An ultralow-noise superconducting radio-frequency ion trap for frequency metrology with highly charged ions.

We present a novel ultrastable superconducting radio-frequency (RF) ion trap realized as a combination of an RF cavity and a linear Paul trap. Its RF quadrupole mode at 34.52 MHz reaches a quality factor of Q ≈ 2.3 × 105 at a temperature of 4.1 K and is used to radially confine ions in an ultralow-noise pseudopotential. This concept is expected to strongly suppress motional heating rates and related frequency shifts that limit the ultimate accuracy achieved in advanced ion traps for frequency metrology. Running with its low-vibration cryogenic cooling system, electron-beam ion trap, and deceleration beamline supplying highly charged ions (HCIs), the superconducting trap offers ideal conditions for optical frequency metrology with ionic species. We report its proof-of-principle operation as a quadrupole-mass filter with HCIs and trapping of Doppler-cooled 9Be+ Coulomb crystals.

A cryogenic radio-frequency ion trap for quantum logic spectroscopy of highly charged ions.

A cryogenic radio-frequency ion trap system designed for quantum logic spectroscopy of highly charged ions (HCI) is presented. It includes a segmented linear Paul trap, an in-vacuum imaging lens, and a helical resonator. We demonstrate ground state cooling of all three modes of motion of a single 9Be+ ion and determine their heating rates as well as excess axial micromotion. The trap shows one of the lowest levels of electric field noise published to date. We investigate the magnetic-field noise suppression in cryogenic shields made from segmented copper, the resulting magnetic field stability at the ion position and the resulting coherence time. Using this trap in conjunction with an electron beam ion trap and a deceleration beamline, we have been able to trap single highly charged Ar13+ (Ar XIV) ions concurrently with single Be+ ions, a key prerequisite for the first quantum logic spectroscopy of a HCI. This major stepping stone allows us to push highly-charged-ion spectroscopic precision from the gigahertz to the hertz level and below.

Real-world prevalence of programmed death ligand 1 expression in locally advanced or metastatic non-small-cell lung cancer: The global, multicenter EXPRESS study.

OBJECTIVES: Tumor programmed death ligand 1 (PD-L1) expression is associated with improved clinical benefit from immunotherapies targeting the PD-1 pathway. We conducted a global, multicenter, retrospective observational study to determine real-world prevalence of tumor PD-L1 expression in patients with NSCLC. MATERIALS AND METHODS: Patients ≥18 years with histologically confirmed stage IIIB/IV NSCLC and a tumor tissue block (≤5 years old) obtained before treatment were identified in 45 centers across 18 countries. Tumor samples from eligible patients were selected consecutively, when possible. PD-L1 expression was evaluated at each center using the PD-L1 IHC 22C3 pharmDx kit (Agilent, Santa Clara, CA, USA). RESULTS: Of 2617 patients who met inclusion criteria, 2368 (90%) had PD-L1 data; 530 (22%) patients had PD-L1 TPS ≥ 50%, 1232 (52%) had PD-L1 TPS ≥ 1%, and 1136 (48%) had PD-L1 TPS < 1%. The most common reason for not having PD-L1 data (n = 249) was insufficient tumor cells (<100) on the slide (n = 170 [6%]). Percentages of patients with PD-L1 TPS ≥ 50% and TPS ≥ 1%, respectively were: 22%/52% in Europe; 22%/53% in Asia Pacific; 21%/47% in the Americas, and 24%/55% in other countries. Prevalence of EGFR mutations (19%) and ALK alterations (3%) was consistent with prior reports from metastatic NSCLC studies. Among 1064 patients negative for both EGFR mutation and ALK alteration, the percentage with PD-L1 TPS ≥ 50% and TPS ≥ 1%, respectively, were 27% and 53%. CONCLUSIONS: This is the largest real-world study in advanced NSCLC to date evaluating PD-L1 tumor expression using the 22C3 pharmDx kit. Testing failure rate was low with local evaluation of PD-L1 TPS across a large number of centers. Prevalence of PD-L1 TPS ≥ 50% and TPS ≥ 1% among patients with stage IIIB/IV NSCLC was similar across geographic regions and broadly consistent with central testing results from clinical trial screening populations.

