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PubMedDate not supplied

Occupational asthma.

Occupational asthma is the most common occupational lung disease in the world. Occupational asthma comprises approximately 25-50% of occupational lung diseases and is responsible for up to 15% of all asthma cases. Either immunologic or nonimmunologic causes may be responsible for occupational asthma. There are approximately 250 compounds known to cause occupational asthma. Common examples include flour, animal dander, isocyanates, and latex. The diagnosis of occupational asthma depends on an accurate history of asthma and documentation that the asthma is caused by workplace exposure. Peak flow measurements are commonly used to provide data to define this relationship. Spirometry and bronchial provocation testing are also helpful. The key management tool in occupational asthma is avoidance of the causative agent. Avoidance is more important than treatment with medications. Occupational asthma can have major socioeconomic impacts on an individual, and the diagnostic work-up and management needs to be performed with this in mind.

Asthma↗
PubMed1998

[VIDAS Stallertest: clinico-biological evaluation of a new global test for respiratory allergy].

"VIDAS Stallertest" is a new screening test for breathing allergy. It allows the detection of 10 different lung specific allergens including domestic acarids (D1), pollents (G3, W6, W21, T3 and T9), pets dander (E1 and E2), moulds (M6), cockroach (16). The method is an immunoenzymatic reaction that contains a cartridge and a cone that is cover with the allergen's mixture and is automated on the VIDAS system. The results are compared to various skin tests analyzed by instantaneous reading for 102 patients. "VIDAS Stallertest" shows an excellent agreement (93%) with the allergic patients as well as with those that are not. The specificity of the new screening test is very high (91%). A comparative study between "VIDAS Stallertest" and "Phadiatop" performed on 155 consultants in allergist office shows a correlation of 93%, a sensitivity and a specificity of 91 and 95%, respectively. "VIDAS Stallertest" is a reliable method in first intention for the general practitioner who faces a putative breathing allergy. Moreover, this is an excellent biological check-up for a questionable or negative skin test.

Allergens↗
PubMed1999

T cell epitopes of a lipocalin allergen colocalize with the conserved regions of the molecule.

In this study we characterized the human T cell-reactive sites of the major cow dander allergen, Bos d 2, a member of the lipocalin protein family. We showed that Bos d 2 contains only a limited number of epitopes. This is in contrast to many other allergens, which usually contain multiple T cell epitopes throughout the molecule. The epitopes of Bos d 2 were primarily concentrated in the conserved regions of the molecule. One of the epitopes was recognized by all the cow-asthmatic individuals regardless of their HLA phenotype. Computer-predicted T cell epitopes on Bos d 2, other lipocalin allergens, and human endogenous lipocalins were situated in similar locations on these molecules and corresponded to experimentally identified epitopes on Bos d 2. The results suggest that human endogenous lipocalins could be involved in the modulation of immune responses against exogenous lipocalin allergens. In addition, our findings are likely to facilitate the development of new forms of immunotherapy against allergies induced by the important group of lipocalin allergens.

Allergens↗
PubMed1994

External four-channel tocography during delivery.

OBJECTIVE: A four-channel tocographic technique was developed in order to improve present knowledge of spatial uterine motility. METHOD: Fifty-four women were monitored during labor. Four pressure transducers were attached in a square around the umbilicus. RESULTS: The origin of uterine contractions was generally determined to be in the upper right segment of the uterus. The rate of operative deliveries was decreased in the case of predominant upper right origin of labor. Most of the contractions with clear propagation patterns originated on the upper right side, continued to the left and then spread to the lower right part of the uterus. The highest relative intensity was also measured on the upper right side. CONCLUSION: Predominant upper right origin of labor may be important for unassisted or spontaneous delivery.

Adult↗
PubMed1983

Effects of the cold pressor test on the left ventricular function of patients with coronary artery disease.

