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C Hauser

Publications and source records attributed to C Hauser.

At least 37 records · Page 2Linked to original sources
PubMed2001

Influence of occupational exposure to latex on the prevalence of sensitization and allergy to latex in a Swiss hospital.

BACKGROUND: Replacement of powdered latex gloves has been recommended in order to prevent the development of latex allergy in health care workers. The conclusion that occupational exposure to latex gloves represents a risk factor for latex allergy is mainly based on studies without exposure controls. Atopy is also thought to be a risk factor for the development of latex allergy. OBJECTIVE: To determine the prevalence of atopy, sensitization to latex, and symptoms following latex exposure in professionally exposed and nonexposed hospital personnel by means of a cross-sectional study. METHODS: Six hundred randomly sampled individuals working in medicine and surgery departments and in surgery theaters and 300 sex- and age-matched individuals classified as administrative personnel were selected from the employee data base of the Geneva University Hospital. A questionnaire about exposure to latex and symptoms following this exposure was sent to all individuals. Skin prick test reactions and serum IgE to latex as well as standard environmental allergens were determined in both groups. RESULTS: Respiratory and skin (local) symptoms but not objective tests of latex sensitization (positive skin prick test and specific IgE to latex) were significantly associated with occupational exposure to latex (p < 0.001). Only among atopics subjects was 15 years or more of occupational exposure associated with a significantly higher prevalence of local symptoms than among those who were exposed from 1 to 9 years (odds ratio: 3.2; 95% confidence interval: 1.6-6.5). Atopy was significantly associated with sensitization to latex (odds ratio: 10.3; 95% confidence interval: 4.0-26.6) but not with local symptoms. Tests of latex sensitization were both frequently positive, less frequently negative, resulting in low kappa values. CONCLUSION: These results support the current preventive health care recommendation to replace powdered latex gloves. In atopics, increasing years of occupational exposure increase the risk of developing latex allergy. In contrast to questionnaires about local symptoms, skin prick tests and specific serum IgE to latex are of limited value in epidemiologic studies of latex allergy.

Adult↗
PubMed2001

Oral carrageenan induces antigen-dependent oral tolerance: prevention of anaphylaxis and induction of lymphocyte anergy in a murine model of food allergy.

Immunosuppressive effects of carrageenan, a high-molecular-weight polysaccharide, on antibody and T cell responses have been previously demonstrated. However, its effect on anaphylaxis is unknown. Our objectives were to test carrageenan-mediated oral tolerance induction in young mice subsequently sensitized to a common cow's milk antigen. C3H/HeJ mice were fed or not lambda-carrageenan (0.5 g/L) and/or 0.01 mg/mL beta-lactoglobulin (BLG) for 5 d before oral sensitization with BLG and cholera toxin. Subsequently, the mice were challenged with BLG and symptom scores of anaphylaxis were recorded. Mesenteric lymph node cells, spleen cells, Peyer's patches cells, intraepithelial lymphocytes, and lamina propria lymphocytes were isolated and stimulated in vitro with BLG, IL-2, or left unstimulated. BLG-specific IgG, IgG(1), and IgG(2a) antibodies were measured. Pretreatment with carrageenan and BLG, but not pretreatment with either carrageenan or BLG alone or omission of pretreatment, diminished significantly the number of anaphylactic mice after BLG challenge (6.3 % versus 53 % in mice without pretreatment, p = 0.006). Mesenteric lymph nodes and spleen cells from pretreated mice proliferated less in presence of BLG or IL-2 than cells from sensitized control mice. Antigen-specific antibody production and passive cutaneous anaphylaxis was not suppressed by carrageenan and BLG pretreatment. In conclusion, carrageenan administered to young mice in conjunction with low doses of allergen before sensitization efficiently prevents anaphylaxis.

Administration, Oral↗
PubMed2000

Dendritic cells containing apoptotic melanoma cells prime human CD8+ T cells for efficient tumor cell lysis.