Targeted resequencing of candidate genes using selector probes.

Targeted genome enrichment is a powerful tool for making use of the massive throughput of novel DNA-sequencing instruments. We herein present a simple and scalable protocol for multiplex amplification of target regions based on the Selector technique. The updated version exhibits improved coverage and compatibility with next-generation-sequencing (NGS) library-construction procedures for shotgun sequencing with NGS platforms. To demonstrate the performance of the technique, all 501 exons from 28 genes frequently involved in cancer were enriched for and sequenced in specimens derived from cell lines and tumor biopsies. DNA from both fresh frozen and formalin-fixed paraffin-embedded biopsies were analyzed and 94% specificity and 98% coverage of the targeted region was achieved. Reproducibility between replicates was high (R(2) = 0, 98) and readily enabled detection of copy-number variations. The procedure can be carried out in <24 h and does not require any dedicated instrumentation.

TGF-ß signaling in gingival fibroblast-epithelial interaction.

The underlying mechanism and the therapeutic regimen for the transition of reversible gingivitis to irreversible periodontitis are unclear. Since transforming growth factor (TGF)-ß has been implicated in differentially regulated gene expression in gingival fibroblasts, we hypothesized that TGF-ß signaling is activated in periodontitis-affected gingiva, along with enhanced collagen degradation, that is reversed by TGF-ß inhibition. A novel three-dimensional (3D) gel-culture system consisting of primary human gingival fibroblasts (GF) and gingival epithelial (GE) cells in collagen gels was applied. GF populations from patients with severe periodontitis degraded collagen gels, which was reduced by TGF-ß-receptor kinase inhibition. Up-regulation of TGF-ß-responsive genes was evident in GF/GE co-cultures. Furthermore, the TGF-ß downstream transducer Smad3C was highly phosphorylated in periodontitis-affected gingiva and 3D cultures. These results imply that TGF-ß signaling is involved in fibroblast-epithelial cell interaction in periodontitis, and suggest that the 3D culture system is a useful in vitro model for therapeutic drug screening for periodontitis.

Complementary and alternative medicine in lung cancer patients: a neglected phenomenon?

Study on the use of complementary and alternative medicine (CAM) in lung cancer patients has been widely neglected. Therefore, we initiated a study on the use of CAM in lung cancer patients in addition to radiation treatment. Overall, 120 patients from 3 institutions were interviewed by a standardized questionnaire. Besides the tumor parameters and the use of CAM, the reason for the use, patient information of the medication, the information sources and the subjective condition of the patient. Altogether, 54% of the patients reported using CAM (66% of female patients, 52% of male patients). The most frequently used CAM measures were vitamin combinations (17%), mistletoe (15%), and selenium (12%). A total of 52% reported the wish to support the tumor treatment as a reason for using CAM and 27% had a 'better feeling' using CAM. 50% of CAM was bought by the patients themselves and 50% were prescribed by their family physicians. The use of CAM is frequent in lung cancer patients. Our results suggest that it is very important to obtain information on the CAM use of patients and, particularly in controlled clinical trials, to prospectively document it.

Cytokine profile in synovial fluid from patients with internal derangement of the temporomandibular joint: a preliminary study.

