Search PubMed⌕ Search

Biomedical subjects

M Ott

Publications and source records attributed to M Ott.

At least 37 records · Page 2Linked to original sources

Effects of the serine/threonine kinase SGK1 on the epithelial Na(+) channel (ENaC) and CFTR: implications for cystic fibrosis.

Cystic fibrosis (CF) is characterized by impaired Cl(-) secretion and increased Na(+) reabsorption in several tissues including respiratory epithelium. Many CFTR mutations have been identified over the past years. However, only a poor correlation between the genotype and lung phenotype was found suggesting additional factors influencing the phenotype and course of the disease. The serine/threonine kinase SGK1 has recently been shown to stimulate the activity of the epithelial Na(+) channel ENaC. A variety of stimuli such as aldosterone, cell shrinkage, insulin or TGF-beta1 stimulate transcription and activate the SGK1 kinase. Here we further examined the effects of SGK1 on ENaC and CFTR which have mutual interactions and we analyzed sgk1 mRNA abundance in lung tissue from CF patients. Coexpression of CFTR and h-SGK1 in Xenopus oocytes increased ENaC currents as previously described. In addition CFTR mediated currents were also stimulated. h-SGK1 accelerated the expression of the amiloride sensitive Na(+)- current in Xenopus oocytes paralleled by increased ENaC-protein abundance in the oocyte membrane, an effect which was reversed by a h-SGK1(K127R) mutation lacking the ATP-binding site. The cation selectivity or Na(+) affinity were not affected. However, coexpression of h-SGK1 with ENaC altered the sensitivity of the Na(+)-channel to the inhibitors amiloride and triamterene. The inhibitory effect of CFTR expression on ENaC current was not affected by coexpression of h-SGK1 in Xenopus oocytes. Lung tissue from CF patients strongly expressed the serine/threonine kinase h-sgk1 which was not the case for non-CF lung tissue. Loss of CFTR function itself in a CF lung epithelial cell line did not increase SGK1 expression. In summary, enhanced expression of h-SGK1 in epithelial cells of CF-lung tissue may be a novel pathophysiological factor contributing to increased Na(+) channel activity and thus to increased Na(+) transport in CF.

1-Methyl-3-isobutylxanthine↗

[Mites and their allergens: identification and extermination methods].

Mite allergens are the main allergens in indoor environment. Using different means of assessing exposure to house dust mites (Acarex-test, major allergen (Der p 1 + Der f 1, Der p 2 + Der f 2), content measured by ELISA) has allowed better identification of mite reservoirs and allergens in patients' homes. House dust mite control measures are based on the knowledge of factors contributing to mite development, especially indoor relative humidity. Mite allergen avoidance strategies include 3 different methods: avoidance of mite producing allergens, elimination of mite reservoirs, especially textile reservoirs, dwellings designed so as to inhibit mite proliferation. Only controlled trials can estimate patients' compliance with proposed avoidance measures. Avoidance protocols should be adjusted to each individual by medical indoor environment counselors in order to optimize mite allergen reduction.

Allergens↗

Adjuvant therapy of melanoma with interferon-alpha-2b is associated with mania and bipolar syndromes.

BACKGROUND: The use of a high dose regimen of interferon-alpha-2b (IFN) has recently been demonstrated to benefit patients with resected high risk melanoma. The incidence of melanoma is rising rapidly, and the use of this regimen is becoming increasingly common. IFN has been associated with numerous psychiatric side effects. METHODS: The authors describe four melanoma patients treated with adjuvant IFN who developed a manic-depressive syndrome or mood instability with therapy, and they review the literature on mania and the mixed affective syndromes associated with IFN. RESULTS: The authors suggest that IFN may induce a mixed affective instability, and that patients risk developing hypomania or mania as IFN doses fluctuate or as IFN-induced depression is treated with antidepressants alone. Mania is particularly associated with dose reductions or pauses in IFN treatment. The risk of mood fluctuation continues after treatment with IFN stops, and patients should be monitored for 6 months following completion of therapy. Gabapentin appeared effective as monotherapy for acute mania, as an antianxiety agent, as a hypnotic, and as a mood stabilizer in these individual cases. CONCLUSIONS: Mania and mood instability can occur in patients being treated with IFN therapy for melanoma. In this study, gabapentin was an effective mood-stabilizing agent for these patients.

