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PubMed1993

Order effects and the weighting process in workload assessment.

Operators controlling a power grid were subjects in a mental workload experiment in which they performed their normal tasks under simulated quiet and busy conditions. Workload was assessed using the NASA Task-Load Index (TLX). It was found that there were significant differences between the two conditions, but there were no order effects. The value of the weighting procedure was assessed by correlating unweighted and weighted workload ratings. Although the correlations were high, they were not perfect, indicating some value for weighting the dimensions of the TLX. Large individual differences were observed in perceived workload.

Journal Article↗
PubMed1995

Immunogenetic study of couples with recurrent spontaneous abortions.

OBJECTIVES: Clinical observations suggest that genetic and immunologic disparity could be a factor in fecundity. The HLA system (HLA) is polymorphic and TLX (Trophoblast Lymphocyte Cross-Reactive), which is also polymorphic, seems to be linked to it. The immunologic hypothesis follows that excessive HLA and TLX-sharing could explain the rejection of a semi-allogenic blastocyst. Study objectives are therefore twofold; To determine whether or not there is significant HLA-sharing between spouses with unexplained recurrent spontaneous abortions (RSA) and to determine whether or not there is an association between some HLA specificities and RSA. STUDY DESIGN: The study includes only Caucasian couples that have had three successive spontaneous abortions. These were distributed in two groups: Group E: 18 couples either with known aetiology or with secondary RSA; Group U: seven couples with unexplained primary RSA; Control group C: 21 couples with at least two children and no spontaneous abortions. Tissue typing for HLA-A and B molecules was performed using serotyping methodology based on lymphocytotoxicity reaction. The different DRB1 alleles (class II) were determined by oligotyping with a non-radioactive reverse dot-blot methodology. RESULTS: Statistical comparison shows that the number of couples without shared specificity is not significantly different between the three groups for each locus independently and for the set of three. Our results show also that the allelic frequencies are not significantly different between the three groups. CONCLUSIONS: There is no higher HLA-sharing in couples with RSA than in fertile couples. Similarly, no particular HLA specificity can be associated with the RSA.

Abortion, Habitual↗
PubMed1991

Small angle x-ray diffraction studies on the topography of cannabinoids in synaptic plasma membranes.

In a previous publication, we have described in detail how we used small angle x-ray diffraction to determine the topography of (-)-delta 8-tetrahydrocannabinol (delta 8-THC) in dimyristoylphosphatidylcholine (DMPC) bilayers, and to deduce the conformation of the THC side chain by using the iodo-analog (5'-I-delta 8-THC) in the model membrane. We have now extended our studies to synaptic plasma membrane systems where the cannabinoids are believed to exert part of their pharmacological effects. Synaptic plasma membranes (SPM) were isolated from fresh bovine brains and delta 8-THC was incorporated into the membranes. By comparing the electron density profiles of drug free and drug-containing SPM preparations, we observed an electron density increase due to the presence of delta 8-THC in a region centered at 9.2 A from the terminal methyl groups of the membrane bilayer. In an attempt to dissect the effects of different membrane components on the topography of delta 8-THC, we carried out parallel experiments using membrane preparations from the synaptosomal membrane total lipid extract (TLX) as well as from bovine brain phosphatidyl choline extract (PCX) containing 30 mole percent cholesterol (Chol). Our results regarding the topography of delta 8-THC and 5'-I-delta 8-THC in these lipid membranes show that the TLX bilayer simulates the natural membrane environment very closely whereas in the PCX/Chol bilayer delta 8-THC resides at a location approximately 4 A closer to the membrane interface, similar to that found in our previous study using DMPC model membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Psychophysiological responses to changes in workload during simulated air traffic control.

In this investigation, eight Air Force air traffic controllers (ATCs) performed three scenarios on TRACON (Terminal Radar Approach Control), a computer-based air traffic control (ATC) simulation. Two scenarios were used each with three levels of difficulty. One scenario varied traffic volume by manipulating the number of aircraft to be handled and the second scenario varied traffic complexity by manipulating arriving to departing flight ratios, pilot skill and mixture of aircraft types. A third scenario, overload, required subjects to handle a larger number of aircraft in a limited amount of time. The effects of the manipulations on controller workload were assessed using performance, subjective (TLX), and physiological (EEG, eye blink, heart rate, respiration, saccade) measures. Significant main effects of difficulty level were found for TRACON performance, TLX, eye blink, respiration and EEG measures. Only the EEG was associated with main effects for the type of traffic. The results provide support for the differential sensitivity of a variety of workload measures in complex tasks, underscore the importance of traffic complexity in ATC workload, and support the utility of TRACON as a tool for studies of ATC workload.

