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Glucocortidoid sensitivity assessed in peripheral blood cells do not correlate with the feedback sensitivity of the hypothalamo-pituitary adrenal AXIS.

Glucocorticoids (GC) affect virtually all organ systems, acting mainly via the glucocorticoid receptor (GR). The immune system is the best characterized tissue for assessing GC sensitivity. It is well established that the immune system GC sensitivity varies widely between normal subjects. However, it remains unclear whether measurements of the immune system GC-sensitivity reflect the GC-sensitivity in other GC target tissues of the same individual. Thus, in the present study we compared the GC sensitivity of the immune system, assessed by determining the dexamethasone inhibition of LPS-induced TNF-alpha production in peripheral leukocytes, with the feedback sensitivity of the HPA axis, assessed by a very low dose dexamethasone (0.25 mg) suppression test, in sixteen healthy volunteers. We observed a wide variation in the magnitude of the responses in the two GC targets. However, and in agreement with a number of previous reports, in a given subject the GC sensitivity of the immune system did not correlate with that of HPA axis inhibition, indicating a tissue specificity of GC sensitivity in the same individual. In summary, the bulk of current evidence suggests that GC sensitivity is tissue specific for a given individual. Additional studies are warranted to elucidate the exact mechanism(s) involved in the differential GC tissue responsiveness.

Journal Article↗

The migratory behavior of T blasts to contact sensitivity reactions in activelyand passively sensitized mice.

The arrival of cells from lymph nodes immunized with the contact sensitizing agents oxazolone and picryl chloride at ears challenged with these antigens was studied inmice using the technique of labelling with -51Cr. An apparent specificity of arrival was seen because the immune cells transfered contact sensitivity passively, giving rise to an inflammatory response in the ear, to which a subpopulation of cells (T blasts) was non-specifically attracted. It was also shown that there are at least two distinct populations of cells with the ability to move to inflammatory sites: the first, found in immunized lymph nodes, moves to contact sensitivity reactions in both actively and passively sensitized mice; the second, found in bone marrow and oil-induced peritoneal exudates, moves to contact sensitivity reactions in actively sensitized mice, whereas in passively sensitized mice, the arrival of these cells at contact sensitivity reaction is poor. It is suggested that the ability of T blasts to move to sites of inflammation my be useful as an assay technique for contact sensitivity reactions.

Animals↗

[Comparative studies on the sensitivity of smooth bronchial muscles to catecholamines during sensitization with various allergens].

An attempt has been made to compare the effects produced by adrenergic agents on smooth bronchial muscles of normal and BCG- as well as ovalbumin-sensitized guinea pigs. The method of determining the state of relaxation of the isolated bronchial tree was used to ascertain the degree of sensitivity to adrenergic agents of smooth bronchial muscles. Experiments conducted on a total of 34 guinea pigs showed a considerable decrease in the response of smooth bronchial muscles to novodrine, adrenaline, and noradrenaline subsequent to BCG and ovalbumin sensitization of experimental animals. In normal guinea pigs, minimal relaxation of smooth tracheal muscles was brought about by 7.10(-8) - 1.10(-7) G/ml novodrine, 1.10(-7) - 9.10(-7) g/ml adrenaline, and 1.10(-6) - 8.10(-6) g/ml noradrenaline. For BCG-sensitized animals, the data obtained were 3.10(-7) - these agents of smooth bronchial muscles of guinea pigs was more clearly evident in BCG-sensitized 2.10(-6) g/ml, 1.10(-6) - 2.10(-6) g/ml, and 3.10(-6) - 6.10(-6) g/ml, respectively. The decrease in sensitivity to bronchi during the process of sensitization is believed to be responsible for the decrease in response to animals than in ovalbumin-sensitized guinea pigs. A partial blockade of beta-adrenergic receptors of catecholamines. The degree of partial blockade is dependent upon the kind of sensitization.

Allergens↗

Characteristics of the histamine-sensitive calcium store in vascular smooth muscle. Comparison with norepinephrine- or caffeine-sensitive stores.

