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PubMedDate not supplied

Regulation of immunity to extraembryonic antigens in human pregnancy.

Pregnancy results in the immunologic challenge of the female to a wide variety of allogeneic antigens. Particular attention has been given to antibodies directed to allotypic trophoblast antigens (TLX), for trophoblast form the true allograft interface between mother and fetus. Studies found that antibodies to paternal TLX allotypes are produced in women suffering from secondary recurrent abortions. These TLX antibodies are not directed to classical HLA private epitopes. In this report, treatment of lymphocytes with papain to remove HLA Class I did not decrease TLX antigen densities. These results suggest TLX antibodies are not directed to Class I epitopes, public or private. The allotypic nature of TLX antigens requires that a pregnant female must be able to regulate TLX immune responses to avoid rejection of the conceptus. One mechanism to specifically and systemically regulate TLX immunity is the idiotype anti-idiotype network. We provide preliminary evidence in this report for the presence of TLX idiotype network in a normal primigravida. Initially, no antipaternal TLX antibodies were detected in the serum of the primigravida, suggesting no TLX immunization had occurred. However, separation of Ab1 from Ab2 by absorption of primigravida serum with 2 degrees aborter Ab1 resulted in seroconversion. The primigravida's Ab1 was cytotoxic for paternal and 3rd-party lymphocytes in a non-HLA-restricted pattern. Primigravida's Ab2 was recovered from the Ab1 matrix by competitive elution by using platelets as source of TLX antigen. The Ab2 was found to inhibit cytotoxicity by 2 degrees aborter Ab1 as well as primigravida Ab1. This is evidence that the Ab2 recognizes a cross-reactive idiotype (CRI) on TLX antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Anti-Idiotypic↗
PubMed1987

Antigens of human trophoblast: trophoblast-lymphocyte cross-reactive antigens on platelets.

Human and rabbit antibodies to trophoblast-lymphocyte cross-reactive (TLX) antigens were employed in an enzyme-linked immunosorbent assay (ELISA) to identify and characterize the TLX alloantigen system on human platelets. Neither washing nor extraction in chaotrope or acid altered platelet TLX. The antigen was significantly changed by pronase and trypsin digestion, but Folch extraction yielded antigen in the hydrophilic interface, suggesting carbohydrate. Rabbit antibodies prepared to HLA-negative human syncytiotrophoblast TLX antigens were shown by platelet ELISA to have the same specificity and similar allotypy as anti-TLX antibodies from secondary (2 degrees) spontaneously aborting women. Patients with normal pregnancies before becoming 2 degrees aborters had both IgG and IgM antibodies to TLX. Anti-TLX in patients who never had a normal pregnancy were predominantly IgG. ELISA reactions performed with different concentrations of protein in the buffers detected anti-TLX activity in buffers containing high protein concentrations. This has been observed in studies of blocking antibodies in graft-versus-host disease and immune responses to tumor cells. Platelet TLX offers a new genetic and immunological approach to study similarities of the host-parasite relationships in pregnancy, transplantation, and cancer.

Abortion, Habitual↗
PubMed2003

Expression of the transcription factor, tailless, is required for formation of superficial cortical layers.

The gene tailless (tlx) encodes a forebrain-restricted transcription factor that is robustly expressed in progenitor cells of the ventricular and subventricular zones during neurogenesis. To investigate the role of tlx in neocortical development we generated a targeted deletion of tlx by homologous recombination. Here we compared the lamination, connectivity and patterning of cortical regions in adult tlx-/- mice and their wild-type littermates. We found first that neocortical thickness is reduced by 20% in mutant animals; most of this reduction is due to a diminution of supragranular layers, while layer I and layers IV through VI are relatively intact cytoarchitecturally. Consistent with this, the cross-sectional area of the corpus callosum is reduced by over 40%. Second, thalamocortical and intrinsic excitatory circuits in tlx-/- mice exhibit an essentially normal distribution from layer IV to the white matter, but are reduced superficial to layer IV. Finally, within parietal cortex of mutant mice a vibrissa-like pattern of cortical barrels is present in the expected rostro-caudal location. These observations indicate that loss of tlx function most severely affects generation and differentiation of neurons destined for superficial cortical layers. Thus, tlx may be important in sustaining the progenitor cell population throughout late prenatal development. Establishment of functional cortical areas, and development of basic patterns of thalamocortical and intra-cortical circuits occurs independently of tlx function.

Agenesis of Corpus Callosum↗
PubMed1988

Trophoblast antigens in human seminal plasma.