OBJECTIVES: Temporomandibular joint disorders (TMD) comprise a group of chronic painful conditions of mastication in the temporomandibular joint (TMJ). Although the association between TMD and internal derangement of the TMJ is well documented, the functional relevance is still unclear. Increased concentrations of inflammatory mediators have been identified in the synovial fluid of affected patients with TMD, suggesting an underlying degenerative or inflammatory process. The aim of this study was to generate a comprehensive cytokine expression profile in TMD. METHODS: 15 samples from patients with internal derangement of TMJ were analysed using a novel cytokine array that enables the analysis of 79 different cytokines simultaneously. RESULTS: Cytokine levels were correlated with the presence of joint effusion (JE) determined by MRI. In the majority of synovial fluid samples, angiogenin (Ang), fibroblast growth factor (FGF)-9, insulin-like growth factor-binding protein (IGFBP)-3, interleukin (IL)-1alpha, IL-1beta, IL-8, inducible protein (IP)-10, macrophage inflammatory protein (MIP)-1beta, osteoprotegerin (OPG), transforming growth factor (TGF)-beta2, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, tumour necrosis factor (TNF)-beta and vascular endothelial growth factor (VEGF) were detectable. Furthermore, the expression levels of Ang, brain-derived neurotrophic factor (BDNF), FGF-4, FGF-9, IGFBP-2, IL-8, MIP-1beta, OPG, pulmonary and activation-regulated protein (PARC), TGF-beta2, TIMP-2 and VEGF were significantly associated with the presence of JE; among these, nine cytokines (Ang, BDNF, FGF-4, FGF-9, IGFBP-2, MIP-1beta, PARC, TGF-beta2 and TIMP-2) were hitherto not described in TMD. CONCLUSIONS: This study confirmed previous reports of elevated cytokine levels in TMD. Additionally, we identified previously undescribed cytokines that were upregulated and correlated significantly with the presence of JE. We were able to identify novel cytokines that have hitherto not been described in TMD. Strategies targeting the identified cytokines may represent a novel therapy option in TMD.

Glutathione deficiency of the lower respiratory tract in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown aetiology. Increased oxidant burden and antioxidant, e.g. glutathione (GSH), deficiency in the lower respiratory tract have been thought to play a role in the progression of IPF. Sputum induction is a safe noninvasive tool to study inflammation in the respiratory tract. The aim of the present study was to evaluate the direct measurement of GSH in induced sputum supernatant. Sixteen IPF patients and 15 healthy, nonsmoking subjects underwent sputum induction. Total GSH in sputum, saliva and plasma was measured spectrophotometrically. Sputum GSH was decreased more then four-fold in IPF patients when compared to healthy subjects (mean GSH 1.4+/-0.34 microM versus 5.8+/-0.98 microM). Salivary GSH was generally low or undetectable in all subjects. Plasma GSH levels were lower in IPF patients (0.26+/-0.1 versus 0.74+/-0.16 microM). In IPF patients, there was a borderline correlation of sputum GSH levels with disease duration and lung-function impairment. These data confirm the established role of oxidant/antioxidant imbalance in the pathogenesis of idiopathic pulmonary fibrosis, and show the potential of induced sputum to directly study inflammatory processes and surrogate markers in interstitial lung diseases like idiopathic pulmonary fibrosis.

Effects of long-term supplementation with whey proteins on plasma glutathione levels of HIV-infected patients.