Using the microfluorometry of an intracellularly trapped calcium indicator dye, quin2, characteristics of intracellular Ca2+ store sites sensitive to histamine, norepinephrine, or caffeine were investigated using rat vascular smooth muscle cells in primary culture at 25 degrees C. With similar time courses, both histamine- and the norepinephrine-sensitive Ca2+ store sites were readily depleted in Ca2(+)-free medium and almost completely replenished by loading the cells with 1.0 mM Ca2+ solution for 3 min, while the caffeine-sensitive Ca2+ store site was little affected. In the absence of extracellular Ca2+, transient elevations of cytosolic Ca2+ repeatedly appeared in response to repetitive applications of histamine, norepinephrine, or caffeine, with progressive reductions in peak levels. Histamine released Ca2+ from the norepinephrine-sensitive store site and norepinephrine released Ca2+ from the histamine-sensitive one. On the other hand, caffeine had little effect on the histamine- and/or the norepinephrine-sensitive Ca2+ store site in Ca2(+)-free medium, and vice versa. We propose that the location and mechanisms of release of Ca2+ of the histamine-sensitive Ca2+ store site are identical with events at the norepinephrine-sensitive site, and differ from the caffeine-sensitive one, in vascular smooth muscle cells in primary culture.

Aminoquinolines↗

Induction of sensitization and tolerance in contact sensitivity with haptenated epidermal cells in the guinea-pig.

Haptenated murine Langerhans' cells (LCs) have been reported to induce contact sensitivity when injected via the subcutaneous, intraperitoneal and, in some instances, the intravenous route. Similar studies were undertaken to elucidate the role of the LC in the induction of contact sensitivity in the guinea-pig. The subcutaneous injection of dinitrophenylated epidermal cells induced hapten-specific contact sensitivity in a dose-dependent fashion. This contrasts with the tolerance that was induced by the intravenous or intraperitoneal injection of similarly haptenated cells. Contact sensitivity by haptenated epidermal cells could be induced in syngeneic and allogeneic recipients and did not require the transfer of viable cells. Using the monoclonal antibody MSgp2, which detects LCs, LC-enriched and LC-depleted populations were prepared by an 'indirect antibody' panning technique. It was found that a haptenated LC-depleted epidermal cell population (0.1% LC) induced the same degree of contact sensitivity or tolerance, depending on the route of immunization, as a haptenated 'freshly isolated' epidermal cell population (1% LC). Whereas, a purified population of haptenated LC (85-90%) induced no significant degree of contact sensitivity or tolerance. These results confirm our previous conclusions based the in vivo depletions of Langerhans' cells, and suggest that the epidermal Langerhans' cell is not essential for the induction of contact sensitivity in the guinea-pig. However, this does not exclude the possibility that the LC is involved in the elicitation of contact sensitivity in a sensitized animal.

Animals↗

The cellular analog of sensitization in Aplysia emerges at the same time in development as behavioral sensitization.

Recent studies examining the development of learning and memory in the gill and siphon withdrawal reflex of Aplysia have shown that different forms of learning emerge according to very different developmental timetables. For example, in the previous paper, Rankin and Carew (1988) showed that, whereas habituation and dishabituation emerge early in juvenile development (in stages 9 and 10, respectively), sensitization emerges at least 60 d later (in late stage 12). This developmental separation of different learning processes provides the opportunity to examine the unique contribution of specific cellular mechanisms to each form of learning. As a first step in this cellular analysis, in the present paper we have examined the development of the cellular analog of sensitization (facilitation of nondecremented EPSPs) in the identified giant neuron R2, which can serve as a monitor of the afferent input in the gill and siphon withdrawal reflex (Rayport and Camardo, 1984). We have found 2 striking parallels between the development of behavioral sensitization and the development of its cellular analog: (1) Behavioral sensitization, produced by tail shock, emerges very late in juvenile development (stage 12), and the cellular analog of sensitization (produced by activation of the tail pathway) emerges by exactly the same late juvenile stage; (2) prior to the emergence of behavioral sensitization, tail shock unexpectedly was found to produce significant reflex depression (Rankin and Carew, 1988), and prior to the emergence of the cellular analog of sensitization, activation of the tail pathway was found to produce significant depression of the synaptic input in the reflex pathway. Thus, the cellular analog of sensitization in the CNS develops and matures in close temporal register with the development of behavioral sensitization in juvenile Aplysia.

Animals↗

Stress-induced sensitization and glucocorticoids. I. Sensitization of dopamine-dependent locomotor effects of amphetamine and morphine depends on stress-induced corticosterone secretion.

