ABSTRACT
Azadirachtin, a neem compound (Azadirachta indica) with medical and anti-insect properties, is one the most successful botanical pesticides in agricultural use. However, its controversial impact on non-targeted species and its mechanism of action need to be clarified. In addition, Azadirachtin impact on pre- and post-mating traits remains largely undocumented. The current study examined the effects of Azadirachtin on Drosophila melanogaster as a non-target and model species. Azadirachtin was applied topically at its LD50 (0.63µg) on the day of adult emergence and its effect was evaluated on several traits of reproductive behavior: mate choice, male activity, female sexual receptivity, sperm storage and female sterility. In choice and no choice conditions, only male treatment reduced mating probability. Female treatment impaired mating probability only when males had the choice. Males' mating ability may have been impaired by an effect of the treatment on their mobility. Such an effect was observed in the actimeter, which revealed that treated males were less active than untreated ones, and this effect persisted over 8days. Azadirachtin treatment had, however, no effect on the nycthemeral rhythm of those males. Even when mating occurred, Azadirachtin treatment impaired post-mating responses especially when females or both sexes were treated: remating probability increases and female fertility (presence of larvae) decreases. No impairment was observed on the efficiency of mating, evaluated by the presence of sperm in the spermatheca or the ventral receptacle. Male treatment only had no significant effect on these post-mating responses. These findings provide clear evidence that Azadirachtin alters the reproductive behavior of both sexes in D. melanogaster via mating and post-mating processes.
Subject(s)
Drosophila melanogaster/drug effects , Insecticides/toxicity , Limonins/toxicity , Sexual Behavior/drug effects , Animals , Drosophila melanogaster/physiology , Female , MaleABSTRACT
Voltage-gated Ca2+ channels are key transducers of cellular excitability and participate in several crucial physiological responses. In vertebrates, 10 Ca2+ channel genes, grouped in 3 families (CaV1, CaV2 and CaV3), have been described and characterized. Insects possess only one member of each family. These genes have been isolated in a limited number of species and very few have been characterized although, in addition to their crucial role, they may represent a collateral target for neurotoxic insecticides. We have isolated the 3 genes coding for the 3 Ca2+ channels expressed in Apis mellifera. This work provides the first detailed characterization of the honeybee T-type CaV3 Ca2+ channel and demonstrates the low toxicity of inhibiting this channel. Comparing Ca2+ currents recorded in bee neurons and myocytes with Ca2+ currents recorded in Xenopus oocytes expressing the honeybee CaV3 gene suggests native expression in bee muscle cells only. High-voltage activated Ca2+ channels could be recorded in the somata of different cultured bee neurons. These functional data were confirmed by in situ hybridization, immunolocalization and in vivo analysis of the effects of a CaV3 inhibitor. The biophysical and pharmacological characterization and the tissue distribution of CaV3 suggest a role in honeybee muscle function.
Subject(s)
Bees/drug effects , Bees/physiology , Calcium Channel Blockers/pharmacology , Calcium Channels, T-Type/metabolism , Locomotion/drug effects , Animals , Calcium Channels, T-Type/genetics , Gene Expression , Mibefradil/pharmacology , Neurons/drug effects , Neurons/metabolism , Olfactory Bulb/drug effects , Olfactory Bulb/physiology , Oocytes/drug effects , Oocytes/metabolism , XenopusABSTRACT
A previous nonblinded, randomized, single-center renal transplantation trial of single-dose rabbit anti-thymocyte globulin induction (SD-rATG) showed improved efficacy compared with conventional divided-dose (DD-rATG) administration. The present multicenter, double-blind/double-dummy STAT trial (Single dose vs. Traditional Administration of Thymoglobulin) evaluated SD-rATG versus DD-rATG induction for noninferiority in early (7-day) safety and tolerability. Ninety-five patients (randomized 1:1) received 6 mg/kg SD-rATG or 1.5 mg/kg/dose DD-rATG, with tacrolimus-mycophenolate maintenance immunosuppression. The primary end point was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary end points included 12-month patient survival, graft survival, and rejection. Target enrollment was 165 patients with an interim analysis scheduled after 80 patients. Interim analysis showed primary end point noninferiority of SD-rATG induction (p = 0.6), and a conditional probability of <1.73% of continued enrollment producing a significant difference (futility analysis), leading to early trial termination. Final analysis (95 patients) showed no differences in occurrence of primary end point events (p = 0.58) or patients with no, one, or more than one event (p = 0.81), or rejection, graft, or patient survival (p = 0.78, 0.47, and 0.35, respectively). In this rigorously blinded trial in adult renal transplantation, we have shown SD-rATG induction to be noninferior to DD-rATG induction in early tolerability and equivalent in 12-month safety. (Clinical Trials.gov #NCT00906204.).
