences compared (p-distances) significantly increased with increasing taxonomic rank. The p-distances were estimated for four hierarchic levels and were (1) 0.15 ± 0.06% for the within-species hierarchic level, (2) 6.33 ± 0.37% for the within-genus level, (3) 11.83 ± 0.06% for the within-family level, and (4) 15.22 ± 0.05% for the within-order level. The difference in the Co-1 gene fragments between levels (1) and (2) allows almost errorless species identification on the basis of this kind of a molecular bar code.     

Seasonal variation in steroid hormones and blood parameters in cage-farmed European sea bass (Dicentrarchus labrax L.)

For a period of 1 year, some blood parameters were evaluated on a monthly basis in a population of adult European sea bass (Dicentrarchus labrax L.) intensively reared in floating marine cages (Ionian Sea, Mediterranean). From April (13 months old) to July (16 months old) males (35–50%) and sexually indeterminate individuals were collected. From August to March (24 months old) only males were sampled. During this period the percentage of spermiated males was highest (100%) from November (20 months old) to January (22 months old). Plasma testosterone in males was inversely related to sunlight (h month^?1) and was elevated between October and January, when males first achieved sexual maturity. Testosterone showed the highest value (0.49 ± 0.02 ng ml^?1) in January and the lowest (0.09 ± 0.02 ng ml^?1) in March. Haematocrit, red blood cell counts and haemoglobin concentration were elevated from November to March, being inversely related to sunlight. The two latter parameters were also inversely related to daily food intake. Haematocrit, red blood cell counts and haemoglobin concentration were highest in December [53 ± 1%, (5.36 ± 0.06) × 10⁶ mm^?3, 10.08 ± 0.14 g 100 ml^?1, respectively] and lowest in June [35 ± 1%, (3.33 ± 0.05) × 10⁶ mm^?3, 6.47 ± 0.13 g 100 ml^?1, respectively]. White blood cell counts were not correlated with sea water temperature, sunlight or daily food intake. They were highest in February [(8.45 ± 0.20) × 10⁴ mm^?3] and lowest in April [(6.07 ± 0.14) × 10⁴ mm^?3]. Total plasma protein concentration (4.88 ± 0.11–5.93 ± 0.10 g 100 ml^?1) and mean cell volume (93.3 ± 0.9–105.5 ± 1.8 μm³) showed small fluctuations throughout the year. Sexual maturity appears to be a major factor that significantly affects haemopoiesis of D. labrax. This study contributes to the evaluation of normal levels of some blood parameters in European sea bass, which are helpful for the assessment of physiological status and health of this species.     

Effects of CO2 and light on tree phytochemistry and insect performance

Direct and interactive effects of CO₂ and light on tree phytochemistry and insect fitness parameters were examined through experimental manipulations of plant growth conditions and performance of insect bioassays. Three species of deciduous trees (quaking aspen, Populus tremuloides; paper birch, Betula papyrifera; sugar maple, Acer saccharum) were grown under ambient (387±8 μL/L) and elevated (696±2 μL/L) levels of atmospheric CO₂, with low and high light availability (375 and 855 μmol×m^?2×s^?1 at solar noon). Effects on the population and individual performance of a generalist phytophagous insect, the white‐marked tussock moth (Orgyia leucostigma) were evaluated. Caterpillars were reared on experimental trees for the duration of the larval stage, and complementary short‐term (fourth instar) feeding trials were conducted with insects fed detached leaves.
Phytochemical analyses demonstrated strong effects of both CO₂ and light on all foliar nutritional variables (water, starch and nitrogen). For all species, enriched CO₂ decreased water content and increased starch content, especially under high light conditions. High CO₂ availability reduced levels of foliar nitrogen, but effects were species specific and most pronounced for high light aspen and birch. Analyses of secondary plant compounds revealed that levels of phenolic glycosides (salicortin and tremulacin) in aspen and condensed tannins in birch and maple were positively influenced by levels of both CO₂ and light. In contrast, levels of condensed tannins in aspen were primarily affected by light, whereas levels of ellagitannins and gallotannins in maple responded to light and CO₂, respectively.
The long‐term bioassays showed strong treatment effects on survival, development time, and pupal mass. In general, CO₂ effects were pronounced in high light and decreased along the gradient aspen birch maple. For larvae reared on high light aspen, enriched CO₂ resulted in 62% fewer survivors, with increased development time, and reduced pupal mass. For maple‐fed insects, elevated CO₂ levels had negative effects on survival and pupal mass in low light. For birch, the only negative CO₂ effects were observed in high light, where female larvae showed prolonged development. Fourth instar feeding trials demonstrated that low food conversion efficiency reduced insect performance. Elevated levels of CO₂ significantly reduced total consumption, especially by insects on high light aspen and low light maple.
This research demonstrates that effects of CO₂ on phytochemistry and insect performance can be strongly light‐dependent, and that plant responses to these two environmental variables differ among species. Overall, increased CO₂ availability appeared to increase the defensive capacity of early‐successional species primarily under high light conditions, and of late‐successional species under low light conditions. Due to the interactive effects of tree species, light, CO₂, and herbivory, community composition of forests may change in the future.     