Secondary recurrent spontaneous (2 degrees) aborters manifest persistent IgG, which show differential cytotoxicity patterns with lymphocytes from many donors. These are non-HLA-directed antibodies, which react allotypically with both trophoblast and lymphocytes. The antigens they recognize are designated trophoblast-lymphocyte crossreactive (TLX) antigens. Xenogeneic anti-TLX sera were studied with the use of enzyme-linked-immunosorbent (ELISA) and immunochemical assays to determine the TLX status of seminal plasma. The results showed 1) allotypic TLX antigens are present in seminal plasma; 2) seminal plasma TLX antigens may be membrane associated; 3) by immunoblotting, the molecular weights of antigens reactive with TLX antisera are 15, 22, 28, 33 kD and a smear between 180 and 340 kd; 4) by isoelectric focusing, TLX antigens show pI 4.0, 5.35, 5.9, 6.5, 6.8, and 7.2. Allotypic seminal plasma TLX antigens may provide the antigenic stimuli for persistent maternal humoral immunity.

Abortion, Habitual↗
PubMed1986

Trophoblast antigens in normal and abnormal human pregnancy.

With all of this information about trophoblast antigens, it is necessary to have a working hypothesis of how these antigens might be dealt with by a normal woman's immunologic system. Two sets of observations have helped formulate such a working hypothesis. First is the finding that trophoblast is the only normal tissue recognized by antibodies to TA1 (and it is exceedingly difficult to demonstrate maternal anti-TA1 in normal pregnancies). Second is the serologic result that antibodies to TLX antigens within the TA2 group are lymphocytotoxic (and maternal anti-TLX can be demonstrated both in normal and abnormal pregnancies). We interpret this as meaning that TA1 is "foreign" (i.e., oncoextraembryonic) antigen and TA2 (TLX) is "self"-antigen, and that mothers have TA2 (TLX) reactive B-lymphocytes in their repertoire. Antigen-reactive B-lymphocytes can be activated to produce TA1-blocking antibodies by either allotypic TA2 (TLX) in seminal plasma or allogeneic trophoblast membrane antigens during the host-versus-graft reaction subsequent to blastocyst implantation. If allotypic or allogeneic stimulation fails to produce an adequate anti-TA2 (TLX) response, the oncoextra-embryonic TA1 antigens are recognized and rapidly rejected. If allotypic or allogeneic stimulation produces an aberrant anti-TA2 (TLX) response (e.g., a cytotoxic rather than a blocking antibody), the extra-embryonic membranes and placenta come under immune attack and eventually are rejected. This working hypothesis has led us to develop new immunologic approaches to the diagnosis and prevention of some types of pregnancy failures in both mice and human beings.

Abortion, Habitual↗
PubMed1989

Immunological studies of trophoblast antigens: no evidence for human leucocyte antigen (HLA) linkage.

Parental disparity for trophoblast-lymphocyte crossreactive (TLX) antigens may promote successful pregnancy. A TLX antigen system has been defined on peripheral blood lymphocytes by heteroantisera. More recently, we have reported additional activity against antigens on B lymphocytes alone termed trophoblast-B lymphocyte crossreactive (TBX) antigens. In the present study we have investigated ten TLX sera in order to determine if their target antigens are linked to the human leucocyte antigen (HLA) gene complex. The sera showed no selective activity when tested against target B lymphocytes from ten normal donors. Cytotoxic activity of TLX antisera against peripheral blood lymphocytes from six normal donors was not reduced when the class I HLA antigens of the target cells were blocked with a monoclonal antibody (PA 2.6). Similarly the cytotoxic activity of both TBX antisera against B lymphocytes from six normal donors was not decreased when class II HLA antigens were blocked by a monoclonal antibody (FMC 4). Within a family the cytotoxic activity of the TLX antisera was absorbed equally by lymphocytes from siblings who shared neither HLA haplotype. Antibody content in TLX and TBX antisera is not directed toward the classically defined HLA class I or class II antigens and is not linked to the HLA gene complex.

Animals↗
PubMed2002

Loss of the tailless gene affects forebrain development and emotional behavior.