Acetates↗

Emerging therapies in hepatology: liver-directed gene transfer and hepatocyte transplantation.

Gene transfer and epithelial cell transplantation technologies play an important role in the development of new therapeutic concepts for liver diseases. Although liver organ transplantation has revolutionized the treatment of a wide spectrum of acute and chronic liver diseases, gene- and cell-based therapies are emerging at an astonishing pace, because they promise to be less invasive, less costly and at least as effective as currently established therapy protocols. Experimental gene therapy models have been developed for a wide spectrum of liver diseases, including hereditary liver disorders, malignant liver disease and viral hepatitis. Hepatocyte transplantation (HcTx) is being explored as treatment of severe chronic and acute liver failure as well as for hereditary liver diseases. Most of these procedures and techniques are still experimental or have been applied to a small number of patients only. Rigorous clinical evaluation will finally demonstrate the usefulness of each new procedure in the daily clinical care of patients with liver disease. In this review, we have attempted to provide an introduction and survey of the topics of gene therapy and HcTx with specific examples of laboratory and clinical achievements highlighting potential applications in liver diseases.

Animals↗

Convergence of specialised behaviour, eye movements and visual optics in the sandlance (Teleostei) and the chameleon (Reptilia)

Chameleons have a number of unusual, highly specialised visual features, including telescopic visual optics with a reduced lens power, wide separation of the eye's nodal point from the axis of rotation, a deep-pit fovea, rapid pre-calculated strikes for prey based on monocular depth judgements (including focus), and a complex pattern of partially independent alternating eye movements. The same set of features has been acquired independently by a teleost, the sandlance Limnichthyes fasciatus. Despite its underwater lifestyle, this fish displays visual behaviour and rapid strikes for prey that are remarkably similar to those of the chameleon [1]. In a direct comparison of the two species, we have revealed other, previously unsuspected, similarities, such as corneal accommodation, which was unknown in teleosts, as well as bringing together, for the first time, data collected from both species. The sandlance is the only teleost, among thousands studied, that has corneal refraction, corneal accommodation and reduced lens power, as well as sharing the other specialised optical features seen in chameleons. The independent eye movement pattern in the sandlance is also unusual and similar to that of the chameleon. The selection pressures that have produced this remarkable example of convergence may relate to common visual constraints in the life styles of these two phylogenetically disparate species.

Animals↗

Paclitaxel shows cytotoxic activity in human hepatocellular carcinoma cell lines.

Paclitaxel stabilizes microtubules with inhibition of mitotic spindle formation and has been found effective in several solid cancers. To test whether paclitaxel could be cytotoxic in human HCC cell lines, we used established HuH-7 and HepG2 cell lines. Changes in cell number, DNA synthesis rates and cell viability were determined. We tested whether paclitaxel-treated cells underwent apoptosis, microtubular reorganization, and cell cycle restriction. Studies also examined whether chemosensitization with verapamil enhanced the antitumor activity of paclitaxel. The cell viability was impaired at greater than 0.01 microM paclitaxel concentrations (LD50, 0.8 microM), with flow cytometry indicating accumulation of cells in G2/M, and immunostaining showing polymerized microtubules with characteristic banding patterns. This G2/M restriction was further characterized by flow cytometry, which revealed cyclin A and cdc2 kinase accumulation in paclitaxel-treated cells. Exposure to paclitaxel decreased [3H]thymidine incorporation into DNA in cells at 24 h but this significantly increased at 72 h, most likely due to DNA repair mechanisms related to cell cycle restriction. The cell death was via both apoptotic and non-apoptotic mechanisms. Finally, co-administration of the chemosensitizer verapamil in doses as little as 1 microM increased the antitumor efficacy of paclitaxel by up to five-fold and changed the LD50 of paclitaxel to 0.1 microM. The findings indicate that paclitaxel is cytotoxic to cultured hepatocellular carcinoma cells. Clinical studies of paclitaxel in patients with hepatocellular carcinoma may help determine additional therapies.