The effect of dietary methionine levels on fattening performance and selected blood and tissue parameters of turkeys

A total of 490 eight-week-old female Hybrid Converter turkeys (body weight 4.11 ± 0.03 kg) were divided into 5 groups with 7 replicates of 14 birds each. For 8 weeks, basal diets were supplemented with methionine (Met) at following levels (weeks 9–12/weeks 13–16 of age): Group 1 – 0.34/0.29%, Group 2 – 0.39/0.34%, Groups 3 and 4 – 0.45/0.38% and 0.51/0.41%, respectively, Group 5 – 0.58/0.47%. Only in the first feeding phase the body weight gain (BWG) was affected by Met levels with the significantly highest BWG in Group 3. No treatment effects were found for feed conversion ratio, carcass yield, carcass composition and meat colour. The blood superoxide dismutase activity was significantly highest in Groups 2 and 3. The concentrations of reduced glutathione in the liver were linearly increased (p = 0.018), whereas the ratio of reduced glutathione to oxidised glutathione was highest in Group 3 (quadratic contrast, p = 0.004). It can be concluded that turkeys from Group 3 (Met levels age depending 15% and 10% above recommendations by NRC) were characterised by a well-balanced physiological response. Attention should be paid to the immune response of birds to higher dietary Met levels: plasma IgA concentrations decreased, whereas IL-6 and TNF-α levels increased in turkeys fed diets with the highest Met content.     

Prior Exercise Increases Dietary Oleate,but Not Palmitate Oxidation

Objective: Higher levels of physical activity have been associated with body weight maintenance, but previous work in our laboratory suggests that this is not purely related to energy balance. We hypothesize that this may be related to the partitioning of dietary fat between oxidation and storage. Research Methods and Procedures: Healthy women (age 24 ± 1 years, BMI = 21.2 ± 0.4 kg/m²) were recruited to participate in rest (n = 10) or exercise sessions of light (n = 11), moderate (n = 10), and heavy (n = 7) exercise. All exercises (1250 kJ above rest) were performed on a stationary cycle inside of a whole‐body calorimeter. [1‐¹³C]oleate and [d₃₁]palmitate were given in a liquid meal 30 minutes post‐exercise. An additional study was done with identical exercise sessions, but with administration of an oral dose of [1‐¹³C]acetate and [d₃]acetate 30 minutes post‐exercise to determine label sequestration. Results: Cumulative oxidation of [1‐¹³C]oleate was significantly greater after light (45 ± 3%), moderate (54 ± 4%), and heavy (51 ± 4%) exercise than that with rest (33 ± 3%) (p = 0.0008). Cumulative oxidation of [d₃₁]palmitate did not differ among trials (12 ± 2%, 14 ± 1%, 17 ± 2%, and 14 ± 2% for rest, light, moderate, and heavy, respectively; p = 0.30). Discussion: Exercise standardized for energy expenditure increases monounsaturated fat oxidation more than saturated fat oxidation and that the increase occurs regardless of intensity. Recommendations for physical activity for the purposes of weight control may be specific for dietary fat composition.     

