Health status and health-related quality of life of municipal waste collection workers - a cross-sectional survey.

BACKGROUND: Waste collection workers are exposed to several occupational stressors which may affect their quality of life. Our aim was to assess the health status and health-related quality of life (HRQoL) of municipal waste collection workers of a big German city. METHODS: Cross-sectional study with a non-random sample of 65 (62 male, 3 female) workers of the Hamburg sanitation department, volunteering to participate in the study. We assessed the prevalence of reported health complaints and health problems. HRQoL was assessed with the self-administered EQ-5D-5L questionnaire and its visual analogue scale (VAS). RESULTS: The most common health problems were musculoskeletal complaints (back pain reported by 67.2 %, other musculoskeletal complaints 15.4 %). Asthma or chronic obstructive pulmonary disease (COPD) was reported by 15.4 % of the workers. All participants reporting having a diagnosis of asthma or COPD had been or were active smokers. Our findings indicate an impaired HRQoL among the investigated occupational group. Regarding EQ-5D 68.3 % reported at least "slight" problems in one or more dimensions, and almost one third (31.7 %) reported "no problems" in any dimension. Problems were most frequently reported in the dimension "pain/discomfort" (64.1 % of the workers). The mean VAS value was 80.9 (13.2). The presence of back pain was associated with limitations in HRQoL (RR 3.1; 95 %-CI 1.5-6.1). The EQ5D VAS score was statistically significantly lower among waste collectors with back pain (77.9 SD 14.1) compared to those with no back complaints (88.0 SD 7.6, p < 0.01). CONCLUSIONS: Back complaints are common among municipal waste collectors and are associated with considerable impairments in their HRQoL. Interventions to enhance ergonomic work are needed in order to reduce back complaints and enhance HRQoL in this occupational group.

Identification of two metallothioneins as novel inhalative coffee allergens cof a 2 and cof a 3.

BACKGROUND: Dust of green coffee beans is known to be a relevant cause for occupational allergic disorders in coffee industry workers. Recently, we described the first coffee allergen (Cof a 1) establishing an allergenic potential of green coffee dust. OBJECTIVE: Our aim was to identify allergenic components of green coffee in order to enhance inhalative coffee allergy diagnosis. METHODS: A Coffea arabica pJuFo cDNA phage display library was created and screened for IgE binding with sera from allergic coffee workers. Two further coffee allergens were identified by sequence analysis, expressed in E. coli, and evaluated by Western blots. The prevalence of sensitization to recombinant Cof a 1, Cof a 2, and Cof a 3 and to commercially available extract was investigated by ELISA (enzyme-linked immunosorbent assay) respectively CAP (capacity test) screening in 18 sera of symptomatic coffee workers. RESULTS: In addition to the previously described chitinase Cof a 1, two Coffea arabica cysteine-rich metallothioneins of 9 and 7 kDa were identified and included in the IUIS Allergen Nomenclature as Cof a 2 and Cof a 3. Serum IgE antibodies to at least one of the recombinant allergens were found in 8 out of 18 symptomatic coffee workers (44%). Only 2 of the analysed sera (11%) had reacted previously to the commercial allergy test. CONCLUSIONS: In addition to the previously described Cof a 1 we have identified two further coffee proteins to be type I coffee allergens (Cof a 2 and Cof a 3) which may have a relevant potential for the specific diagnosis and/or therapy of coffee allergy.

Cof a 1: identification, expression and immunoreactivity of the first coffee allergen.

BACKGROUND: Over the past years, dust of green coffee beans has become known to be a relevant cause for occupational type I allergies. Up to now, allergy diagnostics is based on native green coffee bean extract which exhibits insufficient specificity due to interfering substances as well as batch-to-batch variations. No coffee allergen has been described on the molecular level so far. The aim of this study was to identify the first allergen of green coffee. METHODS: The allergenicity of native green coffee bean extracts was analyzed by means of ImmunoCAP in sera of 17 symptomatic coffee workers. A Coffea arabica pJuFo cDNA phage display library was constructed and screened for IgE binding to coffee proteins with 2 sera from allergic coffee workers. By sequence analysis, a new coffee allergen (Cof a 1) was identified, expressed in Escherichia coli, and evaluated by Western blots. The frequency of sensitization was investigated by ELISA screening. RESULTS: The Cof a 1 cDNA encoded a 32-kDa C. arabica class III chitinase. Serum IgE antibodies to the recombinant allergen were found in 3 out of 17 symptomatic coffee workers (18%), whereas only 2 of them reacted to the commercial allergy test. CONCLUSIONS: A class III chitinase of C. arabica was identified to be the first known coffee allergen Cof a 1. It may have a relevant potential for the specific diagnosis of coffee sensitization.

Health risks due to coffee dust.

