Embodiment of action-related language in the native and a late foreign language - An fMRI-study.

Theories of embodied cognition postulate that language processing activates similar sensory-motor structures as when interacting with the environment. Only little is known about the neural substrate of embodiment in a foreign language (L2) as compared to the mother tongue (L1). In this fMRI study, we investigated embodiment of motor and non-motor action verbs in L1 and L2 including 31 late bilinguals. Half had German as L1 and French as L2, and the other half vice-versa. We collapsed across languages to avoid the confound between language and order of language acquisition. Region of interest analyses showed stronger activation in motor regions during L2 than during L1 processing, independently of the motor-relatedness of the verbs. Moreover, a stronger involvement of motor regions for motor-related as compared to non-motor-related verbs, similarly for L1 and L2, was found. Overall, the similarity between L1 and L2 embodiment seems to depend on individual and contextual factors.

From swing to cane: Sex differences of EEG resting-state temporal patterns during maturation and aging.

While many insights on brain development and aging have been gained by studying resting-state networks with fMRI, relating these changes to cognitive functions is limited by the temporal resolution of fMRI. In order to better grasp short-lasting and dynamically changing mental activities, an increasing number of studies utilize EEG to define resting-state networks, thereby often using the concept of EEG microstates. These are brief (around 100 ms) periods of stable scalp potential fields that are influenced by cognitive states and are sensitive to neuropsychiatric diseases. Despite the rising popularity of the EEG microstate approach, information about age changes is sparse and nothing is known about sex differences. Here we investigated age and sex related changes of the temporal dynamics of EEG microstates in 179 healthy individuals (6-87 years old, 90 females, 204-channel EEG). We show strong sex-specific changes in microstate dynamics during adolescence as well as at older age. In addition, males and females differ in the duration and occurrence of specific microstates. These results are of relevance for the comparison of studies in populations of different age and sex and for the understanding of the changes in neuropsychiatric diseases.

Recovery of functional memory T cells in lung transplant recipients following induction therapy with alemtuzumab.

Profound T-cell depletion with the monoclonal antibody alemtuzumab facilitates reduced maintenance immunosuppression in abdominal and lung transplantation. While the phenotype of the post-depletional T cells has been characterized, little is known about their function. In the present study, global and CMV-specific T-cell function was assessed longitudinally in 23 lung transplant (LTx) recipients using T-cell assays (ImmuKnow and T Cell Memory, Cylex, Columbia, MD) during the first year posttransplant after induction therapy. Recovery of mitogen responses were seen at 2 weeks posttransplantation (65%PHA; 58% Con A), despite the low number of circulating T cells (<2%). These responses declined at 4-5 months (24%PHA; 54% Con A) and were partially reconstituted by 9 months (46% PHA; 73% Con A). CMV-specific responses recovered in 80% of R+ patients as early as 2 weeks posttransplant (n = 5) and 72% of patients had a memory response by 3 months (n = 11). In contrast, only 2 of 5 patients who did not exhibit memory responses pre-transplant (R-) developed transient CMV-specific T-cell responses. Our results show that profound depletion of T cells induced by alemtuzumab spares the functional subset of CMV-specific memory T cells. Conversely, CMV R- patients predepletion may require a prolonged period of prophylaxis.

Establishing pediatric immune response zones using the Cylex ImmuKnow assay.

For all transplant patients, the transplant physician must balance the risk of rejection caused by under-immunosuppression against the risk of drug toxicity, secondary infections and post-transplant lymphoproliferative disorder with over-immunosuppression. A Food and Drug Administration (FDA)-approved in vitro assay, the Cylex ImmuKnow assay, provides a global assessment of cellular immune function to help monitor the immune status of immunosuppressed patients. This assay uses the plant lectin phytohemagglutinin to stimulate lymphocytes; an ATP assay is then used to measure the degree of activation of CD4 T cells. However, the normal values for this assay were developed with healthy adult patients. In this study, we determined the normal ranges for the ImmuKnow assay in healthy children and compared those values to levels obtained in healthy adults and in stable pediatric renal transplant patients. We found that healthy children 12 yr of age and older showed immune function levels indistinguishable from adults, while healthy children under 12 had significantly lower immune function levels than adults. For adults, the ImmuKnow assay zones (in ng/mL ATP) of strong, moderate and low immune function correspond to >525, 225 to 525, and <225. In children under 12, we found the corresponding zones to be >395, 175-395 and <175 ng/mL. The median value for normal adults is 415, whereas it is only 295 for children <12 yr of age and this value decreases to 165 in stable renal transplant patients <12 yr of age (compared with 258 for stable adult renal transplant patients). Thus, this study provides critical information necessary to utilize the ImmuKnow assay with pediatric patients. In adults, the degree of immune function as assessed by the ImmuKnow assay helps to predict patients at risk for infection or rejection. If further studies in pediatric patients document the same and is true for children, then the ImmuKnow assay will provide a useful adjunct tool to prevent over- or under-immunosuppression as newly developed drugs are utilized or drug treatment is altered because of drug side effects, toxicity, concurrent illnesses or rejection.