Phylogenetic and taxonomic analysis of flatfish species (Teleostei,Pleuronectiformes) inferred from the primary nucleotide sequence of cytochrome oxidase 1 gene (<Emphasis Type="Italic">Co-1</Emphasis>)

Seventeen nucleotide sequences of Co-1 gene from 13 Pleuronectiformes species and 2 Perciformes species served as the outgroup were examined. For divergence comparison, the initial stage involved calculation of pairwise p-distances for all investigated sequences. This allowed to evaluate the nucleotide diversity on four phylogenetically different levels: (1) intraspecific, (2) intrageneric, (3) intrafamilial, and (4) intraordinal. The values of p-distances for the Co-1 gene for the four mentioned categories were (1) 0.93 ± 0.73%, (2) 11.72 ± 1.86%, (3) 12.10 ± 1.10%, and (4) 20.20 ± 0.22%, respectively. An increase in the level of genetic divergence along with an enhancement in taxon rank was previously reported for different species, which might be explained by prevalence of geographic speciation model in nature. Phylogenetic trees were constructed using four approaches: maximum parsimony, Bayesian, maximum likelihood, and neighbor-joining. These trees demonstrated similar results confirming the monophyletic origin of the families studied. The examined representatives of the flatfish species and genera were shown to be sufficiently divergent genetically.     

Effects of soybean glycinin on performance and immune function in early weaned pigs

Glycinin, a major storage protein in soybean, has been identified as an important food allergen. The present study was conducted to investigate the effects of soybean glycinin on the local and systemic immune responses using a swine model specific for glycinin allergy. Performance, peripheral blood lymphocyte proliferation and CD4⁺ and CD8⁺  subsets in the plasma of naive and sensitised piglets were determined. In addition, the concentrations of IgA, IgG, IgM, interleukin-4 and interleukin-6 in the jejunum mucosa were measured. Our results showed that dietary supplementation of glycinin reduced piglet performance (p < 0.05), while increasing lymphocyte proliferation and CD4⁺/CD8⁺  ratio (p < 0.01). Intestinal mucosal immune responses to glycinin were enhanced with high levels of IgA (p < 0.01) as well as interleukin-4 and interleukin-6 in the jejunum mucosa in glycinin-treated piglets compared with the control (p < 0.01). There were no differences due to treatment in the densities of IgG and IgM. In conclusion, it was found that glycinin stimulated local and systemic immune responses in allergic piglets and had negative effects on piglet performance. The severity of the immune reactions depends on the dose of glycinin with higher doses causing more severe symptoms.     

The first report on immunoglobulins A,E, G and M levels in cystic fibrosis patients in Saudi Arabia

BackgroundPrevious reports have shown that pulmonary and systemic hypergamma-globulinemia in CF patients is a reflection of chronic pulmonary infection. Infection with Pseudomonas aeruginosa is known to have major prognostic significance in patients CF. This study aims to identify the incidence of immunoglobulins (especially: IgG, and IgE) in a cohort of CF patients.MethodsA total of 297 patients recruited all over the country’s region for this study were a as part of the CF registry data from 1st January 1984 to 1st June 2016. All patients had their immunoglobulin levels measured by enzyme link immunosorbent assay (ELISA) in 3 stages, at presentation and two follow-ups.ResultsOf the 297 patients recruited, 139 (46.8%) were males while 158 (53.2%) were females. IgA and IgM levels were found not to have risen above the previously reported levels in healthy individuals in all stages. On the contrary, IgE level increased from 209.51 ± 32.30 KU/L to 303.58 ± 37.11 KU/L from baseline to stage 3 while IgG level rose from 12.26 ± 0.43 mg/mL to 17.17 ± 1.68 mg/mL for baseline and stage 3 respectively all above previously reported levels in healthy individuals.ConclusionThis study establishes a potential for the use of IgE and IgG in disease diagnosis as well as the prognostic implications. However, further study is needed to identify the role of infection or medications in relation to the rise of both IgE and IgG with advancement of age and progression of disease severity which may inherently confound the observed results.     

Intestinal endotoxin as a trigger of type 1 diabetes mellitus

The blood serum level of intestinal flora endotoxin was studied in 45 children and adolescents aged 3–17 years with type 1 diabetes mellitus. In all the patients the endotoxin levels 2.89 ± 0.33 EU/ml) were significantly elevated compared to the control group (0.4 ± 0.03 EU/ml). A higher level of endotoxin at the disease onset (3.93 ± 0.79 EU/ml) compared to that in children afflicted with diabetes for more than two years (2.37 ± 0.27 EU/ml) gives evidence of the involvement of endotoxin in the initiation of the disease.     