Repeated exposures to stress sensitize motor and addictive effects of drugs of abuse. Recently, it has been shown that stress-induced behavioral sensitization depends on the secretion of glucocorticoids. We investigated if sensitization of dopamine-dependent effects of psychostimulants and opioids was influenced by glucocorticoid. Sensitization of the dopaminergic response to drugs is considered the neural substrate of behavioral sensitization and has been implicated in vulnerability to drug abuse. Dopamine-dependent effects of psychostimulants and opioids were evaluated by injecting either amphetamine into the nucleus accumbens (10 micrograms/side) or morphine into the ventral tegmental area (VTA) (1 microgram/side). The locomotor response to psychostimulants and opioids injected in these brain areas depends on the mesencephalic dopaminergic transmission. Drug-induced locomotion was compared in male rats in which corticosterone secretion was either in +tct or experimentally suppressed by an adrenalectomy associated with a substitutive treatment reproducing basal levels of the hormone. Eight days of food restriction (80% of the initial body weight) were used as a stressor. Suppression of stress-induced corticosterone secretion abolished food restriction-induced sensitization of the locomotor effects of intra-accumbens amphetamine and intra-VTA morphine. This effect was corticosterone dependent since the restoration of corticosterone levels in the range of those induced by stress totally reinstates sensitization. Our results suggest that glucocorticoids control stress-induced sensitization by changing the sensitivity of the mesencephalic dopaminergic transmission to drugs of abuse. Since dopaminergic effects of drugs are related to their addictive properties, secretion of glucocorticoids may be one of the factors determining the enhanced vulnerability to drugs observed in stressed subjects.

Amphetamine↗

Sensitization induced by kindling and kindling-related phenomena as a model for multiple chemical sensitivity.

It has been suggested that the neurobehavioral dysfunction observed in persons presenting with symptoms of Multiple Chemical Sensitivity (MCS) syndrome involves sensitization of neural circuits. Two hypotheses for the route of exposure in induction of neural sensitization in MCS are: (a) direct chemical stimulation of olfactory processes, or (b) general systemic response to inhaled chemicals. In either case, the mechanism of action may involve chemical kindling or kindling-related phenomena. A neural sensitization mechanism based on kindling or kindling-related phenomena is attractive and has been previously demonstrated in both in vitro and in vivo animal models. Without a testable animal model for chemically mediated induction of MCS, however, any argument that MCS is mediated by kindling or kindling-related phenomena is reduced to the circular argument "the mechanism of sensitization is sensitization." The present survey provides an overview of the experimental paradigms that result in sensitization, differentiated on the basis of probable neurophysiological and neurochemical mechanisms. Neurophysiological potentiation, electrical kindling, chemical kindling and behavioral sensitization are evaluated and discussed in relationship to MCS.

Animals↗

RBL cells expressing human Fc epsilon RI are a sensitive tool for exploring functional IgE-allergen interactions: studies with sera from peanut-sensitive patients.

Rat basophilic leukemia cells (RBL SX-38) express the alpha, beta, and gamma chains of human Fc epsilon RI. Following sensitization with IgE from a subset of allergic human donors, these cells can be triggered by exposure to anti-IgE or to very low concentrations of specific allergens. We examined 18 sera from patients who were highly sensitive to peanuts by history and had anti-peanut IgE by in vitro testing. The ability of these sera to sensitize the RBL SX-38 cells for degranulation with peanut allergens correlates very well with the absolute amount of anti-peanut IgE (r=0.95; p<0.001). The most effective sera contained at least 50 kU/l of total IgE and at least 15 kU/l of peanut-specific IgE. RBL SX-38 cells sensitized with these sera degranulated optimally upon exposure to anti-IgE (net degranulation of 40+/-8%, means+/-S.D.; n=8) and to a 10(5)-10(6) dilution of crude peanut extract (CPE) (37+/-7% net degranulation; 93+/-13% of that seen with anti-IgE). This assay is quite sensitive. Cells sensitized with selected sera are activated by exposure to a 1:10(7) dilution of the CPE containing picogram amounts of peanut allergens. This assay is also quite specific. Cells sensitized with sera from patients with anti-peanut IgE and no detectable IgE against soybean, walnut or grass pollen did not degranulate following exposure to these latter antigens. The converse was also true; cells sensitized with sera from patients without anti-peanut IgE did not react to peanut. These data demonstrate that RBL cells expressing human Fc epsilon RI form the basis of a useful model system for the detection of allergens and for the study of IgE-allergen interactions.

Adult↗

Differential sensitivity of thoracic malignant tumors to adenovirus-mediated drug sensitization gene therapy.