Combining UASB technology and advanced oxidation processes (AOPs) to treat food processing wastewaters.

UASB treatment of fruit cannery and winery effluents was shown to be feasible. However, the treated effluents still have residual COD levels well above the legal limit of 75 mg.l(-1) for direct discharge to a water system and a form of post-treatment is necessary to reduce the COD further. Ozone and ozone/hydrogen peroxide were used in combination with a granular activated carbon contacting column to assess the effectiveness as a post-treatment option for the UASB treated fruit cannery and winery effluent. Colour reduction in the effluents ranged from 66 to 90% and COD reductions of 27-55% were achieved. The combination of ozone and hydrogen peroxide gave better results than ozonation alone. Significant progress was thus made in achieving the legal limit of 75 mg.l(-1).

An immune-based assay for HIV disease management.

Today, patients infected with HIV are monitored routinely for their levels of CD4+ T cells and viral load. Since either or both of these parameters are often discordant with the clinical course, the direct measurement of immune function to more accurately reflect clinical status is needed (Figure 3). The in vitro CMI test provides a rapid method for assessing cell-mediated immunity and is an important adjunct to the clinical management of these patients.

Measurement of T-lymphocyte responses in whole-blood cultures using newly synthesized DNA and ATP.

The proliferative response is most frequently determined by estimating the amount of [(3)H]thymidine incorporated into newly synthesized DNA. The [(3)H]thymidine procedure requires the use of radioisotopes as well as lengthy periods of incubation (>72 h). An alternative method of assessing T-lymphocyte activation in whole-blood cultures involves the measurement of the nucleotide ATP instead of [(3)H]thymidine incorporation. In addition, the Luminetics assay of T-cell activation measures specific T-lymphocyte subset responses through the use of paramagnetic particles coated with monoclonal antibodies against CD antigens. This assay permits rapid (24 h) analysis of lymphocyte subset activation responses to mitogens and recall antigens in small amounts of blood.

Homogeneous model immunoassay of thyroxine by phase-modulation fluorescence spectroscopy.

We describe a homogeneous competitive model immunoassay for determination of thyroxine by multifrequency phase-modulation fluorescence. Using a nonradiative energy transfer transduction mechanism, B-phycoerythrin conjugated to thyroxine is the energy donor and a carboxymethylindocyanine dye conjugated to anti-thyroxine antibody is the energy acceptor. Energy transfer from B-phycoerythrin to the acceptor results in a decreased lifetime and/or phase angle. The fluorescence lifetime change reflects the extent of energy transfer. In the competitive immunoassay format, the donor-thyroxine conjugate and an analytical sample of thyroxine compete for acceptor-antibody binding sites, resulting in a phase angle change which is dependent on the amount of thyroxine in the sample. Dose-response curves of phase angle versus thyroxine concentration are comparable to steady-state intensity curves. Since phase-modulation lifetime measurements are largely independent of total signal intensity, sources of optical interference are minimized. The potential for whole blood measurements exists since the energy transfer lifetime method can be extended to longer wavelengths.

Antibody to human lymphotropic virus type III: immunologic status of homosexual contacts of patients with the acquired immunodeficiency syndrome and the acquired immunodeficiency-related complex.

Twenty homosexual men who reported having sexual contact with homosexual men who had the acquired immunodeficiency syndrome (AIDS) or the AIDS-related complex were examined to determine their clinical status, immunologic profiles, and the presence of antibody to the human T-cell lymphotropic virus type III (HTLV-III). Of the 20, eight men had one or more signs or symptoms of the AIDS-related complex and 12 were asymptomatic. Antibodies to HTLV-III were present in 14 (70%) of 20 of the sexual contacts as compared with four (10%) of 40 healthy homosexuals without known contact with a patient who had AIDS (P less than .0001). Seropositive contacts had significantly higher mean counts of suppressor lymphocytes and lower helper: suppressor ratios (P less than .05 and .005, respectively) and higher serum levels of IgG than seronegative contacts (P less than .05). It was not possible to determine significant differences in sexual practices, drug use, length of relationship, or numbers of different sexual partners between symptomatic and asymptomatic contacts or between seropositive and seronegative contacts in this study.

HTLV-III/LAV infection in hemodialysis patients.

Twenty-five (4.8%) of 520 hemodialysis patients were seropositive for antibody to human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) by enzyme immunoassay. Four had high reactivity on enzyme immunoassay and positive results of Western blot tests, and one of the four had a positive culture. The remaining 21 seropositive patients had low reactivity on enzyme immunoassay, negative results of Western blot tests, and negative cultures. All had received blood transfusions and 19 had antibodies to antigens associated with the H9 cell line used to propagate HTLV-III for serological tests. We found that HTLV-III/LAV was not transmitted in the dialysis centers. Frequent blood transfusion places dialysis patients at risk for HTLV-III/LAV infection, but may more commonly lead to false-positive results of enzyme immunoassay tests.