Intrastriatal Infusion of (±)-S-Nitroso-N-Acetylpenicillamine Releases Vesicular Dopamine via an Ionotropic Glutamate Receptor-Mediated Mechanism: An In Vivo Microdialysis Study in Chloral Hydrate-Anesthetized Rats

Abstract: The existence of both nitric oxide synthase (NOS) immunoreactive interneurons and amino acid neurotransmitter-mediated nitric oxide (NO) release in the striatum suggests a role for NO in modulating striatal function. To explore the potential interaction between NO and dopaminergic neurotransmission, the NO-releasing agent (±)-S-nitroso-N-acetylpenicillamine (SNAP) was administered locally into the anterior medial striatum of chloral hydrate-anesthetized rats. SNAP, at 0.5, 1, and 2 mM concentrations, elevated striatal extracellular (EC) dopamine (DA) to 200 ± 42, 472 ± 120, and 2,084 ± 496%, respectively, above baseline levels. Perfusion with (±)-penicillamine (PEN, 1 mM), the non-NO-containing carrier component of SNAP, was ineffective, indicating that PEN is not responsible for SNAP-mediated DA release. Additional microdialysis experiments suggest SNAP-mediated DA release is not due to NO-induced neurotoxicity or blockade of the DA transporter. The DA-releasing effect of SNAP was attenuated under calcium-free conditions and abolished in rats pretreated with reserpine (5 mg/kg), implicating a calcium-sensitive vesicular-dependent release process. To determine the mechanism of SNAP-mediated DA release, the guanylyl cyclase (GC) inhibitor LY 83583 (100 µM) was administered 100 min before and during the SNAP pulse. LY 83583 elevated EC DA levels approximately fivefold and potentiated the DA-releasing effect of SNAP to 2,598 ± 551% above basal DA levels. Similar pretreatments with both the noncompetitive N-methyl-d -aspartate (NMDA) antagonist MK-801 (10 µM) and the competitive NMDA-receptor antagonist (±)-3-(carboxypiperazin-4-yl)propyl-1-phosphonic acid [(±)-CPP, 100 µM] blocked SNAP-mediated DA release. SNAP-mediated DA release was also significantly blunted by pretreatment and coperfusion with MgSO₄ (10 mM) and 6,7-dinitroquinoxaline-2,3-dione (DNQX, 10 µM) but not (+)-2-amino-3-phosphonopropionic acid (AP-3, 10 µM). These results suggest that NO releases DA via a calcium-sensitive vesicular-dependent process that is independent of GC activation. In addition, NMDA and kainate/(±)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated mechanisms are implicated in NO-induced DA release.     

Anti-dsDNA Antibody Isotypes in Systemic Lupus Erythematosus: IgA in Addition to IgG Anti-dsDNA Help to Identify Glomerulonephritis and Active Disease

Objectives

To evaluate the role of serum IgG, IgM and IgA anti-dsDNA antibody isotypes in the diagnosis of systemic lupus erythematosus (SLE), and their association with clinical features and disease activity, in a large cohort of SLE patients.

Methods

Sera of 200 SLE patients (mean age 34±10.3 years; 26 male and 174 female; median duration of disease 115 months, range 7–378), and of 206 controls, including 19 Sjögren''s syndrome, 27 rheumatoid arthritis, 26 psoriatic arthritis, 15 idiopathic inflammatory myopathies (IIM), 13 systemic sclerosis, 49 infectious diseases and 57 healthy subjects, were tested for anti-dsDNA IgG, IgM and IgA isotypes.

Results

Selecting a cutoff corresponding to 95% specificity, the sensitivity of IgG, IgM and IgA anti-dsDNA antibodies in SLE was 55%, 30% and 49%, respectively; 12.5%, 1% and 7.5% of SLE patients had positive IgG, IgM or IgA isotype alone, respectively. SLE patients with glomerulonephritis showed higher levels of IgA anti-dsDNA (p = 0.0002), anti-dsDNA IgG/IgM (p = 0.001) and IgA/IgM (p<0.0001) ratios than patients without renal disease. No significant associations have been found between anti-dsDNA isotypes and other clinical features. IgA anti-dsDNA (p = 0.01) (but not IgG or IgM) and IgG/IgM ratio (p = 0.005) were significantly higher in patients with more active disease (ECLAM score >4).