Adult↗
PubMed2005

Abnormal development of zinc-containing cortical circuits in the absence of the transcription factor Tailless.

Absence of the transcription factor tailless (tlx) leads to premature laminar development and thinning of neocortex. We used zinc autometallography to determine if tailless deletion alters the organization of cortical circuits. In tlx-/- mice, layer 4 barrels, which normally lack synaptic zinc, are densely innervated by zinc-containing terminals. Furthermore, barrels with zinc inputs are constructed, in part, from zinc-sequestering neurons, a phenotype not normally found in layer 4.

Animals↗
PubMed2000

Rnx deficiency results in congenital central hypoventilation.

The genes Tlx1 (Hox11), Enx (Hox11L2, Tlx-2) and Rnx (Hox11L2, Tlx-3) constitute a family of orphan homeobox genes. In situ hybridization has revealed considerable overlap in their expression within the nervous system, but Rnx is singularly expressed in the developing dorsal and ventral region of the medulla oblongata. Tlx1-deficient and Enx-deficient mice display phenotypes in tissues where the mutated gene is singularly expressed, resulting in asplenogenesis and hyperganglionic megacolon, respectively. To determine the developmental role of Rnx, we disrupted the locus in mouse embryonic stem (ES) cells. Rnx deficient mice developed to term, but all died within 24 hours after birth from a central respiratory failure. The electromyographic activity of intercostal muscles coupled with the C4 ventral root activity assessed in a medulla-spinal cord preparation revealed a high respiratory rate with short inspiratory duration and frequent apnea. Furthermore, a coordinate pattern existed between the abnormal activity of inspiratory neurons in the ventrolateral medulla and C4 motorneuron output, indicating a central respiratory defect in Rnx mice. Thus, Rnx is critical for the development of the ventral medullary respiratory centre and its deficiency results in a syndrome resembling congenital central hypoventilation.

Abnormalities, Multiple↗
PubMed1982

Effect of liposomally trapped antitumour drugs on a drug-resistant mouse lymphoma in vivo.

A TLX-5 mouse lymphoma which was resistant to 1-β-D-arabinofuranosyl cytosine (AraC) was used in vivo to study the possibility of using liposomes as drug-delivery vehicles in order to overcome drug resistance.The effects of free drugs (AraC, AraCTP and methotrexate) and the liposomally associated drugs on the survival time of tumour-bearing mice were determined.As a more sensitive measure of cell survival, (125)IUdR was incorporated into the DNA of the ascites TLX-5 cells before i.p. injection. Cell survival and the cytotoxic effects of the drugs on the tumour cells were determined by using a double-headed gamma counter to measure the retention of the (125)I label.Both AraC and AraCTP, either as the free drugs or liposomally associated, had no effects on the tumour. Due to the lack of response of tumour cells to these drugs, further studies were initiated with free and liposomally associated methotrexate (MTX), a drug to which the cells were known to be sensitive. It was found that the liposomally associated MTX, at a 5-10-fold lower dose than the free drug, was (a) more effective in prolonging the survival of tumour-bearing mice and (b) as effective as the free drug in killing tumour cells (as measured by the (125)I retention).In vivo MTX was more effective in the liposomally associated form, whereas liposomally entrapped AraC and AraCTP were ineffective. It is proposed that in vivo liposomally associated drugs may be acting not by actively localizing in the tumour cells, but by the liposomes providing a slow-release drug depot, improving the pharmacokinetic properties of MTX.

Animals↗
PubMed1988

The effect of tumour growth on liver pantothenate, CoA, and fatty acid synthetase activity in the mouse.