Distinctive immunological properties of cultured murine thymic epithelial cells.

Skin painting with chemically reactive haptens induces a hapten-specific state of hypersensitivity that is long lasting and can be transferred to unirradiated recipient mice. A similar state of hapten-specific contact sensitivity can be induced by intravenous immunization with hapten-conjugated cells. Thus far, only two cell types have been described that can perform this function: Langerhans cells of the skin, and splenic dendritic cells. All other types, coupled with hapten, induce either tolerance or a short-lived state of contact hypersensitivity that is readily suppressed, and cannot be transferred to normal recipients. In the present experiments, it was demonstrated that culture-enriched, hapten-coupled thymic epithelial cells can also induce a state of stable contact hypersensitivity identical to that induced by skin painting. This provides evidence that thymic epithelial cells have distinctive properties as antigen-presenting cells in vivo. The relationship of this finding to the postulated role of thymic epithelium in T-cell development is discussed.

Biosynthesis of glycosaminoglycans by epithelial and lymphocytic components of murine thymus.

Interactions between the epithelial and lymphocytic components of the thymus are required for T cell maturation, yet the molecular bases for these interactions remain elusive. In the development and function of other endodermally derived organs, glycosaminoglycan-containing proteins are known to play a critical role. In contrast, virtually nothing is known about the macromolecules that are major constituents of thymic interstitial spaces. For these reasons, we undertook metabolic labeling studies in vitro with D-(6-3H)glucosamine and 35SO4(-2) to begin to characterize systematically the relative amounts and types of glycosaminoglycans made by enriched subpopulations of cells within the thymus. Hydrocortisone, which depletes the thymus of 90% of its lymphocytes, was used both to enrich for epithelium-derived glycoconjugates and to determine if significant alterations in glycoconjugate metabolism accompany drug-induced premature thymic involution. Results indicate: 1) glycosaminoglycans account for a substantial proportion of the total glycoconjugates synthesized by both thymocytes and epithelium; 2) Glycosaminoglycans show a tissue-specific distribution. Hyaluronic acid is the major glycosaminoglycan synthesized by thymic epithelium, whereas it accounts for less than 15% of the total glycosaminoglycans made by thymocytes; 3) Similar proportions of sulfated glycosaminoglycans are made by thymic epithelium and thymocytes. Chondroitin sulfates predominate (75 to 90%) over heparan sulfates (10 to 25%). Chondroitin sulfates from both nonstimulated thymocytes and epithelium are nearly exclusively sulfated at the 4-position of their N-acetylgalactosamine residues; 4) The major high m.w. glycoconjugate of thymocytes, however, is nonsulfated and is resistant to pronase, hyaluronidase, chondroitinase ABC, nitrous acid, keratanase, and neuraminidase; 5) Although hydrocortisone treatment causes a dramatic inhibitory effect on the incorporation of radioactivity into smaller oligosaccharide side-chains by "cortisone-resistant" thymocytes, the drug exerts negligible effects on the metabolism of glycoconjugates by epithelium. These data, which quantify and categorize the complex arrays of glycoconjugates synthesized by the major cell types of the thymus, establish the necessary foundations for further investigations into the functional roles of these glycoconjugates in thymic epithelium-induced maturation of T lymphocytes.

Specialized antigen-presenting cells. Splenic dendritic cells and peritoneal-exudate cells induced by mycobacteria activate effector T cells that are resistant to suppression.

We have tested the ability of several types of trinitrophenyl (TNP)-labeled Ia+ cells to induce contact hypersensitivity (CS) after intravenous injection. Most labeled cell types (spleen cells, splenic macrophages, various types of peritoneal-exudate cells) not only fail to induce CS after this type of inoculation but, rather, activate T suppressor cells leading to specific immunological tolerance. Occasionally, some of these immunizing cells managed to bypass the T suppressor system and induced CS. In those cases the response was short-lived and could be blocked by concomitant injection of trinitrobenzelsulphonic acid (TNBS), a potent inducer of T suppressor cells. In sharp contrast to these results, TNP-labeled splenic dendritic cells and TNP-labeled peritoneal-exudate cells induced by complete Freund's adjuvant had the following distinctive features: (a) They were always able to sensitize when injected intravenously, and the degree of sensitization they produced was roughly equivalent to that achieved by cutaneous application of picryl chloride, the chemically reactive form of TNP. (b) The response they elicited was long lived (i.e., lasted for greater than 3 wk). (c) Their sensitizing capacity could not be blocked by the concomitant injection of TNBS. (d) They elicited a response that could be adoptively transferred to untreated, normal recipients. These results indicate that the type of cell that first presents antigen to the immune system plays an important, even essential, role in determining the strength and duration of the subsequent immune response. In particular, the results suggest that some special antigen-presenting cells can induce a response that is relatively resistant to host suppressor mechanisms. Evidence that they do so by activating contrasuppressor cells is discussed.