Objectives This study attempted to determine the prognostic indicators of low-back pain in an occupational health setting. Methods The identification of prognostic factors of (i) functional ...disability after 3 months' follow-up, (ii) functional disability after 12 months' follow-up, and (iii) time to return to work among 120 workers who reported to an occupational health unit and were off work with low-back pain for at least 10 days. Crude and adjusted odds ratios and hazard ratios with 95% confidence intervals were estimated for the 3 outcome measures. Results Factors related to a longer time to return to work were radiating pain, high functional disability at the beginning of the study, problems in relations with colleagues, and high work tempo and work quantity. High functional disability at the beginning of the study and a high avoidance coping style predicted functional disability at 3 months. Functional disability at 12 months was more accurately predicted by work-related and psychosocial factors. Conclusions Especially radiating pain and functional disability predict a long duration of low-back pain in occupational health practice. Occupational physicians should also note work-related and psychosocial characteristics.
Certain functions of the nervous system were examined in 31 printing workers (mean age 44) exposed to trichloroethene (mean duration 16 years) and 28 controls (mean age 45). In the sural nerve the ...conduction velocity (SNCV), response amplitude, and refractory period (SRP) were measured. The latencies of the masseter and the blink reflex were determined to test the trigeminal nerve. In the peroneal nerve the conduction velocity of fast and slow nerve fibres, the response amplitude, and the refractory period were determined. As a measure of autonomic nerve function the response of the heart rate was determined to isometric muscle contraction and deep breathing. Individual cumulative exposure was calculated on the basis of exposure levels in the past. The mean cumulative exposure of the exposed workers was 704 ppm x years. For the assessment of the exposure effect relation a multiple linear regression model was used. A slight reduction (-1.1 m/s) in the SNCV was found and a prolongation (0.4 ms) of the SRP (mean of the controls 1.95 ms). The latency of the masseter reflex (mean 10.4 ms) had increased (0.4 ms). With respect to the blink reflex no prolongation was found. No impairment was found in the functions of motor and autonomic nerves. This study shows that the refractory period may be a sensitive indicator of preclinical toxic neuropathies. Long term exposure to trichloroethene at threshold limit values (about 35 ppm) may slightly affect the trigeminal and sural nerves.
Certain functions of the peripheral and autonomic nervous systems, and colour discrimination were examined in 45 workers (mean age 49; mean exposure to carbon disulphide (CS2) 20 years) and 37 ...controls (mean age 48). Conduction velocity and refractory period of the peroneal and sural nerves were determined. The conduction velocity of the slower fibres of the peroneal nerve was measured by means of an improved method that makes use of the refractory period. Function of autonomic nerves was assessed by measuring the variation in heart rate during rest, during deep breathing, and during isometric muscle contraction. Colour discrimination was evaluated by the Lanthony desaturated test. Individual cumulative exposure to CS2 was calculated on the basis of exposure in the past and individual job history. Mean cumulative exposure was 165 ppm-years. The peroneal nerves of exposed workers showed a decrease (-1.0 m/s) in conduction velocity of the slow fibres and a prolongation (0.1 ms) of the refractory period (mean 1.6 ms) compared with controls. These effects were related to cumulative exposure. No impairment of function of the sural nerve or of colour discrimination was found. The muscle heart reflex was decreased in the exposed group, but this was not related to cumulative exposure. This study has established more firmly that a decrease in conduction velocity of slow motor fibres occurs at low levels of exposure to CS2. Extrapolation of the results suggests that small effects may occur after 40 years of exposure to concentrations below the present threshold limit value (10 ppm).
Abstract
FcεRI is suspected to play a pivotal role in the pathophysiology of atopic disorders such as atopic dermatitis. In search for genes differentially regulated by FcεRI on APCs, a differential ...cDNA bank of receptor-stimulated and unstimulated monocytes was established. By means of suppression subtractive hybridization, we identified kynurenine 3-monooxygenase and subsequently indoleamine 2,3-dioxygenase (IDO) to be overexpressed in FcεRI-activated monocytes. IDO is the rate-limiting enzyme in the catabolism of the essential amino acid tryptophan. We show that cross-linking of FcεRI on monocytes results in low tryptophan concentrations associated with impaired T cell stimulatory capacity. Importantly, T cell suppression could be prevented by the addition of tryptophan or inhibition of IDO. Moreover, stimulation of T cells by FcεRI-activated monocytes was increased compared with T cell stimulation by nonactivated monocytes if exogenous supply of tryptophan was available. We speculate that the expression of IDO by FcεRI+ APCs in vivo allows these cells to regulate T cell responses in atopic disorders by inhibiting or stimulating T cell proliferation, depending on the metabolic environment.