Enzymatic, and microbiological assays were used to determine the hepatic contents of coenzyme A, acetyl CoA, fatty acid synthetase activity, and pantothenate in livers of tumour-bearing mice. Significant decreases in CoA and acetyl CoA were found in mice bearing TLX-5 lymphoma, sarcoma 180 or a fibrosarcoma. These changes were accompanied by significant decreases in pantothenate and increases in 4-phosphopantothenate suggesting an increase in pantothenate kinase activity due to reduction of CoA inhibition of the enzyme. In contrast, large increases were found in pantothenate and 4-phosphopantothenate in mice bearing TLX-5 lymphoma, i.p. or s.c. These changes could be due to a large reduction in the rate of conversion of an intermediate in the pathway of CoA, or increased production of pantothenate or 4-phosphopantothenate from the degradation of CoA or the phosphopantetheine residue in fatty acid synthetase. Activities of fatty acid synthetase in liver of mice bearing this tumour showed marked decreases, but were insufficient to account for the increase in pantothenate, and may reflect a reduction in cytosolic CoA needed for the conversion of the apo to the holoenzyme.

Acetyl Coenzyme A↗
PubMed2004

Tlx3 and Tlx1 are post-mitotic selector genes determining glutamatergic over GABAergic cell fates.

Glutamatergic and GABAergic neurons mediate much of the excitatory and inhibitory neurotransmission, respectively, in the vertebrate nervous system. The process by which developing neurons select between these two cell fates is poorly understood. Here we show that the homeobox genes Tlx3 and Tlx1 determine excitatory over inhibitory cell fates in the mouse dorsal spinal cord. First, we found that Tlx3 was required for specification of, and expressed in, glutamatergic neurons. Both generic and region-specific glutamatergic markers, including VGLUT2 and the AMPA receptor Gria2, were absent in Tlx mutant dorsal horn. Second, spinal GABAergic markers were derepressed in Tlx mutants, including Pax2 that is necessary for GABAergic differentiation, Gad1/2 and Viaat that regulate GABA synthesis and transport, and the kainate receptors Grik2/3. Third, ectopic expression of Tlx3 was sufficient to suppress GABAergic differentiation and induce formation of glutamatergic neurons. Finally, excess GABA-mediated inhibition caused dysfunction of central respiratory circuits in Tlx3 mutant mice.

Amino Acid Transport Systems↗
PubMed1999

Identification of a photoreceptor cell-specific nuclear receptor.

Nuclear receptors comprise a large and expanding family of transcription factors involved in diverse aspects of animal physiology and development, the functions of which can be modulated in a spatial and temporal manner by access to small lipophilic ligands and/or the specificity of their own localized expression. Here we report the identification of a human nuclear receptor that reveals a unique proximal box (CNGCSG) in the DNA-binding domain. The conservation of this feature in its nematode counterpart suggests the requirement for this type of P box in the genetic cascades mediated by nuclear receptors in a wide variety of animal species. The expression of this receptor, PNR (photoreceptor-specific nuclear receptor), appears strongly restricted in the retina, exclusively in photoreceptor cells. In human cell lines, PNR expression was observed in Y79 retinoblastoma along with other photoreceptor marker genes such as CRX. Among vertebrate receptors, PNR shares structural kinship with an orphan receptor TLX, and despite distinct differences in the DNA binding domain, PNR is able to recognize a subset of TLX target sequences in vitro. Analyses of the human PNR gene revealed its chromosomal position as 15q24, a site that has recently been reported as a susceptible region for retinal degeneration. These data support a role for PNR in the regulation of signalling pathways intrinsic to the photoreceptor cell function.

Amino Acid Sequence↗
PubMed2003

A study on the student pilot's mental workload due to personality types of both instructor and student.

The main purpose of this paper is to provide the ideal flight crew combination for instructor and student pilots in order to enhance the flight training effects based on Myers Briggs Type Indicator (MBTI) theory. In addition to personality, various levels of flight difficulty are considered in order to investigate their potential interaction effect in terms of student pilots' mental workload measured in heart rate, altitude deviation, NASA-TLX (Task Load Index) and subjective degree of personality harmony. Based on an experiment performed in a real flight situation, we found significant effects of personality combinations in terms of all four outcome measures. Both group C types of instructors and students who are concrete, realistic and have mechanical skills turn out to be the ideal flight crew combination. A structural equation model, fitted to analyse causality among the four response variables, implied that as the heart rate increased, the altitude deviation increased. In addition, as the altitude deviation and personality harmony increased, NASA-TLX increased. The results of this study are expected to provide a theoretical basis for manning the flight crew combinations and thereby enhancing the efficiency of flight training.

Aviation↗
PubMed2005

Effect of air pollution on olfactory function in residents of Mexico City.