Dendritic cells (DCs) phagocytose apoptotic influenza-infected monocytes and cross-present influenza antigen to CD8+ T cells, generating a specific CTL response. We investigated whether apoptotic melanoma cells, presented by this mechanism, can lead to CTL responses to tumor-associated antigens and melanoma cells. Apoptotic HLA-A2- MEL-397 melanoma cells were internalized by HLA-A2+ immature monocyte-derived DCs but failed to induce maturation of DCs. When exposed to interleukin 6, interleukin 1beta, tumor necrosis factor alpha, and prostaglandin E2, DCs containing apoptotic MEL-397 cell material matured normally [cross-presenting DCs (cp-DCs)]. Autologous CD8+ CTL lines generated with cp-DCs produced tumor necrosis factor when stimulated with HLA-A2-binding immunodominant peptides from MelanA/MART1 and MAGE-3 (expressed by MEL-397 cells) but not tyrosinase (absent in MEL-397). T2 target cells loaded with the respective peptides were lysed by these cell lines, although to a lesser extent than by CTL lines generated in the presence of mature DCs and peptides from melanoma-associated h antigens. In contrast, lines generated with cp-DCs lysed HLA-A2+ MEL-526 melanoma cells or allogenic HLA-A2+ cp-DCs efficiently, whereas the CTL generated with DCs and peptides had little lytic activity. Mature DCs containing apoptotic tumor cells may thus represent an alternative approach for the therapy of malignant tumors.

Antigen Presentation↗
PubMed2000

Substrate binding is a prerequisite for stabilisation of mouse thymidine kinase in proliferating fibroblasts.

Thymidine kinase (TK) expression in mammalian cells is strictly growth regulated, with high levels of the enzyme present in proliferating cells and low levels in resting cells. We have shown that mouse TK expressed from a constitutive promoter is still subject to this regulation. The drastic decline in TK enzyme levels in resting cells is largely due to a pronounced reduction in the half-life of the protein. Deletion of the 30 C-terminal amino acid residues from TK abrogates growth regulation, rendering the enzyme very stable. Moreover, the substrate thymidine was sufficient to stabilise the labile TK protein in quiescent cells. Here, we report that the ability of TK to bind substrates is essential for both growth-dependent regulation and stabilisation by the substrate. By mutation or elimination of the binding sites for either of the two substrates, ATP and thymidine, we expressed TK proteins lacking enzymatic activity which abolished growth-regulated expression in both cases. Mutant TK proteins impaired in substrate binding were subject to rapid degradation in exponentially growing cells and thymidine was no longer sufficient to inhibit this rapid decay. A C-terminal truncation known to stabilise the TK wild-type protein in resting cells did not affect the rapid turnover of enzymatically inactive TK proteins. Proteasome inhibitors also failed to stabilise these substrate-binding mutants. By cross-linking experiments, we show that TK proteins with mutated substrate-binding sites exist only as monomers, whereas active TK enzyme forms dimers and tetramers. Our data indicate that, In addition to the C terminus intact substrate-binding sites are required for growth-dependent regulation of TK protein stability.

Adenosine Triphosphate↗
PubMed2000

CD8(+) T cells secreting type 2 lymphokines are defective in protection against viral infection.

Effector T cells secreting type 1 and/or type 2 lymphokines (Tc1, Tc0, Tc2) were generated in vitro from CD8(+) T cells of mice with a transgenic TCR recognizing lymphocytic choriomeningitis virus (LCMV) glycoprotein to compare their effector function in vitro and in vivo. Tc1, Tc2, and Tc0 showed similar Fas- and perforin-mediated cytotoxicity in vitro. Upon adoptive transfer, Tc2 and Tc0 effectors were less efficient than Tc1 at controlling LCMV or recombinant vaccinia virus expressing the LCMV glycoprotein in vivo. Tc2 and Tc0 had decreased surface VLA-4 density and deficient activation-induced LFA-1/ICAM-1-dependent homotypic adhesion in vitro. Therefore, the reduced antiviral activity in vivo of Tc2 and Tc0 compared with Tc1 is not due to reduced cytotoxic activity or IFN-gamma secretion but may be explained by defective homing to the target organ due to decreased expression and/or lower activity of adhesion molecules.

Adoptive Transfer↗
PubMed2000

Low-frequency molecular dynamics studied by spin-lock field cycling imaging.

Spin-lock adiabatic field cycling imaging (SLOAFI) relaxometry was shown to be a useful technique for obtaining a fast study of spin-lattice relaxation dispersion in the rotating frame. The aim of the present article is to describe some technical aspects of the experiment in more detail, while showing simple examples that can be compared with laboratory frame relaxation. We also present here a general discussion of the equations for an off-resonance experiment used to analyze low-frequency molecular dynamics.

Humans↗
PubMed2000

Poxvirus as a vector to transduce human dendritic cells for immunotherapy: abortive infection but reduced APC function.