We are studying the role of the evolutionarily conserved tlx gene in forebrain development in mice. Tlx is expressed in the ventricular zone that gives rise to neurons and glia of the forebrain. We have shown by mutating the tlx gene in mice, that in the absence of this transcription factor, mutant animals survive, but suffer specific anatomical defects in the limbic system. Because of these developmentally induced structural changes, mice with a mutation in the tlx gene can function, but exhibit extreme behavioral pathology. Mice show heightened aggressiveness, excitability, and poor cognition. In this article, we present a summary of our findings on the cellular and behavioral changes in the forebrain of mutant animals. We show that absence of the tlx gene leads to abnormal proliferation and differentiation of progenitor cells (PCs) in the forebrain from embryonic day 9 (E9). These abnormalities lead to hypoplasia of superficial cortical layers and subsets of GABAergic interneurons in the neocortex. We examined the behavior of mutant animals in three tests for anxiety/fear: the open field, the elevated plus maze, and fear conditioning. Mutant animals are less anxious and less fearful when assessed in the elevated plus and open-field paradigm. In addition, mutant animals do not condition to either the tone or the context in the fear-conditioning paradigm. These animals, therefore, provide a genetic tool to delineate structure/function relationships in defined regions of the brain and decipher how their disruption leads to behavioral abnormalities.

Aggression↗
PubMedDate not supplied

Immune recognition at the maternal-fetal interface: overview.

Trophoblast antigens at the maternal-fetal interface that are capable of stimulating maternal immune responses have been studied. Candidates are blood group I and P, HLA, Fc gamma-receptors, TLX, and phospholipids. Antigens I and P on trophoblast have been implicated in pregnancy loss but incompatible i,p mothers are rare. HLA-G is expressed on cytotrophoblast; however, no evidence for HLA-G allotypy or maternal responses to these molecules exists, although HLA-G has been implicated in recruitment of suppressor T cells. Receptors for IgG (Fc gamma-RI, Fc gamma-RII and Fc gamma-III) are present on trophoblast but allotypy is limited to the NA1-NA2 antigen system associated with Fc gamma-RIII on neutrophils. Maternal Fc-gamma R blocking antibodies have been linked to pregnancy success. The TLX alloantigen system was described by using xenogeneic antisera. Idiotype-antiidiotype regulated maternal responses to TLX are proposed as necessary for successful pregnancy. Several putative TLX monoclonal antibodies (Mab) recognize a regulator of complement activation called MCP (membrane cofactor protein, or CD46). Mab to MCP do not exhibit allotypy. Syncytial and cytotrophoblastic membranes are rich sources of MCP. Preliminary data suggest that a conformational site induced by C3b (iC3) binding to MCP may be responsible for TLX allotypy. Certain pregnancy loss patients produce antiphospholipid antibodies (aPA). Some investigators believe that aPA recognize a plasma protein cofactor, beta 2 GPI and not phospholipid per se. We produced three Mab specific for beta 2 GPI, one of which fails to recognize beta 2 GPI bound to phospholipid [corrected].(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗
PubMed1989

Seminal vesicles: a source of trophoblast lymphocyte cross-reactive antigen.

Maternal recognition of allotypic trophoblast lymphocyte cross-reactive (TLX) antigens is proposed to be involved in immunologic acceptance of the allogeneic fetus. The presence of TLX antigens in seminal plasma suggests that sensitization can occur before fertilization and implantation. In this study, the origin of TLX antigens within the male reproductive tract was investigated. Analysis of split ejaculates and immunohistological examinations of male accessory gland tissues showed the luminal epithelium of seminal vesicles as the source of seminal plasma TLX antigens. This finding suggests that seminal vesicles may play a role in the immunology of human reproduction.

Animals↗
PubMed1991

Trophoblast immunity in human pregnancy defined by antiidiotype.

Successful reproduction in mammals requires the mother to immunologically accept genetically disparate tissues. Allotypic trophoblast antigens (TLX) are thought to be responsible for influencing maternal acceptance of the feto-placental graft, and faulty regulation of immunity to TLX antigens has been associated with recurrent pregnancy losses. In this report, rabbit antiidiotype (RAb2) was produced to a human TLX antibody (Ab1). This RAb2 detected TLX cross-reactive idiotypes (CRI) on antitrophoblast IgG from women with normal and abnormal pregnancies. These findings support an hypothesis that women respond immunologically to allotypic trophoblast antigens, and that idiotype-antiidiotype regulation of this response is characteristic of normal pregnancy.

Abortion, Spontaneous↗
PubMed2004

Mental workload in air traffic control: an index constructed from field tests.

BACKGROUND: Mental workload assessment is a recurrent issue in air traffic control (ATC). Studies of ATC have used either objective aspects, i.e., numbers and distribution of aircraft, or subjective factors, such as self-imposed performance and stress levels, with mixed results. This is partly due to the difficulty in bringing together comparable data pertaining to both air traffic, with its ever-changing distribution, and judgement or quickly fluctuating psychophysiological variables. METHODS: We propose a method of mental load estimation devised to take into account both objective traffic variables and the additional load imposed by subjective effects, including the seriousness of conflicts and the time-pressure for their resolution. First, we developed a traffic load index (TLI) to identify time boundaries during which additional load may occur. Then we quantified the additional load according to the air traffic situation. RESULTS: TLI was developed from analysis of 25 h of recordings of radar control sessions involving 25 professional air traffic controllers at a major airport. Results were then compared with a simple objective index (number of aircraft) and subjective workload ratings (NASA-TLX test). The whole population (intersubjects analysis) showed a better correlation between the TLI and the self-rated workload than for the number of aircraft alone. Among the controllers who rated more than one level of workload through the TLX-test, 77.8% showed better correlation between TLI and TLX than between N and TLX (intrasubjects analysis). CONCLUSION: Workload estimation should integrate both objective task variables and subjective evaluations associated with them.