Conclusions

The detection of IgA anti-dsDNA autoantibodies seems to improve our ability to diagnose SLE and to define lupus nephritis phenotype and active disease. By contrast, IgM anti-dsDNA antibodies might be protective for renal involvement. These data support the hypothesis that anti-dsDNA antibody class clustering may help to refine SLE diagnosis and prognosis.     

Characterizing Intrinsic Bioremediation in a Petroleum Hydrocarbon-Contaminated Aquifer by Combined Chemical,Isotopic, and Biological Analyses

Chemical, isotopic, and biological parameters were evaluated over a 1-year period to characterize microbial processes associated with intrinsic bioremediation in a petroleum hydrocarbon-contaminated aquifer located in Studen, Switzerland. Chemical parameters measured included oxidants such as O₂, NO₃ ^?, and SO₄ ^2?, reduced species such as Fe²⁺ and CH₄, and dissolved inorganic carbon (DIC). Stable carbon isotope analyses of DIC were used to differentiate between different processes that contribute to DIC production. Microbial populations were identified by sequence analysis of archaeal 16S rDNA and in situ hybridization using a general DNA binding dye (DAPI) and specific probes targeting the domain Archaea (Arch915) and Bacteria (Eub338), as well as the species Methanosaeta concilii (Rotcl1) and Methanospirillum sp. (Rotcl2). Groundwater exhibited reduced conditions and elevated concentrations of DIC within the contaminated zone. Spatially distinct values of δ¹³C ranging from ?16.5l%c to ?4.44%o were found, indicating the presence of different ongoing microbial processes. Detected microbial populations (% of DAPI-stained cells) within the contaminated zone belonged to Archaea (9±2% to 31±13%) and Bacteria (13±3% to 32±13%). In wells with methanogenic activity, Methanosaeta concilii accounted for up to 26% of all DAPI-detected microorganisms. These results demonstrate that this novel combination of chemical, isotopic, and biological analysis provides valuable insights that can be used for the characterization of microbial processes in contaminated aquifers.     

Pathogenic Role of a Proliferation-Inducing Ligand (APRIL) in Murine IgA Nephropathy

A proliferation-inducing ligand (APRIL) is a member of the tumor necrosis factor (TNF) superfamily. Despite advances in clinical and genetic studies, the details of the pathological roles of APRIL in IgA nephropathy (IgAN) remain to be fully defined. The present study aimed to further assess the pathological role of APRIL using a mouse model of IgAN. Mice with IgAN designated “grouped ddY” (gddY) were intraperitoneally administered an anti-APRIL monoclonal antibody (anti-APRIL Ab) or control IgG (Control Ab) twice each week for 2 weeks starting during the early stage of IgAN (6–7 weeks of age). Urinary albumin, serum IgA, and glomerular IgA deposition were evaluated. We further assessed the inflammatory responses during treatment by measuring the levels of the chemokine fractalkine (FKN) and its receptor CX3CR1 as well as the level of peripheral blood monocytosis. Anti-APRIL Ab treatment significantly decreased albuminuria and tissue damage combined with decreases in serum IgA levels and deposition of glomerular IgA. In contrast, the abundance of IgA⁺/B220⁺ or CD138⁺/B220⁺ B cells in the spleen and bone marrow, respectively, was unchanged. Treating gddY mice with anti-April Ab reduced the overexpression of FKN/CX3CR1 in the kidney and the increase in the population of circulating Gr1⁻/CD115⁺ monocytes. The size of the population of Gr1⁻/CD115⁺ monocytes correlated with renal FKN and urinary albumin levels. Moreover, mice treated with anti-APRIL Ab exhibited reduced progression of IgAN, serum IgA levels, and glomerular IgA deposition as well as an attenuated inflammatory process mediated by FKN-associated activation of monocytes. To the best of our knowledge, this is the first study to implicate the APRIL signal transduction pathway in the pathogenesis of nephrogenic IgA production. Moreover, our findings identify APRIL as a potential target of therapy.