Dendritic cells (DC) are potent antigen-presenting cells (APC). Ongoing preclinical and clinical studies exploit this capacity for the immunotherapy of tumors. We tested vaccinia virus (VV) as a vector to transduce human DC. Immature and mature DC were prepared from blood monocytes and infected with (1) recombinant VV expressing GFP to analyze infection rates, virus replication in DC and the effect of infection on DC phenotype and (2) recombinant VV expressing beta-galactosidase (betaGAL) under the control of viral early, intermediate and late promoters to analyze the poxvirusdriven gene expression. While the infection rate in DC was comparable to a permissive fibroblast cell line, viral betaGAL gene expression was limited to early promoters. Genes under the control of virus late promoters were not expressed by VV in DC, indicating an abortive infection. VV infection selectively reduced the surface expression of the costimulatory molecule CD80 and the DC maturation marker CD83 on mature DC while other surface molecules including CD86 and MHC remained unchanged. In line with this finding, there was a pronounced reduction in the capacity of VV-infected DC to stimulate allogeneic or autologous T cells in mixed lymphocyte reactions. Furthermore, VV infection inhibited the maturation of immature DC after exposure to proinflammatory cytokines. These results indicate that VV-derived vectors may have complex effects on their target cells. In the case of DC used for immunotherapy, this may be detrimental to their function as potent APC and particularly their capacity to activate T helper cells.

Antigen Presentation↗
PubMed2000

Recombinant humanized monoclonal antibody against CD18 (rhuMAb CD18) in traumatic hemorrhagic shock: results of a phase II clinical trial. Traumatic Shock Group.

BACKGROUND: Activated neutrophils have been shown to play a pivotal role in resuscitation injury after traumatic hemorrhagic shock. Blocking the adhesion of neutrophils with a recombinant humanized monoclonal antibody against CD18 (rhuMAb CD18) may reduce resuscitation injury but increase the risk of infection. This was a dose-finding phase II study to determine safety, pharmacokinetics, pharmacodynamics, and clinical outcome parameters for additional studies. METHODS: This was a prospective, placebo-controlled, randomized (3:1), double-blind phase II trial enrolling 116 blunt and penetrating trauma patients from 14 trauma centers over a 9-month period. Patients with hypotension (blood pressure < or =90 mm Hg) from hemorrhagic shock were given a single intravenous dose of rhuMAb CD18 or placebo. The three doses tested were 0.5, 1, and 2 mg/kg. The drug was administered within 4 hours of the hypotensive episode and no later than 6 hours from time of injury. Exclusion criteria included head injury resulting in Glasgow Coma Scale score less than 8 or a history of cardiopulmonary resuscitation in the trauma center. An independent Drug Safety and Monitoring Review Board periodically reviewed unblinded data for safety issues and to give approval for dose escalation. RESULTS: Minor and major infection rates in rhuMAb CD18 groups were comparable to placebo. There was no evidence of antibody formation against rhuMAb CD18. Linear PK was observed within the dose range studied. Duration of neutrophil binding was dose-dependent, with 2 mg/kg resulting in greater than 90% neutrophil CD18 receptor saturation for approximately 48 hours. The mortality was 6.7% (2 of 30) in the placebo group, 4.8% (1 of 21) in the 0.5-mg/kg group, 8.5% (4 of 47) in the 1-mg/kg group, and 0% (0 of 18) in the 2-mg/kg group. The study was not powered for efficacy, and none of the efficacy variables demonstrated statistical significance. Favorable trends were seen in the 2-mg/kg group as compared with placebo in median intensive care unit length of stay (5 vs. 9 days) and median time on ventilator (34 vs. 72 hours). CONCLUSIONS: A single 2-mg/kg dose of rhuMAb CD18 maintains greater than 90% saturation of neutrophil CD18 receptors for approximately 48 hours in patients with traumatic hemorrhagic shock undergoing resuscitation. There was no trend toward increased infection. A larger trial is needed to demonstrate the clinical efficacy of rhuMAb CD18, perhaps using more reliable endpoints.

Adult↗
PubMed2000

Chromosomal composition of aneuploid clones with different DNA contents in head and neck squamous cell carcinomas as determined by combined flow cytometry and fluorescence in situ hybridization.

Studies with DNA flow cytometry (FCM) have shown that DNA contents of aneuploid tumour clones vary in a wide range. The aim of this study was to analyse whether homologous chromosomal changes exist despite the individual differences that may be of general relevance for the development of gross aneuploidy in squamous cell carcinomas of the head and neck. Fluorescence in situ hybridization (FISH) with 13 centromere-specific DNA probes was applied to 3 diploid and 11 aneuploid tumours with DNA indices ranging between 0.8 and 2.2. Disomic and monosomic cell populations were prevalent findings in DNA-diploid tumours. Polysomies were common in aneuploid tumours. Different degrees of aneusomy for identical chromosomes were recurrent features in aneuploid tumours. FISH signal heterogeneity was identified for all chromosomes. The mean number of aneusomic cell populations identified for DNA-aneuploid tumours ranged between 1.6 for chromosome 17 and 3.1 for chromosome 3. Inconsistencies between FISH and FCM data may indicate that centromere-specific DNA probes identify gains and losses of marker DNA due to complex karyotypic rearrangements rather than absolute changes in chromosome numbers. Overall, there was no evidence of the critical involvement of particular chromosomes in the development of different DNA contents.