Accidents, Aviation↗
PubMed2005

[The appraisal of reliability and validity of subjective workload assessment technique and NASA-task load index].

OBJECTIVE: To test the reliability and validity of two mental workload assessment scales, i.e. subjective workload assessment technique (SWAT) and NASA task load index (NASA-TLX). METHODS: One thousand two hundred and sixty-eight mental workers were sampled from various kinds of occupations, such as scientific research, education, administration and medicine, etc, with randomized cluster sampling. The re-test reliability, split-half reliability, Cronbach's alpha coefficient and correlation coefficients between item score and total score were adopted to test the reliability. The test of validity included structure validity. RESULTS: The re-test reliability coefficients of these two scales and their items were ranged from 0.516 to 0.753 (P < 0.01), indicating the two scales had good re-test reliability; the split-half reliability of SWAT was 0.645, and its Cronbach's alpha coefficient was more than 0.80, all the correlation coefficients between its items score and total score were more than 0.70; as for NASA-TLX, both the split-half reliability and Cronbach's alpha coefficient were more than 0.80, the correlation coefficients between its items score and total score were all more than 0.60 (P < 0.01) except the item of performance. Both scales had good inner consistency. The Pearson correlation coefficient between the two scales was 0.492 (P < 0.01), implying the results of the two scales had good consistency. Factor analysis showed that the two scales had good structure validity. CONCLUSION: Both SWAT and NASA-TLX have good reliability and validity and may be used as a valid tool to assess mental workload in China after being revised properly.

Adolescent↗
PubMed2006

Measurement of the clinical usability of a configurable EHR.

The objective of the project was to measure the clinical usability of an EHR configured by use of participatory design with clinicians from a neurological stroke unit in order to get input to the County's future strategy for incremental implementation of EHR. The content of the EHR was defined during a series of workshops with the clinicians after which the XML configuration files were written and deployed. In parallel with this, the participants from the University identified, prioritised and further specified a number of effects related to the clinical practice to be measured. The effects requested by the clinicians focused on improving their overview and assessment of patients as well as on more efficient coordination in three specific and highly cooperative situations, viz. nursing handover, ward round and patient conference. All three situations were measured before (using paper-based medical records) as well as during the week where the configured EHR completely replaced the paper-based medical record in order to compare a 'before' and 'after' situation. Measurements were focused on the requested effects and acquired using various techniques including questionnaires, interviews, observations, and Task Load Index (TLX) ratings. In total, 15 nursing handovers, 8 ward rounds, and 11 patient conferences involving a total of 35 patients and more than 20 clinicians were included in the measurements. Data from the project has been comparatively analysed by means of the TLX scores. Our results show several significant results, for example, during ward rounds the physicians experienced a significant improvement of TLX. The experiment has proven it possible to configure the content of an EHR that significantly improves the clinician's overview of the patient's current status in different clinical situations during the clinical process, based on the clinician's actual needs. Furthermore, the configuration process gave the County valuable experience concerning the content and management of a participatory design process as well as documentation of utility value that will be incorporated in future EHR projects.

Denmark↗
PubMed1983

Changes in anatomical distribution of tumour lesions induced by platelet-active drugs.

To examine the effect of platelet-active drugs on the spread of blood-borne tumour cells, two murine tumours, sarcoma 180 (S-180) and TLX-5 lymphoma, were selected. Following intravenous (IV) injection into CBA mice the former elicited thrombocytopenia and formed discrete pulmonary tumours, whereas the latter failed to elicit thrombocytopenia and formed discrete tumours in all visceral organs examined except the lungs. S-180 cells were injected IV into mice pre-treated with RA233 (known to prevent thrombocytopenia and thrombus formation) and TLX-5 cells were injected IV into mice pre-treated with Corynebacterium parvum (known to induce thrombocytopenia and thrombus formation). RA233 pre-treatment did not change survival time or incidence of S-180 pulmonary tumours but did result in a higher incidence of extrapulmonary tumours and a lower tumour cell burden immediately after injection. Pre-treatment with C. parvum resulted in a higher TLX-5 tumour cell burden but not discrete tumours in the lungs. On the basis of known drug activities it is proposed that thrombocytopenia induced in these experiments is in part a reflection of thrombus formation in the lungs which influences the speed of passage of tumour cells through capillaries. In some cases this may lead to a changed anatomical distribution of tumour lesions.