BACKGROUND: HIV infection is characterized by an enhanced oxidant burden and a systemic deficiency of the tripeptide glutathione (GSH), a major antioxidant. The semi-essential amino acid cysteine is the main source of the free sulfhydryl group of GSH and limits its synthesis. Whey proteins are rich in cysteine as well as in GSH precursor peptides. AIM OF THE STUDY: In order to evaluate the effects of whey supplementation on plasma GSH levels, HIV-infected patients were treated with whey proteins for a period of six months. METHODS: In a double blind clinical trial, 30 patients were randomized to a daily dose of 45 g whey proteins of either Protectamin (Fresenius Kabi, Germany) or Immunocal (Immunotec, Europe) for 2 weeks. Eighteen patients (16 male, 42 +/- 9.4 yr, 249 +/- 99 CD4+ lymphocytes/l) continued the trial with a daily dose of 45 g of Protectamin for six months. RESULTS: Pre-therapy, total plasma GSH levels (Protectamin: 1.92 +/- 0.6 microM; Immunocal: 1.99 +/- 0.9 microM) were less than normal (2.64 +/- 0.7 microM, p = 0.03). After two weeks of whey protein supplementation, plasma total GSH levels increased in the Protectamin group by 44 +/- 56% (2.79 +/- 1.1 microM, p = 0.004), while the difference in the Immunocal group did not reach significance (+24.5 +/- 59 %, 2.51 +/- 1.48 microM, p = 0.43). Consequently, all patients continuing the trial were openly switched to Protectamin. After six months, total GSH plasma levels were still significantly elevated compared to baseline (day 1: 1.95 +/- 0.8 microM vs. month 1: 2.18 +/- 0.8 microM, p = 0.19; month 3: 2.39 +/- 0.9 microM, p = 0.056; month 6: 2.47 +/- 0.8 microM, p = 0.033). Body weight, T-cell counts, and other clinical parameters did not change. The most common mild side effect was intestinal disturbance; severe adverse events did not occur. CONCLUSION: Supplementation with whey proteins persistently increased plasma glutathione levels in patients with advanced HIV-infection. The treatment was well tolerated. A larger long-term trial is clearly warranted to evaluate whether this positive influence on the glutathione metabolism translates into a more favorable course of the disease.

Sputum levels of metalloproteinase-9 and tissue inhibitor of metalloproteinase-1, and their ratio correlate with airway obstruction in lung transplant recipients: relation to tumor necrosis factor-alpha and interleukin-10.

BACKGROUND: Chronic transplant rejection is characterized by progressive narrowing of small airways caused by matrix remodeling and fibrosis. Matrix-metalloproteinases (MMPs) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), are involved in the turnover of extracellular matrix. METHODS: To clarify the contribution of MMPs and TIMPs to airway inflammation in patients after lung transplantation (LTx), we used enzyme immunoassays to measure induced sputum concentrations of MMP-9, TIMP-1, and controlling cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 of 30 LTx patients and 15 control subjects. RESULTS: Sputum concentrations of MMP-9, TIMP-1, the MMP-9:TIMP-1 ratio, and TNF-alpha were higher in LTx patients than in control subjects (p < 0.04, all comparisons). The MMP-9, MMP-9:TIMP-1, and TNF-alpha levels were also significantly higher in LTx patients with chronic rejection compared with those with stable organ function (p < 0.03, all comparisons), whereas IL-10 levels were higher in the latter group (p = 0.05). In all LTx patients, MMP-9 and the MMP-9:TIMP-1 ratio were negatively correlated with forced expiratory volume in 1 second values (rho = -0.47, p = 0.01, and rho = -0.53, p = 0.003, respectively). We found that MMP-9 positively correlated with sputum neutrophils and TNF-alpha whereas MMP-9 and TIMP-1 did not correlate with IL-10. CONCLUSIONS: These data underline the possible contribution of proteases such as MMP-9 to chronic transplant rejection, and suggest that an imbalance of MMP-9 and TIMP-1 may be involved in the pathogenesis of airway obstruction after LTx. We found that MMP-mediated inflammation seems to be controlled by TNF-alpha whereas IL-10 might elicit anti-inflammatory effects through different pathways.

c-erbB-2 expression in small-cell lung cancer is associated with poor prognosis.