Subject(s)
Antilymphocyte Serum/administration & dosage , Graft Rejection/drug therapy , Graft Survival/drug effects , Immunosuppressive Agents/administration & dosage , Kidney Transplantation/adverse effects , Adult , Animals , Double-Blind Method , Female , Glomerular Filtration Rate , Graft Rejection/etiology , Humans , Male , Middle Aged , Prospective Studies , Rabbits , Treatment OutcomeABSTRACT
This work presents a planar, longitudinal mode ultrasonic scalpel microfabricated from monocrystalline silicon wafers. Silicon was selected as the material for the ultrasonic horn due to its high speed of sound and thermal conductivity as well as its low density compared to commonly used titanium based alloys. Combined with a relatively high Young's modulus, a lighter, more efficient design for the ultrasonic scalpel can be implemented which, due to silicon batch manufacturing, can be fabricated at a lower cost. Transverse displacement of the piezoelectric actuators is coupled into the planar silicon structure and amplified by its horn-like geometry. Using finite element modeling and experimental displacement and velocity data as well as cutting tests, key design parameters have been identified that directly influence the power efficiency and robustness of the device as well as its ease of controllability when driven in resonance. Designs in which the full- and half-wave transverse modes of the transducer are matched or not matched to the natural frequencies of the piezoelectric actuators have been evaluated. The performance of the Si micromachined scalpels has been found to be comparable to existing commercial titanium based ultrasonic scalpels used in surgical operations for efficient dissection of tissue as well as coaptation and coagulation of tissue for hemostasis. Tip displacements (peak-to-peak) of the scalpels in the range of 10-50 µm with velocities ranging from 4 to 11 m/s have been achieved. The frequency of operation is in the range of 50-100 kHz depending on the transverse operating mode and the length of the scalpel. The cutting ability of the micromachined scalpels has been successfully demonstrated on chicken tissue.
Subject(s)
Dissection/instrumentation , Silicon/chemistry , Surgical Instruments , Ultrasonics/instrumentation , Animals , Chickens , Electric Impedance , Equipment Design , Finite Element Analysis , Hemostasis , Materials Testing , Reproducibility of Results , Swine , TransducersABSTRACT
Brain activity is inherently combinatorial and three-dimensional. Optical imaging techniques offer a suitable opportunity to record many activity foci simultaneously, but under conventional microscopy conditions, optical access is generally limited to the frontal part of the brain. Thus, even for cases in which optical recordings have delivered substantial data, our knowledge of deeper layers is deficient. Using the honeybee olfactory system as a test system, we report that by using a gold-sputtered cover slip as a minute mirror, it is possible to optically access and record from otherwise inaccessible brain areas. In insects, the first brain area to code for odors is the antennal lobe (comparable to the vertebrate olfactory bulb). Several previous studies have characterized glomerular odor response patterns of the frontal view, readily accessible when the head capsule of the bee is opened. However, until now, the back and the sides of the antennal lobe have remained utterly unexplored. This is particularly relevant because in the honeybee these two views coincide with two separate olfactory subsystems, related to two axonal tracts of second-order neurons: the lAPT and the mAPT. Combining wide-field microscopy, calcium imaging, and a minute mirror, we report the first glomerular odor responses from the side of the honeybee antennal lobe.