We used the cold pressor test as provocative of myocardial ischemia in 23 subjects evaluated for chest pain on effort. Seven of them (group N) had normal coronary arteries, and 16 (group CAD) had critical stenoses along the main branches of the left coronary artery. In both groups exposure to cold induced increase in arterial pressure and double product. Left ventricular end-diastolic pressure increased +60% from baseline (P less than 0.001). Angiocardiographic parameters, unchanged in group N, showed an impairment of left ventricular function in group CAD. End-diastolic volume increased +11% (P less than 0.01), ejection fraction decreased -8% (P less than 0.0025), with a significant reduction in segmental wall motion in the area of the diseased artery (P less than 0.001). The mean Vcf was slightly and not significantly reduced, while early-systolic and end-diastolic stress and the constant of stiffness consistently increased in both groups. The appearance or extension of ventricular wall contraction abnormalities in group CAD, in the absence of demonstrable coronary spasm and in the presence of a remarkable increase in left ventricular end-diastolic pressure and stress, was interpreted as due to ischemia secondary to increased extravascular resistances to coronary flow. The cold pressor test is proposed as a useful tool for the diagnosis and evaluation of patients with ischemic heart disease.

Adult↗
PubMed2006

Characterization of in vitro migratory properties of anti-CD19 chimeric receptor-redirected CIK cells for their potential use in B-ALL immunotherapy.

OBJECTIVE: Cytokine-induced killer (CIK) cells are ex vivo expanded cells enriched in CD3(+)CD56(+) natural killer T (NKT) cells with major histocompatibility-unrestricted cytotoxicity against several tumoral targets, except B-lineage acute lymphoblastic leukemia (B-ALL). We redirected CIK cells cytotoxicity toward B-ALL with a chimeric receptor specific for the CD19 antigen and then explored if modified-CIK cells maintain the same chemotactic properties of freshly isolated NKT cells, whose trafficking machinery reflects their preferential localization into the sites of B-ALL infiltration. MATERIAL AND METHODS: CIK cells were expanded ex vivo for 21 days and analyzed for expression of adhesion molecules and chemokine receptors regulating adhesion and homing toward leukemia-infiltrated tissues. CIK cells were then transduced with the anti-CD19-zeta-internal ribosomal entry site-green fluorescent protein retroviral vector and characterized for their cytotoxicity against B-ALL cells in a (51)Cr-release assay and for their trafficking properties, including chemotactic activity, adhesion and transendothelial migration, and metalloproteases-dependent invasion of Matrigel. RESULTS: Similarly to freshly isolated NKT cells, CD49d and CD11a were highly expressed on CIK cells. Moreover, CIK cells expressed CXCR4, CCR6, and CCR7 (mean expression 72%, 60%, and 32%, respectively), presenting chemotactic activity toward their respective ligands. Anti-CD19 chimeric receptor-modified CIK cells became cytotoxic against B-ALL cells (mean lysis, 60%) and showed, after exposure to a CXCL12 gradient, high capacity to adhere and transmigrate through endothelial cells and to invade Matrigel. CONCLUSION: The potential capacity to localize into leukemia-infiltrated tissues of anti-CD19 chimeric receptor-redirected CIK cells, together with their ability to efficiently kill B-ALL cells, suggests that modified-CIK cells represent a valuable tool for leukemia immunotherapy.

Antigens, CD↗
PubMed2004

Defective dendritic cell migration and activation of adaptive immunity in PI3Kgamma-deficient mice.

Gene-targeted mice were used to evaluate the role of the gamma isoform of phosphoinositide 3-kinase (PI3Kgamma) in dendritic cell (DC) migration and induction of specific T-cell-mediated immune responses. DC obtained from PI3Kgamma-/- mice showed a reduced ability to respond to chemokines in vitro and ex vivo and to travel to draining lymph nodes under inflammatory conditions. PI3Kgamma-/- mice had a selective defect in the number of skin Langerhans cells and in lymph node CD8alpha- DC. Furthermore, PI3Kgamma-/- mice showed a defective capacity to mount contact hypersensitivity and delayed-type hypersensitivity reactions. This defect was directly related to the reduced ability of antigen-loaded DC to migrate from the periphery to draining lymph nodes. Thus, PI3Kgamma plays a nonredundant role in DC trafficking and in the activation of specific immunity. Therefore, PI3Kgamma may be considered a new target to control exaggerated immune reactions.