To our knowledge there has been no study of the effect of everyday air pollution on olfactory function. It was therefore the aim of this study to compare the olfactory performance of long-term residents of Mexico City, an environment with high air pollution, with the olfactory performance of residents of the Mexican state of Tlaxcala, a region geographically similar to Mexico City but with low air pollution. Healthy volunteers [82 Mexico City subjects (MEX), 86 Tlaxcala subjects (TLX)] 20-63 years of age and balanced for age and gender between the two localities were tested for the perception of the odors of everyday beverages presented in squeeze bottles. When tested with ascending concentrations of stimuli in a three-way oddball paradigm, residents of Tlaxcala detected the odors of instant coffee and of an orange drink at significantly lower concentrations than residents of Mexico City. They also performed significantly better in discriminating between the two similar-smelling Mexican beverages horchata and atole in an oddball test. Significant differences between the two populations in overall olfactory performance were apparent in three of the four age classes (20- to 29-, 30- to 39-, and 40- to 49-year-old subjects) but not in the 50-63 years age class. About 10% of MEX subjects compared to about 2% of TLX subjects were judged to have poor olfactory function; all were from the older age classes (mean age: 48.6 years). Thus, air pollution in Mexico City appears to have a substantial impact on olfactory function even in young and middle-aged residents.

Adult↗
PubMed1987

Reproductive immunology: biomarkers of compromised pregnancies.

The objective of this paper is to consider several categories of biomarkers of human pregnancy. The design of the report is to discuss useful and promising markers and techniques. Research gaps, needs, and priorities are also defined. Useful markers are mixed lymphocyte culture reactions, measures of lymphocytotoxic antibodies, histocompatibility (HLA) typing, and immunohematological evaluations. Promising markers are measures of major basic protein and early pregnancy factor, as well as determinations of trophoblast-lymphocyte cross-reactive (TLX) antigens. Promising techniques are fluorescence-activated cell-sorter analysis of maternal blood for fetal and extraembryonic tissues and immunotherapy with TLX and other antigens to prevent spontaneous abortion. It is concluded that immunology has much to offer the development of biomarkers of human pregnancy.

Antibodies↗
PubMed2003

Electroporation of proviral RCAS DNA alters gene expression in the embryonic chick hindbrain.

Gene transfer by means of electroporation is an effective method for delivering DNA into cells. Expression vectors encoding green fluorescent protein (GFP) are routinely used as a control for this technique and are also regularly used to indirectly or directly monitor the expression of introduced transgenes. However, recent studies suggest that GFP may have nonspecific and/or cytotoxic side effects. In this study, we investigated the effects of enhanced GFP (EGFP) expression delivered by means of electroporation of proviral RCASBP(B)-EGFP DNA on gene expression in the hindbrain of chick embryos. We examined, via whole-mount in situ hybridization, the expression of a number of transcription factors. We found that Tlx-1 was ectopically expressed following electroporation of proviral RCASBP(B)-EGFP DNA. In contrast, the number of cells expressing Tlx-3, Phox2a, and Phox2b were reduced. Intriguingly, these effects could be mimicked by electroporation of wild-type proviral RCASBP(B) DNA (i.e., lacking the GFP insert). However, neither delivery of the EGFP transgene by means of viral infection nor electroporation alone yielded aberrant expression patterns. Together our data indicate that alterations of gene expression patterns are not directly due to the expression of EGFP but instead reflect a confounding effect of electroporating proviral DNA.

Animals↗
PubMed1995

Dysregulation of HOX11 by chromosome translocations in T-cell acute lymphoblastic leukemia: a paradigm for homeobox gene involvement in human cancer.

The translocation t(10;14)(q24;q11) is observed in the course of routine cancer cytogenetic studies in 5-10% of patients with T-cell acute lymphoblastic leukemia (ALL). Recent molecular dissections of t(10;14) translocations support the hypothesis that these relatively gross chromosomal mutations represent key genetic steps in neoplastic transformation. The genes consistently involved are the T-cell receptor (TCR) delta-chain gene in 14q11 and a human homeobox-containing gene in 10q24, HOX11, initially identified through cloning of t(10;14) translocations. Like other homeoproteins, HOX11 binds DNA with sequence specificity and is likely to be a transcription factor, controlling the expression of developmentally important genes. The t(10;14) translocations arise as a result of aberrant physiological recombinational events that occur at early stages of T-cell development, probably during failed attempts at TCR gene rearrangement. The net result of the aberrant genetic recombinations is inappropriate expression of HOX11 in individual T-cells that acquire the mutation. Tlx-1, the murine homolog of HOX11, is expressed embryologically in the developing spleen and in structures derived from cranial neural crest cells and migratory paraxial mesoderm. Mice homozygously deleted for Tlx-1 are asplenic. Thus, HOX11 may be one of the first examples in mammals of a "master gene" acting as a regulatory switch controlling a downstream program of organ-specific cell growth and proliferation. Preliminary tumorigenicity assays suggest that HOX11 expression in hematopoietic cells most likely plays an immortalization role in neoplastic transformation.(ABSTRACT TRUNCATED AT 250 WORDS)