Subject(s)
Bees/physiology , Brain/physiology , Neuroimaging , Olfactory Perception/physiology , Animals , Organic ChemicalsABSTRACT
The antennal lobe (AL) is the first olfactory center of the insect brain and is constituted of different functional units, the glomeruli. In the AL, odors are coded as spatiotemporal patterns of glomerular activity. In honeybees, olfactory learning during early adulthood modifies neural activity in the AL on a long-term scale and also enhances later memory retention. By means of behavioral experiments, we first verified that olfactory learning between the fifth and eighth day of adulthood induces better retention performances at a late adult stage than the same experience acquired before or after this period. We checked that the specificity of memory for the odorants used was improved. We then studied whether such early olfactory learning also induces long-term structural changes in the AL consistent with the formation of long-term olfactory memories. We also measured the volume of 15 identified glomeruli in the ALs of 17-day-old honeybees that either experienced an odor associated with sucrose solution between the fifth and eighth day of adulthood or were left untreated. We found that early olfactory experience induces glomerulus-selective increases in volume that were specific to the learned odor. By comparing our volumetric measures with calcium-imaging recordings from a previous study, performed in 17-day-old bees subjected to the same treatment and experimental conditions, we found that glomeruli that showed structural changes after early learning were those that exhibited a significant increase in neural activity. Our results make evident a correlation between structural and functional changes in the AL following early olfactory learning.
Subject(s)
Bees/growth & development , Learning/physiology , Odorants , Olfactory Pathways/growth & development , Olfactory Perception/physiology , Animals , Animals, Newborn , Arthropod Antennae/growth & development , Brain/growth & development , InsectaABSTRACT
In the antennal lobe (AL), the first olfactory centre of the insect brain, odorants are represented as spatiotemporal patterns of glomerular activity. Whether and how such patterns are modified in the long term after precocious olfactory experiences (i.e. in the first days of adulthood) remains unknown. To address this question, we used in vivo optical imaging of calcium activity in the antennal lobe of 17-day-old honeybees which either experienced an odorant associated with sucrose solution 5-8 days after emergence or were left untreated. In both cases, we imaged neural responses to the learned odor and to three novel odors varying in functional group and carbon-chain length. Two different odor concentrations were used. We also measured behavioral responses of 17-day-old honeybees, treated and untreated, to these stimuli. We show that precocious olfactory experience increased general odor-induced activity and the number of activated glomeruli in the adult AL, but also affected qualitative odor representations, which appeared shifted in the neural space of treated animals relative to control animals. Such effects were not limited to the experienced odor, but were generalized to other perceptually similar odors. A similar trend was found in behavioral experiments, in which increased responses to the learned odor extended to perceptually similar odors in treated bees. Our results show that early olfactory experiences have long-lasting effects, reflected in behavioral responses to odorants and concomitant neural activity in the adult olfactory system.
Subject(s)
Association Learning/physiology , Odorants , Sense Organs/cytology , Sensory Receptor Cells/physiology , Smell/physiology , Social Behavior , Animals , Bees , Behavior, Animal , Brain Mapping , Calcium/metabolism , Calcium Signaling , Conditioning, Classical , Olfactory Pathways/physiology , Sensory Receptor Cells/drug effects , Statistics as TopicABSTRACT
In the honeybee, the conditioning of the proboscis extension response using tactile antennal stimulations is well suited for studying the side-specificity of learning including the possible bilateral transfer of memory traces in the brain, and the role of inhibitory networks. A tactile stimulus was presented to one antenna in association with a sucrose reward to the proboscis. The other antenna was either not stimulated (A+/0 training), stimulated with a non-reinforced tactile stimulus B (A+/B- training) or stimulated with B reinforced with sucrose to the proboscis (A+/B+ training). Memory tests performed 3 and 24h after training showed in all situations that a tactile stimulus learnt on one side was only retrieved ipsilaterally, indicating no bilateral transfer of information. In all these groups, we investigated the effect of the phenylpyrazole insecticide fipronil by applying a sublethal dose (0.5 ng/bee) on the thorax 15 min before training. This treatment decreased acquisition success and the subsequent memory performances were lowered but the distribution of responses to the tactile stimuli between sides was not affected. These results underline the role of the inhibitory networks targeted by fipronil on tactile learning and memory processes.