Adolescent↗

Differentiation-specific regulation of transgene expression in a diploid epithelial cell line derived from the normal F344 rat liver.

To establish the differentiation potential of progenitor cells, non-parenchymal epithelial cells from the F344 rat liver (FNRL cells) were studied. These cells reacted with the OV-6 antibody marker of oval cells, but were negative for hepatocyte markers (albumin, transferrin, glycogen, glucose-6-phosphatase, H4 antigen), biliary markers (gamma glutamyl transpeptidase, cytokeratin-19), and alpha-fetoprotein, although exposure to sodium butyrate induced nascent albumin and alpha-fetoprotein mRNA transcription. When stably transduced, FNRL cells expressed a retroviral promotor-driven lacZ reporter in vitro, similar to transgene expression in hepatocyte-derived HepG2 cells. However, lacZ expression in FNRL cells was rapidly extinguished in intact animals, whereas the reporter remained active in HepG2 cells. Transplanted FNRL cells showed copious glucose-6-phosphatase expression; however, the cell differentiation programme remained incomplete, despite two-thirds partial hepatectomy, D-galactosamine treatment or bile duct ligation. Interestingly, lacZ expression resumed in cultures of FNRL cells explanted from recipients. Moreover, lacZ expression was down-regulated by gamma-interferon in FNRL cells, without affecting lacZ activity in HepG2 cells. The data indicate that although subpopulations of oval cells may not fully differentiate into mature hepatocytes, these cells might serve critical functions, such as glucose utilization, and help survival after liver injury. Also, introduced genes may be regulated in progenitor cells at multiple levels, including by interactions between regulatory sequences, differentiation-specific cellular factors, and extracellular signals; in vivo studies are thus especially important for analysing gene regulation in progenitor cells.

Animals↗

Contamination of human milk in Middle Hesse, Germany--a cross-sectional study on the changing levels of chlorinated pesticides, PCB congeners and recent levels of nitro musks.

Human milk samples from women in Middle Hesse, Germany were chemically analyzed for contamination levels of alpha-, beta- and gamma-HCH, HCB, p,p'-DDE and p,p'-DDT as well as the PCB-congeners no. 28, 31, 49, 52, 101, 118, 138, 153, 156, 170 and 180. Changes in concentrations of these compounds in human milk over an extended time period were studied by comparing samples from 1984/85, 1990/91 and 1995. In addition, concentrations of the nitro-aromatic compounds musk xylene and musk ketone were determined in the 1995 samples. The study showed statistically highly significant (p<0.001) reductions in levels of beta- and gamma-HCH, HCB, p,p'-DDE and p,p'-DDT, in human milk from 1995 compared to samples from 1984/85. A weakly significant reduction (p<0.05) of alpha-HCH was also observed. For low-chlorinated PCB congeners, on the other hand, a highly significant increase of PCB no. 28 was detected and concentrations of congeners no. 31, 49 and 52 remained unchanged. Concentrations of the high-chlorinated congeners no. 101, 138, 153 and 180 dropped (highly significant). A highly significant reduction of PCB no. 118 and 156 occurred between 1990/91 and 1995, but a highly significant increase was found for no. 170. Lower levels of hydrocarbon contamination of human milk samples from 1995 than were found in samples from 1984/85 and 1990/91 can be seen to result partially from voluntary reductions, but primarily reflect restrictive environmental legislation in the Federal Republic of Germany. Mean concentrations of musk xylene and musk ketone in samples from 1995 were 41 microg/kg and 10 microg/kg milk fat, respectively.

Adult↗

Rapid clearance of syngeneic transplanted hepatocytes following transduction with E-1-deleted adenovirus indicates early host immune responses and offers novel ways for studying viral vector, target cell and host interactions.