Genes, Homeobox↗
PubMed2003

Inflight workload assessment: comparison of subjective and physiological measurements.

INTRODUCTION: Assessment of pilot workload during flight is an important aviation safety consideration. The aim of this study was to assess inflight pilot workload using both physiological and multidimensional subjective-ratings measurements (heart rate and NASA Task Load Index, respectively), comparing relative sensitivity during the four phases of flight: take-off, cruise, approach, and landing. METHODS: Ten male pilots volunteered to participate in the trials, which took place in a Boeing 747-400 flight simulator. Electrocardiography was performed throughout the test using the portable Cardiovis ECG system. Mean heart rate (HR) and incremental heart rate (delta HR) were considered indices of physiological workload. RESULTS: Peak HR was observed during take-off (83.2 bpm) and landing (88.6 bpm); moreover, delta HR was also greatest (14.2 bpm and 18.8 bpm). The Task Load Index (TLX) scale revealed that mental and performance demands were essential components of workload during flight. In addition, temporal demand was an important component of workload during take-off and physical demand was significant during cruise. Analysis of correlation revealed that the delta HR is significantly related to TLX scores (r = 0.81, n = 40). CONCLUSIONS: Management of the individual sources of stress, which tend to become predominant during different flight phases, should be emphasized in periodic recurrent training. For example, a pilot must be trained to cope with the increased temporal stresses associated with take-off. In addition, the recommendations will be concerned with maintaining vigilance, task allocation between pilots, and inflight rest during long-haul cruise.

Adult↗
PubMed1988

[The place of immunology in recurring spontaneous abortion].

Spontaneous repeated miscarriages are often explained by an immunological mechanism. Whereas in normal pregnancy the mother develops a tolerance immune response induced by paternal antigens of fetus, she is unable to react in this variety of miscarriage. The immunological theory is supported by some solid experimental arguments, which are detailed. Antigens generating the tolerance response are probably TLX antigens, expressed on syncitiotrophoblast and cross reacting with class I HLA antigens. Diagnosis of immunological miscarriage is based on elimination of other causes and on absence in woman of antibodies directed against husband class I antigens. Tolerance immune response can be induced by injections to wife of great quantity of conjunct lymphocytes. An anti HLA, and later on anti TLX, immunization is often obtained. Several teams have applied this treatment, with frequent good results: about 80% of fecundated patients conduct a normal pregnancy until its time.

Abortion, Habitual↗
PubMedDate not supplied

[Prevention of habitual abortion by buffycoat transfusions].

From an immunological point of view the product of pregnancy may be regarded as a haplo-different allotransplant. A system possibly closely linked to the HLA-region is postulated to lead to the immunological recognition of the fetus by the mother and, paradoxically, to a take of the "transplant". The postulated system apparently codes for antigens present on both trophoblast and adult lymphocytes (TLX = trophoblast-lymphocyte-crossreacting). The prevention of rejection is thought to be effected by blocking factors (BF) present in the serum or plasma of the mother. There may be different kinds of BF: a specific BF (detectable only in an autologous assay system), appearing late in pregnancy, which inhibits several lymphocyte-dependent reactions (e.g. production of MIF, MLC). This BF has been identified as an IgG-class antibody. a nonspecific BF, appearing early in pregnancy which inhibits the MLC in vitro. c) may be a third BF, also specific, which is found only in plasma but not in serum. All described BF-activities were absent in women with habitual abortions. HLA-identity or partial identity could imply TLX-identity. The consequence of such an identity could be: non-detection of the trophoblast by the immune system of the mother, no production of BF, abortion. However several investigators could not find any HLA-identity of the partners with habitual abortions. A protective effect on the fetus has been seen when pregnant women were immunised with adult leukocytes, using either buffycoats from various HLA-different but bloodgroup-compatible donors or isolated leukocytes from the spouse.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Habitual↗