Subject(s)
Bees/drug effects , Bees/physiology , Insecticides/pharmacology , Pyrazoles/pharmacology , Animal Structures/drug effects , Animal Structures/physiology , Animals , Behavior, Animal/drug effectsABSTRACT
The importance of olfactory learning in host plant selection is well demonstrated in insects, including the heliothine moths. In the present study olfactory conditioning of the proboscis extension response was performed to determine the moths' ability to learn and discriminate three plant odorants: beta-ocimene and beta-myrcene (activating the same receptor neurone type), and racemic linalool (activating two different types). The conditioned stimulus (CS) was an air puff with each odorant blown into a constant air stream and over the antennae, and the unconditioned stimulus (US) was sucrose solution applied first to the antennal taste sensilla, then to the proboscis. Conditioning with increasing odorant concentrations induced increased learning performance. The concentration threshold for learning was 100 times lower for racemic linalool than for the two other odorants, a fact that can be correlated with a higher sensitivity of the moths' antennae to racemic linalool as shown in electroantennogram recordings. After correcting for the different odour sensitivities, the moths' ability to discriminate the odorants was studied. Differential conditioning experiments were carried out, in which moths had to distinguish between a rewarded (CS+) odorant and an explicitly unrewarded odorant (CS-), choosing odour concentrations giving the same learning rate in previous experiments. The best discrimination was found with beta-myrcene as the rewarded odorant and racemic linalool as the unrewarded. The opposite combination gave lower discrimination, indicating a higher salience for beta-myrcene than for racemic linalool. The moths could also discriminate between beta-ocimene and beta-myrcene, which was surprising, since they activate the same receptor neurone type. No difference in salience was found between these two odorants.
Subject(s)
Association Learning/physiology , Moths/physiology , Odorants , Olfactory Receptor Neurons/metabolism , Smell/physiology , Acyclic Monoterpenes , Alkenes , Animals , Conditioning, Classical/physiology , Electrophysiology , Female , Male , Monoterpenes , Olfactory Receptor Neurons/physiology , Plants/chemistry , Sex FactorsABSTRACT
Honeybees can be trained to associate odorants to sucrose reward by conditioning the proboscis extension response. Using this paradigm, we have recently shown that bees can solve a side-specific task: they learn simultaneously to discriminate a reinforced odor A from a non-reinforced odor B at one antenna (A+B-) and the reversed problem at the other antenna (A-B+). Side-specific (A+B-/B+A-) conditioning is an interesting tool to measure neurophysiological changes due to olfactory learning because the same odorant is excitatory (CS+) on one brain side and inhibitory (CS-) on the opposite side. In the bee brain, the antennal lobe (AL) is the first olfactory relay where the olfactory memory is established. Using calcium imaging, we compared odor-evoked activity in the functional units, the glomeruli, of the two ALs, both in naive and conditioned individuals. Each odor evoked a different pattern of glomerular activity, which was symmetrical between sides and highly conserved among naive animals. In conditioned bees, response patterns were overall symmetrical but showed more active glomeruli and topical differences between sides. By representing odor vectors in a virtual olfactory space whose dimensions are the responses of 23 identified glomeruli, we found that distances between odor representations on each brain side were significantly higher in conditioned than in naive bees, but only for CS+ and CS-. However, the distance between CS+ and CS- representations was equal to that of naive individuals. Our work suggests that side-specific conditioning decorrelates odor representations between AL sides but not between CS+ and CS- within one AL.