Malignant mesothelioma may prove to be an attractive candidate for somatic gene therapy with replication-deficient recombinant adenovirus transfer of a toxic, or drug sensitization gene. Transfer of the herpes simplex thymidine kinase type I gene (HSVtk), followed by exposure to the acyclic nucleoside drug ganciclovir, has been shown to be an effective tumor cell killing system. To study generalized applicability, we tested a number of thoracic malignant cell lines for their sensitivity to gancyclovir after infection with an adenoviral vector containing the HSVtk gene (Ad.RSVtk). Using the concentration of gancyclovir required to kill 50% of the cells (IC50) as a measure of sensitivity, we detected variable sensitivity among cell lines, with mesothelioma most sensitive (IC50 = 0.075 to 2.8 mumol/L gancyclovir), and non-small-cell carcinoma lines having an intermediate sensitivity (IC50 = 1.5 to 100 mumol/L). In contrast, an ovarian carcinoma line was extremely resistant (IC50 > 2000 mumol/L). To study the possible mechanisms for these differences, we studied cell lines with regard to their ability to be infected with an adenoviral vector containing a marker gene (Ad.CMVlacZ) and expression of the vitronectin receptor alpha v (an integrin cell adhesion molecule shown to be required for adenovirus internalization after initial binding). We found that the degree of lacZ transduction correlated with HSVtk sensitivity, whereas vitronectin receptor expression did not, suggesting that differences in initial viral binding ability, rather than internalization, may explain the sensitivity differences seen in vitro.

Adenoviridae↗

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

A theoretical framework for evaluating the sensitivity of surveillance for detecting wild poliovirus: I. Factors affecting detection sensitivity in a person with acute flaccid paralysis.

Surveillance for cases of acute flaccid paralysis provides a means for detecting circulating wild poliovirus in a population and therefore is crucial to the global polio eradication effort. An initial step toward developing a more general framework for understanding the sensitivity of the acute flaccid paralysis surveillance system is presented by first specifying four categories of sensitivity involved: laboratory sensitivity, specimen sensitivity, person sensitivity, and population sensitivity. Using this framework, estimates for specimen sensitivity (the probability that virus will be detected in a specimen collected from an infected person) and the prevalence of infection are derived and applied to surveillance data from three regions. On the basis of the framework, our analysis indicates that a second specimen may significantly increase person sensitivity under some circumstances but provides little improvement under others.

False Negative Reactions↗

Introduction to special section on sensitivity analysis and summary of NCSU/USDA workshop on sensitivity analysis.

This guest editorial is a summary of the NCSU/USDA Workshop on Sensitivity Analysis held June 11-12, 2001 at North Carolina State University and sponsored by the U.S. Department of Agriculture's Office of Risk Assessment and Cost Benefit Analysis. The objective of the workshop was to learn across disciplines in identifying, evaluating, and recommending sensitivity analysis methods and practices for application to food-safety process risk models. The workshop included presentations regarding the Hazard Assessment and Critical Control Points (HACCP) framework used in food-safety risk assessment, a survey of sensitivity analysis methods, invited white papers on sensitivity analysis, and invited case studies regarding risk assessment of microbial pathogens in food. Based on the sharing of interdisciplinary information represented by the presentations, the workshop participants, divided into breakout sessions, responded to three trigger questions: What are the key criteria for sensitivity analysis methods applied to food-safety risk assessment? What sensitivity analysis methods are most promising for application to food safety and risk assessment? and What are the key needs for implementation and demonstration of such methods? The workshop produced agreement regarding key criteria for sensitivity analysis methods and the need to use two or more methods to try to obtain robust insights. Recommendations were made regarding a guideline document to assist practitioners in selecting, applying, interpreting, and reporting the results of sensitivity analysis.

Food Contamination↗

A realistic approach to the sensitivity of PCR-DGGE and its application as a sensitive tool for the detection of clonality in cutaneous T-cell proliferations.