To distinguish between transduced cell clearance and transgene regulation following adenoviral gene transfer, we infected F344 rat hepatocytes with an E-1-deleted adenovirus (Ad beta gal) and studied cell survival in the liver of dipeptidyl peptidase IV-deficient (DPPIV-) F344 rats. Transplanted cells were localized with histochemical staining for DPPIV and transgene expression localized with staining for beta-galactosidase (lacZ). The transgene was expressed in 90-100% hepatocytes without impairment in cell viability in vitro, although transplanted cells were cleared mostly within 1 day by infiltrates containing activated macrophages, CD4+ or CD8+ lymphocytes, and phagocytes. When Ad beta gal-transduced hepatocytes were transplanted repeatedly at 14-day intervals, transplanted cells were cleared rapidly each time. LacZ expression following Ad beta gal administration to intact animals was associated with apoptosis and unscheduled DNA synthesis in the liver. To determine whether adenoviral antigen expression activated consequential MHC-restricted liver injury, we transplanted Ad beta gal-hepatocytes followed subsequently by transplantation of nontransduced hepatocytes. Transplanted cells expressing Ad beta gal were rapidly cleared as before, whereas nontransduced hepatocytes engrafted with progressive liver repopulation. The findings indicated that adenovirally transduced cells are cleared early in the host liver. Use of ex vivo strategies will facilitate analysis of modified adenoviral vectors in the context of immunoregulatory, cellular and viral mechanisms.

Adenoviridae↗

Regulation of hepatitis B virus expression in progenitor and differentiated cell types: evidence for negative transcriptional control in nonpermissive cells.

Mechanisms regulating cell type-specific gene expression are not completely understood. We utilized hepatitis B virus (HBV) enhancer I and preS1 promoter sequences, which exhibit cell type specificity, to analyze transcriptional control in pluripotential murine embryonic stem (ES) cells, bipotential HBC-3 progenitor liver cells, mature hepatocytes, and fibroblasts. In transient transfection assays, HBV sequences were most active in primary hepatocytes, followed by HBC-3 and ES cells, and became inactive in fibroblasts. Cotransfections with HNF-3 or C/EBP plasmids increased expression of HBV sequences in hepatocytes and HBC-3 cells. However, increased HBV expression was not observed in ES cells and HBV remained inactive in fibroblasts, suggesting different transcriptional controls, which was compatible with alterations in the abundance of endogenous transcription factors. Analysis in somatic hybrid cells created from NIH 3T3 fibroblasts and Hepa1-6 mouse hepatocytes with expression of albumin and selected hepatic transcription factors showed that HBV sequences were expressed weakly but without increased expression following transfection of HNF-1, HNF-3, and C/EBP plasmids. These findings indicated that repression of HBV in nonpermissive cells involved inactivation of transcription factor activity. Expression of HBV in stem cells is relevant for mechanisms concerning viral persistence and oncogenesis, as well as analysis of hepatocytic differentiation in progenitor cells.

3T3 Cells↗

Inhibition of internal entry site (IRES)-mediated translation by a small yeast RNA: a novel strategy to block hepatitis C virus protein synthesis.

The observation that poliovirus mRNA is not translated in the yeast Saccharomyces cerevisiae has led to the discovery of a small RNA (60 nt, called IRNA, inhibitor RNA) which was later shown to specifically inhibit internal ribosome entry site (IRES)-mediated translation of naturally uncapped mRNAs. Translation of cellular capped mRNAs was not significantly inhibited by IRNA. IRNA also specifically inhibited hepatitis C virus (HCV) IRES-mediated translation in vitro and in vivo. A hepatoma cell line constitutively expressing IRNA was refractory to infection by a chimeric poliovirus (PV/HCV) in which PV IRES is replaced by HCV-IRES. In contrast, a PV/EMCV chimeric virus containing the EMCV IRES was not significantly inhibited in the IRNA-hepatoma cell line compared to the control hepatoma cells. UV-crosslinking studies showed that the IRNA binds a number of cellular proteins that appear to be important for IRES-mediated translation. Interaction of these proteins with the viral IRES elements is believed to be important in recruiting ribosomes to the 5( UTR of viral RNAs. The binding of the purified La autoantigen to the HCV IRES element was efficiently and specifically competed by IRNA. These results provide a basis for development of novel drugs effective against HCV infection.