Subject(s)
Bees/physiology , Conditioning, Operant/physiology , Discrimination Learning/physiology , Functional Laterality/physiology , Odorants , Olfactory Bulb/physiology , Sense Organs/physiology , Animals , Association Learning , Behavior, Animal , Brain Mapping , Calcium/metabolism , Fluorescent Dyes/metabolism , Organic ChemicalsABSTRACT
The capacity to generalise between similar but not identical olfactory stimuli is crucial for honey bees, allowing them to find rewarding food sources with varying volatile emissions. We studied bees' generalisation behaviour with odours having different biological values: typical floral odours or alarm compounds. Bees' behavioural and peripheral electrophysiological responses were investigated using a combined proboscis extension response conditioning-electroantennogram assay. Bees were conditioned to pure linalool (floral) or to pure isoamyl acetate (alarm) and were tested with different concentrations of both compounds. Electrophysiological responses were not influenced by conditioning, suggesting that the learning of individual compounds does not rely on modulations of peripheral sensitivity. Behaviourally, generalisation responses of bees conditioned to the alarm compound were much higher than those of bees conditioned to the floral odour. We further demonstrated such asymmetrical generalisation between alarm and floral odours by using differential conditioning procedures. Conditioning to alarm compounds (isoamyl acetate or 2-heptanone) consistently induced more generalisation than conditioning to floral compounds (linalool or phenylacetaldehyde). Interestingly, generalisation between the two alarm compounds, which are otherwise chemically different, was extremely high. These results are discussed in relation to the neural representation of compounds with different biological significance for bees.
Subject(s)
Bees/physiology , Conditioning, Classical , Discrimination Learning , Pheromones , Smell , Animals , Behavior, Animal , Electrophysiology , Male , Odorants , Plant Structures , PlantsABSTRACT
Honeybees (Apis mellifera) can be trained to associate an odor stimulus with a sucrose reward. The neural structures involved in the detection and integration of olfactory stimuli are represented bilaterally in the brain. Little is known about the respective roles of the two sides of the brain in olfactory learning. Does each side learn independently of the other, or do they communicate, and if so, to what extent and at what level of neural integration? We addressed these questions using the proboscis extension response (PER) conditioning paradigm applied in a preparation that allows the separation of the two input sides during olfactory stimulations. Bees conditioned to two odorants A and B, one being learned on each side (A+/B+ training), showed in extinction tests rather unspecific responses: They responded to both odorants on both sides. This could be attributable to either a transfer of the learned information between sides, or to a generalization between odorants on each side. By subjecting bees to conditioning on one side only (A+/0 training), we found that the learned information is indeed transferred between sides. However, when bees were trained explicitly to give opposite values to the two odorants on the two sides (A+B-/B+A- training), they showed clear side-specific response patterns to these odorants. These results are used in the elaboration of a functional model of laterality of olfactory learning and memory processing in the honeybee brain.
Subject(s)
Bees/physiology , Functional Laterality/physiology , Generalization, Psychological/physiology , Learning/physiology , Odorants , Smell/physiology , Animals , Conditioning, Operant/physiology , Memory/physiologyABSTRACT
Duchenne Muscular Dystrophy (DMD) originates from deleterious mutations in the dystrophin gene, with a complete loss of the protein product. Subsequently, the disease is manifested in severe striated muscle wasting and death in early adulthood. Dystrophin provides a structural base for the assembly of an integral membrane protein complex. As such, dystrophin deficiency leads to an altered mechanical integrity of the myofiber and a predisposition to contraction-induced damage. However, the development of myofiber degeneration prior to an observed mechanical defect has been documented in various dystrophic models. Although activation of a detrimental signal transduction pathway has been suggested as a probable cause, a specific cellular cascade has yet to be defined. Here, it is shown that murine models of DMD displayed a muscle-specific activation of JNK1. Independent activation of JNK1 resulted in defects in myotube viability and integrity in vitro, similar to a dystrophic phenotype. In addition, direct muscle injection of an adenoviral construct containing the JNK1 inhibitory protein, JIP1, dramatically attenuated the progression of dystrophic myofiber destruction. Taken together, these results suggest that a JNK1-mediated signal cascade is a conserved feature of dystrophic muscle and contributes to the progression of the disease pathogenesis.