OBJECTIVE: This study assessed current health risks due to occupational exposure to coffee dust. METHODS: We performed a cross-sectional study in a coffee haulage company (n = 24), a coffee silo (n = 19), and a decaffeinating company (n = 17). Cross-shift and cross-week case histories of these employees as well as lung function values were recorded. During the handling of green coffee, measurements of airborne dust were conducted. RESULTS: The employees in these workplaces were mainly affected by erythematous and rhinoconjunctival symptoms. They occurred especially in subjects exposed to a high dust load (> 10 mg of inhalable dust per cubic meter of air; n = 28) [Pearson chi(2) test, p = 0.020 and p = 0.023]. IgE antibodies to green coffee and castor beans were detected in 3 workers and 10 workers, respectively. The majority of them (two employees and six employees, respectively) had shown respiratory symptoms during the past 12 months. The preshift lung function values were below average but were not dependent on the level of the inhalable coffee dust exposure. Employees with a coffee dust load > 10 mg/m(3) of air showed higher unspecific bronchial responsiveness more frequently than those with lower exposures. CONCLUSION: During the transshipment (especially during unloading) of green coffee, a high and clinically relevant exposure to irritative and sensitizing dust occurs. Therefore, efforts to reduce these dust exposures are generally recommended.

Identification of wheat gliadins as an allergen family related to baker's asthma.

BACKGROUND: Flour is still one of the most common causes of occupational asthma worldwide. Thus far, little is known about the relevant allergens causing baker's asthma. Therefore the reliability of current diagnostic procedures is insufficient. Only few of the suspected causative wheat allergens have been hitherto characterized on the molecular level. OBJECTIVE: The aim was to identify and characterize unknown wheat allergens related to baker's asthma to improve the reliability of diagnostic procedures. METHODS: A wheat pJuFo cDNA phage display library was created and screened for IgE binding to wheat proteins with pooled sera from patients with baker's asthma. After identifying an alphabeta-gliadin, the frequency of sensitization was investigated by means of ELISA screening of 153 bakers' sera with the recombinant alphabeta-gliadin. Furthermore, the allergenicity of native total gliadin (alphabeta, gamma, omega) was analyzed by means of ImmunoCAP. RESULTS: One cDNA clone was identified as an alphabeta-gliadin. Serum IgE antibodies to the recombinant allergen were found in 12% of bakers with occupational asthma. Of the asthmatic bakers, 33% showed sensitization to native total gliadin; 4% of them had negative results on routine IgE testing with wheat extract. CONCLUSIONS: Gliadins represent a newly discovered family of inhalable allergens in baker's asthma. This finding demonstrates that water-insoluble proteins might also represent causative allergens.

Whole cell ELISA for measuring anti-tumour effects of immunotherapies in a mouse tumour model of ALCL.

The use of whole cell vaccines to augment anti-tumour immunity has been explored throughout the last century. Using the recently established TS1G6 ALCL mouse model, we compared the ability of whole cell vaccines with different combinations of CpG oligodeoxynucleotides, Diphteria-, Pertussis- and Tetanus-vaccine (DPT) to enhance the immunogenicity of tumour cells. We have therefore developed a whole cell ELISA that detects the systemic anti-tumor-cell antibody response. CpG oligodeoxy-nucleotides can induce production of different TH1-cytokines and stimulate immune effector cells. Diphteria-, Pertusis- and Tetanusvaccine, injected together with irradiated tumor cells into Diphteria-, Pertussis- and Tetanus-preimmunized mice were used to serve as a target for the host's existing memory response and thus enhance the immunogenicity of the tumour cells by induction of a local inflammation. The combined application of oligodeoxynucleotides, the vaccines and irradiated tumor cells into preimmunized mice quickly induced very high titers of tumour cell-specific antibody response. We conclude that this therapy may be a new attractive part of a tumour immunization strategy.

Transgenic rat hearts overexpressing SERCA2a show improved contractility under baseline conditions and pressure overload.

OBJECTIVE: The activity of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) is reduced in the failing myocardium. Therefore, transfer of SERCA2a cDNA is considered as a therapeutical approach. The aim of this study was analysis of the long-term effect of SERCA2a overexpression in normal as well as pressure overload challenged myocardium of transgenic rats. METHODS: Independent transgenic rat lines were established expressing the rat SERCA2a cDNA specifically in the myocardium resulting in increased SERCA2a protein levels by 30-70%. Simultaneous measurements of isometric contraction and calcium transients were carried out in right ventricular papillary muscle preparations. Hemodynamic parameters were measured in hearts of unchallenged rats as well as 10 weeks after pressure overload induced by abdominal aortic banding. RESULTS: Analysis of calcium handling and contractile parameters in isolated right ventricular papillary muscles revealed significant shortening of intracellular calcium transients and half maximal relaxation times (RT(50)). Assessing myocardial contractility in working heart preparations, both transgenic rat lines revealed elevated left ventricular pressure, improved systolic and diastolic parameters, attenuated negative force-frequency relation, and a dose-dependent beta-adrenergic effect. Aortic banding resulted in reduction of left ventricular pressure and worsening of contraction and relaxation parameters with no differences in mortality in both transgenic (+dP/dt 3084+/-96 vs. 3938+/-250 mmHg/s; RT(50) 47.0+/-1.2 vs. 36.7+/-1.4 ms) and wild-type rats (+dP/dt 2695+/-86 vs. 3297+/-122 mmHg/s; RT(50) 53.0+/-1.6 vs. 44.1+/-1.4). SERCA2a overexpressing hearts revealed improved hemodynamic parameters compared to wild-type controls. Acceleration of isovolumetric relaxation characterized by the index Tau was directly correlated to SERCA2a protein concentrations. CONCLUSION: Overexpression of SERCA2a protein results in a positive inotropic effect under baseline conditions remaining preserved under pressure overload without affecting mortality. Therefore therapeutic transfer of SERCA2a may become a potential approach for gene therapy of congestive heart failure. Moreover, transgenic SERCA2a rats will be useful for studies of long-term SERCA2a overexpression in further cardiovascular disease models.