Animals↗

Fractionation of rat hepatocyte subpopulations with varying metabolic potential, proliferative capacity, and retroviral gene transfer efficiency.

The liver contains hepatocytes with varying ploidy and gene expression. To isolate cells on the basis of ploidy for analyzing mechanisms concerning cell proliferation and differentiation, we used Percoll gradients to separate F344 rat hepatocyte subpopulations. Specific fractions were enriched in polyploid (H2 fraction) or diploid (H3 and H4 fractions) hepatocytes containing glycogen and glucose-6-phosphatase. H4 cells were relatively smaller with greater nuclear/cytoplasmic ratios, less complex cytoplasm, and higher serum albumin or ceruloplasmin biosynthetic rates. H2 fraction cells were larger with lesser nuclear/cytoplasmic ratio, more complex cytoplasm, and more cytochrome P450 activity. Phenotypic marking showed that H4 cells originated in zone one and H2 cells in zones two or three of the liver lobule. H4 cells showed much greater mitogenic responsiveness to human hepatocyte growth factor. Retroviral gene transfer, which requires both viral receptors and cellular DNA synthesis, was significantly more efficient in H4 cells. The findings indicated that small diploid and large polyploid hepatocytes show unique biological differences. The ability to isolate hepatocytes of varying maturity is relevant for mechanisms concerning liver growth control and hepatic gene expression.

Animals↗

Simultaneous up-regulation of viral receptor expression and DNA synthesis is required for increasing efficiency of retroviral hepatic gene transfer.

To understand the relative contribution of viral receptor expression and cell proliferation in retroviral gene transfer, we created human hepatocyte-derived HuH-7.MCAT-1 cell lines. These cells constitutively express the murine ecotropic retroviral receptor MCAT-1 without changes in morphology or proliferation states. The MCAT-1 receptor is also a cationic amino acid transporter, and the HuH-7.MCAT-1.7 cells showed increased Vmax of uptake and steady-state accumulation of the cationic amino acids L-arginine and L-lysine. In HuH-7.MCAT-1 cells, L-arginine uptake was significantly up-regulated by norepinephrine and dexamethasone, and hepatocyte growth factor also increased L-arginine uptake along with cellular DNA synthesis. Gene transfer was also markedly increased in HuH-7. MCAT-1.7 cells incubated with an ecotropic LacZ retrovirus, and this further increased with hormones and hepatocyte growth factor. To define whether viral receptor up-regulation by itself increased gene transfer, cell cycling was inhibited by a recombinant adenovirus expressing the Mad transcription factor (AdMad), which is a dominant-negative c-Myc regulator. This restricted cells in G0/G1, without attenuating MCAT-1 activity, as shown by flow cytometry and L-arginine uptake analysis, respectively. When asynchronously cycling HuH-7.MCAT-1.7 cells were first infected with the AdMad virus and then exposed to the ecotropic LacZ virus, gene transfer was virtually abolished. The data indicate that while up-regulation of viral receptors can greatly enhance retrovirally mediated gene transfer, DNA synthesis remains an absolute requirement for hepatic gene therapy with this approach.

Amino Acid Transport Systems, Basic↗

Superinduction of IL-8 in T cells by HIV-1 Tat protein is mediated through NF-kappaB factors.