Subject(s)
Mitogen-Activated Protein Kinases/metabolism , Muscle, Skeletal/pathology , Muscular Dystrophy, Duchenne/enzymology , Muscular Dystrophy, Duchenne/pathology , Adenoviridae/genetics , Animals , Cells, Cultured , Enzyme Activation , Green Fluorescent Proteins , Humans , Indicators and Reagents/metabolism , Luminescent Proteins/metabolism , MAP Kinase Signaling System , Mice , Mice, Inbred mdx , Mice, Transgenic , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3 , Mitogen-Activated Protein Kinase 8 , Mitogen-Activated Protein Kinases/genetics , Muscle, Skeletal/enzymology , Muscle, Skeletal/metabolism , Muscular Dystrophy, Animal/enzymology , Muscular Dystrophy, Animal/genetics , Muscular Dystrophy, Animal/pathology , Muscular Dystrophy, Duchenne/genetics , Myocardium/enzymology , Myocardium/metabolism , Myocardium/pathology , Phosphorylation , TransfectionABSTRACT
Tuberculosis of the pancreas is a rare gastrointestinal tract entity. This unusual manifestation of tuberculosis should be included in the differential diagnosis of high-risk patients presenting with a pancreatic mass.
Subject(s)
Pancreatic Diseases/diagnosis , Tuberculosis/diagnosis , Adult , Diagnosis, Differential , Humans , Male , Tomography, X-Ray ComputedSubject(s)
Bone Neoplasms/diagnosis , Fibula , Osteoblastoma/diagnosis , Tibia , Aged , Female , HumansABSTRACT
The coupled gas chromatography-proboscis extension assay technique was used on restrained worker bees to study responses to components of an extract of oilseed rape floral volatiles. Bees were stimulated with the effluent from the gas chromatograph after either paired or unpaired conditioning to the extract, or after a control treatment. Proboscis extension activity was elicited in six areas of the chromatogram. However, the number of bees responding in two of these areas were too low to be considered in the present study. One significant area of activity was associated with the major component, (E,E)-alpha-farnesene, whilst the others were associated with several minor components. Although all three groups of bees, irrespective of the treatments applied, showed some responses to the components eluting from the GC column, only bees subjected to paired conditioning consistently responded when re-tested to the mixture. In addition, paired conditioning increased the responsiveness of individuals in terms of the number of bees responding at least once to the effluent from the gas chromatograph. This work confirmed the occurrence of key compounds in floral volatile mixtures. Possible synergistic/inhibitory effects between components, relating to olfactory experience, are discussed.
Subject(s)
Bees/physiology , Conditioning, Classical/physiology , Discrimination, Psychological/drug effects , Discrimination, Psychological/physiology , Oils, Volatile/pharmacology , Plant Oils/chemistry , Animals , Chromatography, Gas/methods , Conditioning, Classical/classification , Conditioning, Classical/drug effects , Pheromones/pharmacology , Sesquiterpenes/pharmacology , Stimulation, Chemical , Taste/drug effects , Taste/physiologyABSTRACT
Olfactory learning in the honeybee was investigated using the conditioned proboscis extension reflex on restrained individuals. We compared, under the same experimental conditions, the most commonly used conditioning procedures, i.e. 1 trial, 3 massed trials (1 min inter-trial intervals), and 3 spaced trials (10 min inter-trial intervals) procedures, using linalool as the conditioned stimulus. Two experiments were performed in which worker bees were subjected to: (1) a single test at different times (30 s to 14 days) after the conditioning procedure; (2) a first test within 3 h after the conditioning procedure, and were then retested daily (up to 5 tests). The memory trace of a learnt odorant stimulus could last for the lifetime of the bee, even after a single association with sugar. Repeated tests with 1 day inter-test duration induced a strong decrease of the response level, this effect being more pronounced after a 1-trial conditioning.