Animals↗
PubMed2006

T cells stimulated by CD40L positive leukemic blasts-pulsed dendritic cells meet optimal functional requirements for adoptive T-cell therapy.

Adoptive T-cell immunotherapy may provide complementary therapy for childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In this study, we have analyzed the functional characteristics of anti-BCP-ALL effector T cells generated by co-culturing T lymphocytes and dendritic cells (DC) from allogeneic human stem cell transplantation (HSCT) donors. After 21-day co-culture with DC pulsed with CD40L+ apoptotic BCP-ALL blasts, T cells presented with both effector and central memory phenotype, and showed high and specific cytotoxic activity against leukemic cells (average lysis = 77%), mostly mediated by CD8+ T cells. Noticeably, growth of CD4 T cells was maintained (45% of total cells), which actively produced Th1 cytokines (IFN-gamma, TNF-alpha, IL-2), but not IL-4, IL-5 and IL-10. Anti-BCP-ALL T cells expressed CD49d and CXCR4 (implicated in the recruitment to bone marrow), and CD62L and CCR7 (involved in the migration to lymphoid organs). In accordance with this profile, T cells significantly migrated in response to the chemokines CXCL12 and CCL19. In conclusion, stimulation of T cells with CD40L+BCP-ALL cells-loaded DC not only elicited the generation of potent and specific anti-leukemic cytotoxic effectors, but also the differentiation of specific and functional Th-1 CD4 lymphocytes. These effectors are fully equipped to reach leukemia-infiltrated tissues and have characteristics to support and orchestrate the anti-tumor immune-response.

Adoptive Transfer↗
PubMed1979

Biological role of gramicidin S in spore functions. Studies on gramicidin-S-negative mutants of Bacillus brevis ATCC9999.

Gramicidin-S-negative mutants of Bacillus brevis ATCC9999 have been isolated with a remarkly higher yield after ethidium bromide or acridine orange treatment, than after N-methyl-N'-nitro-N-nitrosoguanidine treatment. Four (MIV, Smr170, R5 and EB 16) of 38 isolated mutants were characterized with respect to the lesion in gramicidin-S-synthesizing activity. The mutants sporulate to the same extent as the parental strain except mutant Smr 170 which sporulates less. However, mutant spores were more heat-sensitive and possessed a reduced level of dipicolinic acid content. No significant difference was observed in the germination time of wild-type and mutant spores. All spores germinated after 80--110 min, but the outgrowth time was different: all gramicidin-S-negative mutants grew out immediately after germination whereas wild-type spores required a lag period of 9--10 h. When the mutants were allowed to sporulate in the presence of gramicidin S, the spores were found to be heat-resistant and their outgrowth postponed to the same period as the parent spores. The addition of gramicidin also eliminated the deficiency of dipicolinic acid. A new class of gramicidin-S-negative mutant, R5, which only activates L-valine and L-leucine, is described. A possible biological function of gramicidin S in the heat-resistance and in the timing of spore outgrowth is discussed.

Acridine Orange↗
PubMed1982

Antibacterial action of gramicidin S and tyrocidines in relation to active transport, in vitro transcription, and spore outgrowth.

The cyclopeptide antibiotic gramicidin S or tyrocidine in concentrations of 2 to 4 mumol/mg of membrane protein inhibited the active transport of [3H]alanine and [3H]uridine in membrane vesicles isolated from Bacillus brevis and Bacillus subtilis. We used one analog of gramicidin S and two of tyrocidine A to study the relationship between peptide structure and antibacterial action as seen in inhibiting active transport and in vitro transcription and in delaying spore outgrowth. The data showed that [Ser2,2']-gramicidin S, in which the two ornithine residues were replaced by two serines, was at least 50 times less active antibacterially and gave a low response in transport inhibition and delay of spore outgrowth compared with the natural peptide. The antibacterial activity of [Val6]-tyrocidine A was twice lower than that of tyrocidine A, and it also showed a considerable reduction in transport and transcription inhibition. [Orn7]-tyrocidine A containing two ornithine residues in positions corresponding to those in gramicidin S was almost inactive in all functions tested. The correlation between peptide structure and activity is discussed.