Aneuploidy↗
PubMed1999

Protective immunity from naive CD8+ T cells activated in vitro with MHC class I binding immunogenic peptides and IL-2 in the absence of specialized APCs.

Ag-specific CTL can protect against tumors and some viral infections and may be useful for adoptive immunotherapy. Here, we show that purified CD8+ T cells from naive C57BL/6 mice can be primed in vitro with different immunogenic peptides, which bind to MHC class I gene products, and IL-2 to exhibit specific and MHC-restricted effector function in vitro and in vivo protection against lymphocytic choriomeningitis virus infection and B16.F10 melanoma lung metastases. Limiting dilution assays in the absence of feeder cells with highly purified CD8+ T cells from two transgenic mice strains, each expressing a different MHC class I-restricted TCR, indicated that only peptide and IL-2, but not TCR- cells, were required for the growth of naive CD8+ T cells. These alternative minimal requirements for the activation and expansion of specific CD8+ T lymphocytes, without the need for professional APC, may be exploited for adoptive immunotherapy.

Adoptive Transfer↗
PubMed1999

p300/cAMP-responsive element-binding protein interactions with ets-1 and ets-2 in the transcriptional activation of the human stromelysin promoter.

In this paper we show that transcription factors Ets-1 and Ets-2 recruit transcription adapter proteins p300 and CBP (cAMP-responsive element-binding protein) during the transcriptional activation of the human stromelysin promoter, which contains palindromic Ets-binding sites. Ets-2 and p300/CBP exist as a complex in vivo. Two regions of p300/CBP between amino acids (a.a.) 328 and 596 and a. a. 1678 and 2370 independently can interact with Ets-1 and Ets-2 in vitro and in vivo. Both these regions of p300/CBP bind to the transactivation domain of Ets-2, whereas the C-terminal region binds only to the DNA binding domain of Ets-2. The N- and the C-terminal regions of CBP (a.a. 1-1097 and 1678-2442, respectively) which lack histone acetylation activity independently are capable of coactivating Ets-2. Other Ets family transcription factors failed to cooperate with p300/CBP in stimulating the stromelysin promoter. The LXXLL sequence, reported to be important in receptor-coactivator interactions, does not appear to play a role in the interaction of Ets-2 with p300/CBP. Previous studies have shown that the stimulation of transcriptional activation activity of Ets-2 requires phosphorylation of threonine 72 by the Ras/mitogen-activated protein kinase signaling pathway. We show that mutation of this site does not affect its capacity to bind to and to cooperate with p300/CBP.

Binding Sites↗
PubMed1999

Long-term culture of human CD34(+) progenitors with FLT3-ligand, thrombopoietin, and stem cell factor induces extensive amplification of a CD34(-)CD14(-) and a CD34(-)CD14(+) dendritic cell precursor.

Current in vitro culture systems allow the generation of human dendritic cells (DCs), but the output of mature cells remains modest. This contrasts with the extensive amplification of hematopoietic progenitors achieved when culturing CD34(+) cells with FLT3-ligand and thrombopoietin. To test whether such cultures contained DC precursors, CD34(+) cord blood cells were incubated with the above cytokines, inducing on the mean a 250-fold and a 16,600-fold increase in total cell number after 4 and 8 weeks, respectively. The addition of stem cell factor induced a further fivefold increase in proliferation. The majority of the cells produced were CD34(-)CD1a- CD14(+) (p14(+)) and CD34(-)CD1a-CD14(-) (p14(-)) and did not display the morphology, surface markers, or allostimulatory capacity of DC. When cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4), both subsets differentiated without further proliferation into immature (CD1a+, CD14(-), CD83(-)) macropinocytic DC. Mature (CD1a+, CD14(-), CD83(+)) DCs with high allostimulatory activity were generated if such cultures were supplemented with tumor necrosis factor-alpha (TNF). In addition, p14(-) cells generated CD14(+) cells with GM-CSF and TNF, which in turn, differentiated into DC when exposed to GM-CSF and IL-4. Similar results were obtained with frozen DC precursors and also when using pooled human serum AB+ instead of bovine serum, emphasizing that this system using CD34(+) cells may improve future prospects for immunotherapy.

Animals↗