Subject(s)
Bees , Learning , Memory , Smell , Animals , Conditioning, Classical , Time FactorsSubject(s)
Hypolipoproteinemias/genetics , Lecithin Cholesterol Acyltransferase Deficiency/genetics , Adult , Anemia, Hemolytic/complications , Corneal Opacity/complications , Female , Humans , Kidney/pathology , Lecithin Cholesterol Acyltransferase Deficiency/blood , Lecithin Cholesterol Acyltransferase Deficiency/complications , Lipids/blood , Proteinuria/complicationsABSTRACT
Over 100 patients have received cyclic treatment with polyclonal 131I labeled anti-ferritin and anti-carcinoembryonic antigen (CEA) antibodies from different animal species (rabbit, pig, cynomolgous monkey, bovine, and baboon). Because survival was prolonged from original cyclic treatment, retreatment with original antibodies (recycling) became a necessary consideration. An assay using autoradiography of Ouchterlony gels, with diffusion of patients' sera against the varied radiolabeled antibodies, was developed to detect anti-antibody precipitin bands. Anti-antibody could be detected with a sensitivity to the 60 ng level. Sera from 35 patients given from 1 to 7 separate cycles (2 injections/week, total antibody 6 mg/cycle) of radiolabeled foreign antibody were studied for the production of anti-antibodies. Anti-antibodies were detected in 11 of 22 primary hepatoma patients studied, 3 of 4 intrahepatic biliary cancer patients, and 0 of 9 Hodgkin's disease patients. In all but two of the patients, the anti-antibodies produced were specific for the species used in the treatment of the patient. Eight patients were reinjected (recycled) with previously used antibodies and the presence or absence of precipitin bands correlated with the ability of these antibodies to deposit in the tumor or to be rapidly degraded. The importance of this assay is its simplicity, sensitivity, and the rapid detection of anti-antibody activity for patients requiring treatment with radiolabeled antibodies.
Subject(s)
Antibodies, Anti-Idiotypic/analysis , Carcinoma, Hepatocellular/radiotherapy , Gallbladder Neoplasms/radiotherapy , Hodgkin Disease/radiotherapy , Liver Neoplasms/radiotherapy , Carcinoembryonic Antigen/immunology , Carcinoma, Hepatocellular/immunology , Ferritins/immunology , Gallbladder Neoplasms/immunology , Hodgkin Disease/immunology , Humans , Immunodiffusion/methods , Iodine Radioisotopes/therapeutic use , Liver Neoplasms/immunologyABSTRACT
Undifferentiated murine 402AX teratocarcinoma cells do not express MHC antigens when passaged in vitro or in vivo in genetically susceptible host mice. When passaged in vivo in genetically resistant mice, however, the tumor cells become H-2b antigen positive regardless of the H-2 haplotype of the resistant host mouse. The present studies use monoclonal anti-H-2b antibodies to corroborate these earlier findings, which were performed with conventional antisera. Previous studies have established that host bone marrow plus lymphoid cells from resistant primed donors regulate tumor cell H-2b antigen expression. Using bone marrow and mature lymphoid cell reconstitution techniques, the present studies indicate that splenic Ig- cells from genetically resistant host mice are the most efficient lymphoid cell subpopulation in tumor cell H-2b antigen induction. Ig+ spleen cells also reconstitute the capacity to induce teratocarcinoma cell H-2 antigens but are less effective than Ig- spleen cells. Tumor cell H-2 antigen induction in C57BL/6 beige mice is impaired compared to C57BL/6 hosts, which suggests that host NK cells may also be involved in tumor cell H-2 antigen induction. Reconstitution of lethally irradiated resistant hosts for teratocarcinoma cell H-2 antigen expression requires bone marrow plus resistant primed lymphoid cell subpopulations; bone marrow alone is insufficient. These results indicate that multiple splenic lymphoid cell subpopulations requiring a radiosensitive host environment and/or factor for differentiation regulate teratocarcinoma 402AX H-2b antigen expression in vivo in genetically resistant mice.