Small-cell lung cancer (SCLC) carries a bad prognosis despite good initial response to chemotherapy. It is therefore important to identify molecular markers that influence survival as potential new therapeutic targets. In our study, expression of the tyrosine kinase c-erbB-2 (HER2/neu) receptor in tumor tissues of 107 consecutive newly diagnosed patients with primary SCLC was quantified using a monoclonal antibody directed against the c-terminal domain of c-erbB-2. A clear-cut positive expression of c-erbB-2 was observed in 13% of patients. Surprisingly, c-erbB-2 was an independent prognostic factor (RR = 2.16; p = 0.014) when a proportional-hazard model was adjusted to stage (limited vs. extensive disease) and performance status (WHO I-IV), the most relevant clinical parameters. Similarly, a significant association between c-erbB-2 and survival was obtained if a larger number of clinical parameters were included into the analysis, namely response to chemotherapy, TNM stage, lactate dehydrogenase (LDH), neuron-specific enolase (NSE), gender and age (p = 0.033). Interestingly, c-erbB-2 expression was more relevant for patients with advanced tumors. In the subgroup of patients with bad performance status (WHO II-IV), median survival of patients with undetectable c-erbB-2 expression was 274 days compared with only 23 days for patients with clear-cut positive c-erbB-2 immunohistochemistry (p = 0.0031; log-rank test). Similar results were obtained for patients with extensive disease (p = 0.028) and high TNM stages (T>2 or N>1 or M1; p < 0.068, all comparisons). In contrast, c-erbB-2 expression was not associated with survival in patients with limited disease (p = 0.97), low TNM stages (p > 0.56, all comparisons) and good performance status (p = 0.97). In conclusion, c-erbB-2 is expressed in more than 10% of SCLC. Expression of c-erbB-2 is an independent prognostic factor of survival. The effect of c-erbB-2 expression seems to become more important in advanced stages of the disease. Since c-erbB-2 is a therapeutical target in other types of cancer, further studies to identify the role of c-erbB-2 in SCLC are clearly warranted.

Cigarette smoking, but not sensitization to Alternaria, is associated with severe asthma in urban patients.

Hereditary susceptibility and allergen exposure have been identified as general risk factors for asthma. However, risk factors for severe asthma still remain to be identified. To further assess and quantify risk factors associated with severe asthma in adult patients apart from clinical exacerbations, 306 randomly selected subjects (mean age 40+/-17 years, 46% males) presenting to an inner city pulmonary practice between 1995 and 1996 were retrospectively investigated. Of these, 117 patients were atopic, 112 had current asthma, and 22 asthmatics had severe asthma. Risk factors associated with atopy were family history of atopy and any domestic pet ownership (OR: 3.1, 95% CI: 1.64-6.1). Asthma was generally associated with atopy (OR: 4.2, CI: 2.4-7.4) and pet ownership (OR: 2.4, CI: 1.2-4.6). Severe asthma was strongly associated with current smoking (OR: 4.8, CI: 1.3-18.3), and lung function was negatively correlated with the amount of consumed cigarettes per day (r = -0.61, p = 0.04). However, no association with sensitization to Alternaria was found in severe asthma. Cigarette smoking is an independent risk factor associated with severe asthma in urban patients, whereas sensitization to Alternaria is of less importance in these patients.

Oral supplementation with whey proteins increases plasma glutathione levels of HIV-infected patients.