Elevated levels of circulating IL-8, a potent chemotactic factor for granulocytes and T lymphocytes, are found in HIV-infected individuals. The HIV-1 transactivator protein Tat increased IL-8 secretion in T cell lines following CD3- and CD28-mediated costimulation. Full-length Tat (Tat101) enhanced IL-8 transcription through up-regulated transcription factor binding to the CD28-responsive element (CD28RE) in the IL-8 promoter. Expression of the Tat splice variant Tat72 (72 amino acids) also enhanced IL-8 production following T cell stimulation via a different, most likely post-transcriptional, mechanism. The CD28RE in the IL-8 promoter was characterized as a low-affinity NF-kappaB binding site recognized by the transcription factors p50 (NF-kappaB1), p65 (RelA) and c-rel. Transcription factor binding to "classical" NF-kappaB sites in the HIV-1, the human IL-2, and lymphotoxin promoters, recognized by p50 and p65 following CD3+28-mediated costimulation, was unaffected by Tat101 as was binding to the AP-1 motif in the IL-8 promoter. These experiments identify the CD28RE in the IL-8 promoter as a c-rel recognition site and a Tat101-responsive element. The effect of Tat101 on CD28REs in the IL-8 promoter and the subsequent up-regulation of IL-8 secretion is likely to contribute to the immune dysregulation observed during HIV-1 infection.

CD28 Antigens↗

Oral tolerization to adenoviral proteins permits repeated adenovirus-mediated gene therapy in rats with pre-existing immunity to adenoviruses.

Exposure to wild-type adenoviruses is common in humans and results in immune response against adenoviruses. The pre-existing antibodies and a strong secondary humoral and cellular immune response would interfere with gene transfer using recombinant adenoviral vectors. To test whether the secondary immune response can be abrogated by oral tolerization to adenoviral antigens, we immunized bilirubin-UDP-glucuronosyltransferase (BUGT)-deficient jaundiced Gunn rats with a recombinant adenovirus (5 x 10(9) pfu/rat) expressing the human UDP-glucouronosyltransferase (BUGT1) gene (Ad-hBUGT). Transgene expression was shown by reduction of mean serum bilirubin levels from 7.0 mg/dL to 2.3 mg/dL in 14 days, which then increased gradually to pretreatment levels in 6 weeks. All recipients developed antibodies (1:2[10]) and cytotoxic lymphocytes against the adenovirus. For oral tolerization, we administered to the immunized rats protein extracts of a recombinant adenovirus type 5 (1-1.5 mg/day) via duodenostomy tubes 10 to 40 days after the initial virus injection; control rats received bovine serum albumin. In rats fed adenoviral proteins and the BSA-fed controls, the antibody titers decreased to 1:2(7) and 1:2(9), respectively, in 70 days. Lymphocytes from the tolerized rats expressed TGF-beta1 upon exposure to antigen-presenting cells primed with adenoviral antigens, whereas IFN-gamma expression was undetectable. In contrast, lymphocytes from the BSA-treated control rats expressed IFN-gamma but not transforming growth factor beta1 (TGF-beta1). Seventy days after the first injection in the orally tolerized rats, but not in the controls, a second Ad-hBUGT injection caused human BUGT1 expression again, reducing serum bilirubin levels to those observed after the first injection. In the tolerized rats, serum antibody titers and anti-adenoviral cytotoxic lymphocyte activities continued to decline despite the second injection, whereas the antibody levels were boosted in the non-tolerized group. This results show that by preventing the secondary booster response, oral tolerization permits repeated adenovirus-directed gene transfer despite the presence of a residual antibody titer from a previous adenoviral exposure.

Adenoviridae↗

[3D and color Doppler ultrasound evaluation of cystic space-occupying lesion near the head of the pancreas].