Alanine↗
PubMed1976

Cardiomyopathy complicated by left ventricular aneurysms in children.

Ventricular aneurysms in children are unusual. Three patients with cardiomyopathy associated with angiographically proved left ventricular aneurysms in this age group are reported. Two of them were girls. The ages were 20 months, 7 years, and 14 years. Heart failure was present in all patients. There was radiological evidence of cardiomegaly in all three, and the electrocardiogram showed signs of necrosis in two of them. Selective left ventricular angiography disclosed generalized hypokinesis in all patients. One child had an aneurysm of the diaphragmatic wall. In another the aneurysm was localized in the muscular ventricular septum, causing severe subpulmonary stenosis by encroaching in the right ventricular outflow tract during systole. The third patient had an aneurysm of the left ventricular free wall partly encircling the left ventricle. The coronary arteries appeared normal in all cases. The clinical features of the underlying disease were not altered by the presence of the aneurysm except in the patient with the septal aneurysm and subpulmonary stenosis. In this patient the aneurysm was successfully resected.

Adolescent↗
PubMed2000

Differential expression of cell-cell adhesion proteins and cyclin D in MEK1-transdifferentiated MDCK cells.

Overexpression of a constitutively active mutant of the mitogen-activated protein kinase kinase MEK1 (caMEK1) in epithelial Madin-Darby canine kidney (MDCK)-C7 cells disrupts morphogenesis, induces an invasive phenotype, and is associated with a reduced rate of cell proliferation. The role of cell-cell adhesion molecules and cell cycle proteins in these processes, however, has not been investigated. We now report loss of E-cadherin expression as well as a marked reduction of beta- and alpha-catenin expression in transdifferentiated MDCK-C7 cells stably expressing caMEK1 (C7caMEK1) compared with epithelial mock-transfected MDCK-C7 (C7Mock1) cells. At least part of the remaining alpha-catenin was coimmunoprecipitated with beta-catenin, whereas no E-cadherin was detected in beta-catenin immunoprecipitates. In both cell types, the proteasome-specific protease inhibitors N-acetyl-Leu-Leu-norleucinal (ALLN) and lactacystin led to a time-dependent accumulation of beta-catenin, including the appearance of high-molecular-weight beta-catenin species. Quiescent as well as serum-stimulated C7caMEK1 cells showed a higher cyclin D expression than epithelial C7Mock1 cells. The MEK inhibitor U-0126 inhibited extracellular signal-regulated kinase phosphorylation and cyclin D expression in C7caMEK1 cells and almost abolished their already reduced cell proliferation rate. We conclude that the transdifferentiated and invasive phenotype of C7caMEK1 cells is associated with a diminished expression of proteins involved in cell-cell adhesion. Although beta-catenin expression is reduced, C7caMEK1 cells show a higher expression of U-0126-sensitive cyclin D protein.

Animals↗
PubMed1991

Cerebral vasospasm evaluated by transcranial Doppler ultrasonography at different intracranial pressures.

The present study evaluates the interdependence of clinical stage, cerebral vasospasm, intracranial pressure (ICP), and transcranial Doppler ultrasonographic parameters. The mean flow velocity of blood in the middle cerebral artery and the index of cerebral circulatory resistance as a measure of the peripheral vascular flow resistance were determined in 76 patients with spontaneous subarachnoid hemorrhage. The ICP was measured using an epidural transducer in 41 patients. There was no case in which both high ICP and a high mean flow velocity were observed simultaneously. The investigations led to the following conclusions. 1) In patients with a resistance index of less than 0.5, changes in the mean flow velocity seem to reflect sufficiently the actual severity and time course of vasospasm. 2) During the time course of vasospasm, an increase in the resistance index above values of 0.6 with a simultaneously decreased mean flow velocity indicates a rise in ICP rather than a reduction in vasospasm. 3) With a pronounced increase in ICP, evaluation of the severity and time course of vasospasm by transcranial Doppler ultrasonography based solely upon the mean flow velocity can lead to false-negative results.

Adult↗