HIV infection is characterized by an enhanced oxidant burden and a systemic deficiency of the tripeptide glutathione (GSH), a major antioxidant. The semi-essential amino acid cysteine is the main source of the free sulfhydryl group of GSH and limits its synthesis. Therefore, different strategies to supplement cysteine supply have been suggested to increase glutathione levels in HIV-infected individuals. The aim of this study was to evaluate the effect of oral supplementation with two different cysteine-rich whey protein formulas on plasma GSH levels and parameters of oxidative stress and immune status in HIV-infected patients. In a prospective double blind clinical trial, 30 patients (25 male, 5 female; mean age (+/- SD) 42 +/- 9.8 years) with stable HIV infection (221 +/- 102 CD4 + lymphocytes L-1) were randomized to a supplemental diet with a daily dose of 45 g whey proteins of either Protectamin (Fresenius Kabi, Bad Hamburg, Germany) or Immunocal (Immunotec, Vandreuil, Canada) for two weeks. Plasma concentrations of total, reduced and oxidized GSH, superoxide anion (O2-) release by blood mononuclear cells, plasma levels of TNF-alpha and interleukins 2 and 12 were quantified with standard methods at baseline and after therapy. Pre-therapy, plasma GSH levels (Protectamin: 1.92 +/- 0.6 microM; Immunocal: 1.98 +/- 0.9 microM) were less than normal (2.64 +/- 0.7 microM, P = 0.03). Following two weeks of oral supplementation with whey proteins, plasma GSH levels increased in the Protectamin group by 44 +/- 56% (2.79 +/- 1.2 microM, P = 0.004) while the difference in the Immunocal group did not reach significance (+ 24.5 +/- 59%, 2.51 +/- 1.48 microM, P = 0.43). Spontaneous O2- release by blood mononuclear cells was stable (20.1 +/- 14.2 vs. 22.6 +/- 16.1 nmol h-1 10-6 cells, P = 0.52) whereas PMA-induced O2- release decreased in the Protectamin group (53.7 +/- 19 vs. 39.8 +/- 18 nmol h-1 10-6 cells, P = 0.04). Plasma concentrations of TNF-alpha and interleukins 2 and 12 (P > 0.08, all comparisons) as well as routine clinical parameters remained unchanged. Therapy was well tolerated. In glutathione-deficient patients with advanced HIV-infection, short-term oral supplementation with whey proteins increases plasma glutathione levels. A long-term clinical trial is clearly warranted to see if this "biochemical efficacy" of whey proteins translates into a more favourable course of the disease.

Autoantibodies against the angiotensin receptor (AT1) in patients with hypertension.

Sera from patients with malignant essential hypertension (n = 14), malignant secondary hypertension mainly attributable to renovascular diseases (n = 12) and renovascular diseases without malignant hypertension (n = 11) and from normotensive healthy blood donors (n = 35) were studied for the presence of autoantibodies against G-protein-coupled cardiovascular receptors. Autoantibodies against the angiotensin II receptor (AT1) were detected in 14, 33, 18 and 14% of patients with malignant essential hypertension, malignant secondary hypertension, renovascular diseases and control patients, respectively. Sensitivity of the enzyme immunoassay was assessed as 5 microg/ml IgG. Patients did not show antibodies against bradykinin (B2) or angiotensin II subtype 2 (AT2) receptors. Autoantibodies affinity-purified from positive patients localized AT receptors in Chinese hamster ovary transfected cells, and displayed a positive chronotropic effect on cultured neonatal rat cardiomyocytes. These results demonstrate the existence of autoantibodies against a functional extracellular domain of human AT1 receptors in patients with malignant hypertension, and suggest that these autoantibodies might be involved in the pathogenesis of malignant hypertension.

Soot-exposed mononuclear cells increase inflammatory cytokine mRNA expression and protein secretion in cocultured bronchial epithelial cells.

BACKGROUND: Soot particles are air pollutants capable of inducing airway and lung parenchymal injury. Mononuclear and bronchial epithelial cells are central to the maintenance of homeostasis and inflammation in the airways. OBJECTIVES: The aim of this study was to evaluate the contribution of mononuclear cells to the release of inflammatory mediators by bronchial epithelial cells. METHODS: To model the in vivo situation, an in vitro system of cocultured blood monocytes and BEAS-2B cells was established in a transwell system. Blood monocytes were exposed to soot particles (FR 101) at concentrations of up to 100 microg/10(6) cells. Inflammatory cytokine mRNA and protein concentrations were quantified in BEAS-2B mono- and BEAS-2B-BM cocultures by RT-PCR and ELISA following exposure to soot for 1 and 8 h. RESULTS: No inflammatory cytokine mRNA expression was observed in unstimulated BEAS-2B cells. IL-6 and IL-8 mRNA and protein levels showed a dose-dependent elevation in FR 101-exposed blood monocytes. In addition, both IL-6 and IL-8 mRNA expression was upregulated in cocultured BEAS-2B cells while cytokine concentrations in the blood monocyte-BEAS-2B coculture medium were significantly increased. This upregulation was likely due to a synergism of two cell populations. CONCLUSIONS: Exposure to soot particles induces an autocrine stimulation of inflammatory cytokine release by blood monocytes and BEAS-2B cells. Since IL-6 and IL-8 play a major role in the pathogenesis and persistence of bronchial inflammation, these findings may serve as a partial explanation for the aggravation of asthmatic and bronchitic symptoms after exposure to soot.