AIM: Differential diagnosis of cystic lesions in the abdomen may be very difficult. We present the clinical manifestation and the diagnostic steps of a rare case of an aneurysm of the gastroduodenal artery mimicking a cystic lesion. We also discuss the imaging methods we used to verify the diagnosis such as colour Doppler sonography and 3D-sonography. METHOD AND PATIENT: A 42-year old woman with chronic pancreatitis was admitted to our hospital after an extended diagnostic program (sonography, computed tomography and laparoscopy) with the diagnosis of a pancreatic pseudocyst with vascular erosion. Using conventional sonography we found a cystic lesion of 5 x 5 cm diameter with parietal deposits between pancreas and coeliac trunk. After colour Doppler sonography we found an arterial jet in the cystic tumor; initially the source of the jet seemed to be the hepatic artery. We referred the patient to our department of radiology with the diagnosis of hepatic artery aneurysm. The aneurysm was confirmed by the angiography and was embolised with coils in the same session. However, the source of the aneurysm was not the hepatic, but the gastroduodenal artery. By postangiographical 3D-sonography we could clearly reconstruct the relation of the aneurysm to the gastroduodenal artery. CONCLUSION: Colour Doppler sonography should be the first imaging tool for clarifying cystic lesions in the abdomen. 3D-sonography is a reliable and useful method to identify visceral vessels of the abdomen. Nowadays the "gold standard" angiography should preferably be used as a therapeutic procedure.

Adult↗

Effects of various vacuum cleaners on the airborne content of major cat allergen (Fel d 1).

BACKGROUND: It has been shown that a vacuum cleaner (VC) can increase airborne cat allergen levels. This study aimed to compare the degree of leakage of airborne Fel d 1 levels among five different VCs, both under laboratory conditions and in an apartment with cats. METHODS: Three of the VCs were marketed as antiallergic: a HEPA filter VC (VC A), a water impingement and HEPA filter VC (VC B), and a foam fabric filter VC (VC C). The other two were standard VCs: VC D and VC E. VCs were tested in a 20 m3, airtight, experimental room and in a 53 m3 living room in an apartment with three cats. Air was sampled with a glass-fiber filter and an impinger at 20 l/min for 30 min before, during, and after vacuuming. Airborne Fel d 1 was measured with a two-site monoclonal ELISA assay. RESULTS: In the experimental room, no airborne Fel d 1 level was measured before using the VCs. After introducing a dust sample containing Fel d 1 in the VCs, we found that VCs A, B, and E did not provoke any increase in airborne Fel d 1. In contrast, VCs C and D significantly increased airborne Fel d 1 levels (GM: 4.9 and 5.3 ng/m3, respectively). In the apartment, all VCs induced an increase in airborne Fel d 1, which was carried by particles greater than 5 microm. However, VCs C and D provoked significantly greater increases in airborne Fel d 1 than VCs A, B, and E (P=0.0001). CONCLUSIONS: Our results suggest that: 1) The two VCs with leakage in the experimental room had greater leakages in the apartment. 2) In the apartment with cats, all VCs provoked increases in airborne Fel d 1, primarily carried by large particles. 3) Given the increased marketing of "antiallergic" VCs, further studies are needed to standardize methods for testing airborne allergen leakage by VCs.

Air Pollutants↗

Soluble HLA class I and class II antigens in patients with multiple sclerosis.

Soluble HLA class I (sHLA-I) and soluble HLA class II (sHLA-II) antigen levels during different stages of disease were investigated in paired serum and cerebrospinal fluid (CSF) samples from 37 patients with multiple sclerosis (MS) using ELISA and Western blot analysis. Soluble HLA-II antigens in the serum of untreated patients with the relapsing-remitting type of MS (RRMS) were found to be significantly elevated in acute relapse as compared to values obtained from patients under steroid treatment, in remission or healthy controls. No significant differences in circulating sHLA-I levels could be detected. In contrast, a trend towards increased intrathecal production of sHLA-I molecules in the CSF was observed in untreated RRMS patients in acute relapse, whereas the levels of soluble HLA-II antigens in the CSF were below the detection limit of the ELISA method. Our observations underline the presence of systemic immune activation in MS patients, as reflected in elevated serum sHLA-II antigen levels, and reveal a dichotomy between sHLA class I and II antigen production in the peripheral blood versus CSF in acute MS. Serial measurements of sHLA-II antigen levels might represent a non-invasive method to assess disease activity in MS patients.

Enzyme-Linked Immunosorbent Assay↗