Langerhans cells (LC) are a special subset of dendritic cells integrating cutaneous immunity. The study of LC function is of major interest not only for efforts of vaccine design and immunotherapy ...but also for gaining an insight into the pathogenesis of immune-mediated cutaneous diseases and neoplasias. Recently, defined antigen-presenting cells were described that express indoleamine 2,3-dioxygenase (IDO) and inhibit T cell proliferation in vitro and in vivo. Here, we show that stimulation with interferon-γ (IFN-γ) induces the expression of functionally active IDO in highly purified human epidermal LC. The induction of IDO after stimulation of LC with IFN-γ seems to follow a defined kinetic with rapid upregulation followed by a downregulation after about 24 h of culture. Accordingly, proliferation of T cells induced by anti-CD3 antibodies was modulated by supernatants of IFN-γ-activated human epidermal LC. Importantly, downregulation of T cell proliferation by supernatants of 24 h IFN-γ-activated LC was prevented by inhibition of IDO. These results indicate that LC not only have the capacity to stimulate but also to inhibit T cells, and suggest that LC possess an immunoregulatory function in promoting T cell tolerance by production of IDO.
Neurotoxic effects associated with long term low level occupational exposure to CS2 were reinvestigated four years after the initial study in the same group of workers. The second study concerned 44 ...exposed and 31 matched control workers. For both studies a personal cumulative exposure Ec was calculated based on function specific exposure levels and the occupational histories, which were carefully re-established. The exposed workers' average Ec was 192 and 213 ppm-years (first and second study respectively). Where possible the values of both data sets were used in a final combined analysis. Effects were found on the motor nerve conduction velocity of the fast (-0.9 m/s) and slow (-1.0 m/s) fibres of the peroneal nerve, the sensory nerve conduction velocity in the hand and arm segment of the median (-2.1 m/s) and ulnar (-1.3 m/s) nerves, and in the sural nerve (-1.3 m/s). An increased refractory period was found in the sural nerve (+ 0.2 ms, + 11%), but not in the peroneal nerve. For the autonomic nervous system an effect was found on the heart frequency response to isometric muscle contraction (-4.7 beats/min, -26%) and maximal forced respiration (-3.2 beats/min, -16%). This study shows the importance of a detailed evaluation of past exposure data. The reinvestigation enabled a more precise estimation of the effects of CS2, which is particularly desirable at around threshold exposure.
Dendritic cells (DCs) present antigens to T cells via CD1, HLA class I or class II molecules. During maturation, HLA class II‐restricted presentation is optimized. The relocalization of CD1e from ...Golgi to endosomal compartments during DC maturation suggests also an optimization of the antigen‐presentation pathway via CD1 molecules. We here detail the biosynthesis and cellular pathway of CD1e in immature and maturing DCs. Unlike the other CD1 molecules, CD1e was found to reach late endosomes through sorting endosomes, without passing through the plasma membrane in either immature or maturing cells. After induction of DC maturation, CD1e disappeared rapidly from the Golgi and was transiently localized in HLA‐DR+ vesicles, while the number of CD1e+/CD1b+ compartments increased for at least 20 h. High‐resolution light microscopy showed that, in immature DCs, CD1e+ vesicles were often in close apposition to EEA1+ or HLA‐DR+ compartments, while CD1e displayed a nearly exclusive distribution in the lysosomes of mature DCs, a finding corroborated by immunoelectron microscopy. During maturation, CD1e synthesis progressively declined, while the endosomal cleavage of CD1e still occurred. Thus, CD1e displays peculiar properties, suggesting an unexpected role among the family of CD1 antigen‐presenting molecules.
Pure Red-Cell Aplasia Nathan, D G; Sieff, C A
The New England journal of medicine,
06/1999, Letnik:
340, Številka:
25
Journal Article
Recenzirano
To the Editor:
Handgretinger et al. (Jan. 28 issue)
1
present evidence that a clone of large granular lymphocytes induced pure red-cell aplasia by attacking erythroid progenitors with a deficiency of ...HLA class I antigens. They show that glycophorin A+ erythroblasts normally express low levels of HLA class I antigens and that they are lysed by the clonal cells.
But the authors provide almost no data that can explain why granulocytes are unaffected in the disease. They made no attempt to lyse myeloblasts in vitro or to measure the expression of HLA class I antigens as a function of a myeloid . . .
Dendritic cells express several alternatively spliced CD1e mRNAs. These molecules encode proteins characterized by the presence of either one, two, or three α domains and either a 51- or 63-amino ...acid cytoplasmic domain. Moreover, mRNAs encoding isoforms lacking the transmembrane domain are observed. Several of these CD1e isoforms were expressed in transfected cells, and two of them, with three α domains, displayed a particular processing pathway. These latter isoforms slowly leave the endoplasmic reticulum due to the presence of atypical dilysine motifs in the cytoplasmic tail. These molecules are associated with the β2-microglobulin and accumulate in late Golgi and late endosomal compartments. In the latter compartments, they are cleaved into soluble forms that appear to be stable. In dendritic cells, these isoforms are mainly located in the Golgi apparatus, and upon maturation they are redistributed to late endosomal compartments. This work demonstrates the existence of CD1e molecules. As compared with other CD1 molecules, CD1e displays fundamentally different properties and therefore may represent a third type of CD1 molecules.
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