Asbestos-exposed blood monocytes--deoxyribonucleic acid strand lesions in co-cultured bronchial epithelial cells.

OBJECTIVES: In lungs of asbestos-exposed persons alveolar and interstitial macrophages are able to release genotoxic substances such as reactive oxygen intermediates. It is unknown whether reactive oxygen intermediates released by macrophages are able to induce DNA (deoxyribonucleic acid) strand lesions in neighboring bronchial epithelial cells. METHODS: A co-culture (transwell) system was established which allows exposure of human blood monocytes cultured on a polycarbonate membrane within a distance of 1 mm of a monolayer of the bronchial epithelial cell line BEAS-2B. RESULTS: Exposure of blood monocytes to chrysotile B (100 microg/10(6)cells) caused an up to 2.8-fold increase in DNA strand lesions in co-cultured BEAS-2B cells measured by alkaline elution when compared with the levels of control cells after 1, 3, 24, and 48 hours. The main DNA damage thus occurred as early as within 1 hour of incubation, corresponding to the time course of the release of reactive oxygen intermediates by blood monocytes determined by chemiluminescence. The maximum release of reactive oxygen intermediates (3.2-fold increase over control values) was measured after 30 minutes of exposure of blood monocytes to chrysotile B. The addition of catalase (200 U/ml) or desferoxamine (100 microM) to the culture medium blocked almost completely the induction of DNA strand lesions in this system (maximum 85%). CONCLUSIONS: Exposure of blood monocytes to chrysotile B results in an increase in the release of reactive oxygen intermediates and induces DNA strand lesions in neighboring bronchial epithelial cells.

[Correlation of plasma glutathione and total IgE level: evidence for a regulatory role of antipxodants in vivo]. / Korrelation von Plasma-Glutathion und Gesamt-IgE-Spiegeln: Hinweise für eine regulatorische Rolle von Antioxidantien In vivo.

BACKGROUND: Atopy is characterized by increased levels of circulating immunoglobulin E (IgE). Moreover, elevated IgE levels are frequently observed in HIV-infected individuals and are of prognostic significance in these patients. Several In vitro studies have established an association of intracellular antioxidants like glutathione with IgE production by B-lymphocytes, suggesting a regulatory role of these substances in IgE synthesis. However, in vivo data consistent with these findings have not been reported. METHODS: Total IgE levels, CD4(+)-lymphocyte count and plasma glutathione were determined in non-atopic, HIV-positive individuals. RESULTS: 27 HIV-positive subjects (mean age Alter +/- SD: 43 +/- 11 years, 85% males) were studied. Mean CD4(+)-lymphocyte count was 250 +/- 136/microliter. The median serum IgE level was 85.3 U/ml (Range: 3-1298 U/ml), and the mean plasma glutathione concentration was 2.08 +/- 0.7 muMol. Plasma glutathione was significantly correlated with CD4(+)-lymphocyte count (r = 0.37; p = 0.05), and was inversely related to total IgE (r = -0.46; p = 0.01). CONCLUSIONS: Plasma glutathione and total IgE levels are negatively correlated in HIV-positive individuals. This observation supports the concept of a regulatory role of antioxidants and IgE synthesis in vivo. Further studies aiming at the possible significance of these mechanisms in atopic patients are clearly warranted.