Animals↗
PubMed2001

Expression of zTlxA, a Hox11-like gene, in early differentiating embryonic neurons and cranial sensory ganglia of the zebrafish embryo.

We have isolated a cDNA encoding a member of the Tlx/Hox11 family of homeodomain factors from the zebrafish, most closely related to the vertebrate Tlx-1/Hox11 and Tlx-3/Hox11L2 proteins. The gene is expressed in a set of early differentiating neurons that project to a common tract, the lateral longitudinal fascicle. We show that the gene is specifically expressed in spinal cord Rohon Beard neurons, in nucleus of the posterior commissure neurons of the midbrain, in a set of hindbrain neurons that include RoL3 reticulospinal interneurons, and in the trigeminal, statoacoustic, anterior lateral line, glossopharyngeal, and vagal cranial sensory ganglia. Timing of expression of the gene in these neurons correlates with the phase of axonal outgrowth and target innervation. Expression of the gene is also observed in several non-neural tissues, including the pharyngeal arches, budding gill filaments, outgrowing semicircular protrusions in the otic vesicle, and in the pectoral fin buds.

Amino Acid Sequence↗
PubMed1990

Localization and characterization of the acrosomal antigen recognized by GB24 on human spermatozoa.

GB24, a mouse monoclonal antibody, recognizes a trophoblast-leukocyte cross-reactive antigen (TLX), which is likely identical to the membrane cofactor protein (MCP), a complement regulatory protein. GB24 reacts also with a human acrosomal sperm antigen (Fénichel et al.: J Reprod Fertil 87:699-706, 1989). By immunofluorescence or immunoperoxidase, testicular, epididymal, and ejaculated spermatozoa were found to be positive after fixation by acetone. Motile, suspended spermatozoa became positive only through conditions known to induce acrosome reaction (A23187, follicular fluid, contact with oocytes). Ultrastructural studies with immunogold staining localized this protein on the inner acrosome membrane and in the acrosomal content. By SDS-polyacrylamide gel electrophoresis, GB24 immunoprecipitated a unique protein of 48 kDa from capacitated and A23187-induced spermatozoa under reducing conditions. No cross-reactivity was found with mouse, boar, or ram spermatozoa. Localization of this human sperm antigen recognized by GB24 and its similarity with the TLX-MCP family antigens would suggest a possible role of this molecule during fertilization in sperm-egg binding or immune protection.

Acrosome↗
PubMed2006

Construct and face validity and task workload for laparoscopic camera navigation: virtual reality versus videotrainer systems at the SAGES Learning Center.

BACKGROUND: Laparoscopic camera navigation (LCN) training on simulators has demonstrated transferability to actual operations, but no comparative data exist. The objective of this study was to compare the construct and face validity, as well as workload, of two previously validated virtual reality (VR) and videotrainer (VT) systems. METHODS: Attendees (n = 90) of the SAGES 2005 Learning Center performed two repetitions on both VR (EndoTower) and VT (Tulane Trainer) LCN systems using 30 degrees laparoscopes and completed a questionnaire regarding demographics, simulator characteristics, and task workload. Construct validity was determined by comparing the performance scores of subjects with various levels of experience according to five parameters and face validity according to eight. The validated NASA-TLX questionnaire that rates the mental, physical, and temporal demand of a task as well as the performance, effort, and frustration of the subject was used for workload measurement. RESULTS: Construct validity was demonstrated for both simulators according to the number of basic laparoscopic cases (p = 0.005), number of advanced cases (p < 0.001), and frequency of angled scope use (p < 0.001), and only for VT according to training level (p < 0.001) and fellowship training (p = 0.008). Face validity ratings on a 1-20 scale averaged 15.4 +/- 3 for VR vs. 16 +/- 2.6 for VT (p = 0.04). Ninety-six percent of participants rated both simulators as valid educational tools. The NASA-TLX overall workload score was 69.5 +/- 24 for VR vs. 68.8 +/- 20.5 for VT (p = 0.31). CONCLUSIONS: This is the largest study to date that compares two validated LCN simulators. While subtle differences exist, both VR and VT simulators demonstrated excellent construct validity, good face validity, and acceptable workload parameters. These systems thus represent useful training devices and should be widely used to improve surgical performance.

Adult↗