Overexpression of NPM-ALK induces different types of malignant lymphomas in IL-9 transgenic mice.

Anaplastic large-cell lymphoma (ALCL) comprises approximately 25% of all non-Hodgkin lymphomas (NHL) in children and young adults, and up to 15% of high-grade NHL in older patients. Over 50% of these tumours carry the translocation t(2;5)(p23;q35). The result of this translocation is the fusion of the nucleophosmin (NPM) gene to the anaplastic lymphoma kinase (ALK) gene. The resulting hybrid protein contains the ALK catalytic domain that consequently confers transforming potential, which contributes to the pathogenesis of ALCL. To further analyse the transforming activity in an animal model, a cDNA encoding the protein product, NPM-ALK, was inserted into the retrovirus vector pLXSN and transduced into mouse bone marrow progenitors. These cells were subsequently used in a bone marrow transplant with the aim of reconstituting the haematopoietic compartments of lethally irradiated recipients. IL-9 transgenic mice were chosen as the animal model system, because dysregulated expression of the IL-9 gene in transgenic mice results in the sporadic development of spontaneous thymic lymphomas. Moreover, IL-9 is known to be expressed in cases of human ALCL. We used 15 IL-9 transgenic mice and eight corresponding wild-type mice (FVB/N) and transplanted them with NPM/ALK infected bone marrow cells. Eight IL-9 transgenic mice, serving as a control group, received pLXSN (vector only)-infected marrow. Reconstituted mice developed NPM-ALK-positive lymphomas, including lymphoblastic lymphomas of T-cell type (T-LB), mature and immature plasmacytoma (PC), and plasmoblastic/anaplastic diffuse large-B-cell lymphoma after about 19-20 weeks. The combined overexpression of NPM-ALK and IL-9 led to the transformation of murine lymphoid cells with accelerated and enhanced development of T-LB in 46% of the mice, which only very rarely occurs in IL-9 transgenic mice only. Of the 15 animals, five (33%) developed plasmacytic/plasmoblastic neoplasms, of which the most aggressive tumours share many features with anaplastic/plasmoblastic diffuse large-B-cell lymphoma on the basis of morphology, a characteristic growth pattern and ALK expression.

Characterization of a novel human anaplastic large cell lymphoma cell line tumorigenic in SCID mice.

L82, a novel anaplastic large cell lymphoma (ALCL) cell line was established from the pleural effusion of a 24-year-old patient with recurrent ALCL. L82 cells showed the typical morphologic features of ALCL cells with irregular, often indented, nuclear profiles, prominent nucleoli, and abundant cytoplasm. The immunoprofile of L82 corresponds to that seen typically in primary ALCL cells, with positivity for CD30, EMA, CD3, CD4, CD25, CD71, TIA1, and granzyme B; the cells were negative for EBV-related antigens. Cytogenetic analysis showed a complex, near triploid karyotype with 72-77 chromosomes, including the ALCL specific translocation t(2;5)(p23;q35). Chromosomal analysis revealed a number of secondary structural alterations including amplification of 7q21-31, 1q, and 6p, and gain of chromosomal material in 8q (affecting the c-myc gene). The rearrangement of the T-cell receptor-gamma locus shows that L82 is clonally derived from T-lineage lymphoid cells. mRNAs for interleukin 7 (IL-7), IL-8, IL-9, IL-10, TNF-beta, and for the IL-7 and IL-9 receptor were found. These data show that the T-helper cell (Th)1/Th2 balance was polarized to Th2. L82 were inoculated intraperitoneally into 4 week-old SCID mice and produced a disseminated tumor within 4-6 weeks. Morphological, immunohistochemical, and molecular genetic investigation confirmed that the xenograft and the original ALCL tumor were identical. SCID mice xenografted with the human ALCL cell line, L82, provide a useful model system for the investigation of the biology of ALCL and of new therapeutic approaches, such as specific immunotherapy.