The practical value of the detection of clonality within the T-cell receptor gamma locus by polymerase chain reaction for the diagnosis of cutaneous T-cell lymphomas is well known. However, studies dealing with this subject so far, with special emphasis on the sensitivity of the technique in comparison to, for example, Southern blotting have used mixtures of DNA in various concentrations instead of using mixtures of the cells involved, which would reflect the in vivo situation in a more realistic scope. The purpose of this study was therefore to determine the sensitivity and the limitations of the PCR assay by dilution experiments, using mixtures of cells. Furthermore we studied its applicability to cutaneous T-cell proliferative disorders. Two clonal T-cell lines (MyLa and Jurkat) served as positive control. Dilutions of MyLa cells, cultured normal human keratinocytes and peripheral blood mononuclear cells from lymphoma negative volunteers were used to assess the sensitivity of the PCR-DGGE assay. Skin samples from 4 patients with cutaneous T-cell lymphoma, 1 lesional lymph node, 2 blood samples from a patient with Sézary syndrome and 4 lymphoma-negative tissue samples were analysed. Two samples were uncertain for diagnosis of lymphoma. The PCR-DGGE assay consisted of a 2-round nested PCR with consensus primers within the TCR-gamma locus followed by electrophoretic separation of the product along a denaturing urea/formamide gradient gel. PCR-DGGE sensitivity was, to our knowledge, for the first time investigated for mixtures of lymphocytes (clonal and polyclonal) and keratinocytes. Clonal T-cells were detected in a concentration between 1-0.1% in keratinocytes, whereas the sensitivity was generally lower upon dilution in peripheral blood mononuclear cells or in a mixture of keratinocytes and peripheral blood mononuclear cells. Nevertheless, T-cell clonality was detected in 2 blood samples of a patient with Sézary syndrome, which were negative by Southern blot analysis. The crucial point of this work was the new approach to establish the sensitivity of the PCR-DGGE, in a way which more closely mimics the condition of clinical specimens. Instead of mixing and amplifying DNA extracted from clonal T-cell lines and polyclonal bone marrow cells, we amplified DNA from clonal and polyclonal cells which had been mixed in various ratios before DNA extraction. Polymerase chain reaction in conjunction with denaturing gradient gel electrophoresis is a sensitive and versatile molecular tool for the assessment of clonality of suspect cutaneous lesions. The determination of sensitivity using DNA extracted from premixed cells more closely corresponds to the actual test situation when testing skin samples.

Blotting, Southern↗

White paper: Neuropsychiatric aspects of sensitivity to low-level chemicals: a neural sensitization model.

The present paper summarizes the proposed time-dependent sensitization (TDS) and partial limbic kindling model for illness from low-level chemicals; reviews and critiques prior studies on CNS aspects of multiple chemical sensitivity (MCS); and outlines possible experimental approaches to future studies. TDS is the progressive and persistent amplification of behavioral, neurochemical, endocrine, and/or immunological responses to repeated intermittent stimuli over time. Partial limbic kindling is a progressive and persistent lowering of the threshold for eliciting electrical afterdischarges, but not motor seizures, in certain brain structures such as amygdala and hippocampus; behavioral consequences include increased avoidant behaviors. The focus of the paper is the controversial claim of altered sense of smell and illness from low levels of environmental chemicals (i.e., "cacosmia"), levels that should not have any biologically harmful effects by the rules of classical neurotoxicology. A major perspective of this paper is that the phenomenology of MCS is similar to that of time-dependent sensitization (reverse tolerance) and tolerance as studied in the substance abuse literature. The TDS model for MCS proposes that neurobiological amplification underlies the symptoms and phenomenology of these patients, including their behavioral features of heightened affective and somatic distress. It is hypothesized that MCS patients, who are mostly women, may be individuals who sensitize to substances rapidly and to the extreme, to the point of aversive symptomatology with less complete capacity for development of tolerance. Possible parallels between MCS and TDS include: (a) initiation by single or multiple intermittent stimuli; (b) lasting changes in subsequent reactivity to low levels of chemically unrelated substances; (c) cross-sensitization between the stressors and pharmacological agents; (d) greater vulnerability of individuals who are female, who have certain genetic characteristics, and/or who may be hyperreactive to novelty (cf. trait shyness); (e) lack of obvious differences between sensitized and unsensitized individuals at baseline without eliciting exposures; (f) bidirectionality (bipolarity) of sensitized responses; (g) both context-dependent (conditioned) and context-independent (unconditioned) amplification of responses. To minimize variability between studies, research in this area needs (a) consensus on a working case definition of MCS or at least of cacosmia as a specific symptom in a subset of well-defined medical and psychiatric disorders; and (b) proper design of chemical challenge studies in MCS, controlling for individual differences in sensitizability and for the properties of sensitization (e.g., repeated intermittent exposure tests) and tolerance (e.g., removal from customary ambient air exposures prior to testing).

Central Nervous System↗

Neurobiological sensitization models of post-traumatic stress disorder: their possible relevance to multiple chemical sensitivity syndrome.

Neurological sensitization has been proposed as a model for post-traumatic stress disorder (PTSD) (Lipper et al., 1986; van der Kolk, 1987; Friedman, 1988; Post et al., 1988, 1994; Charney et al., 1993). Laboratory paradigms in which repeated exposure to a discrete stimulus is associated with progressive intensification of a neurophysiologic, behavioral, or pharmacologic response has many parallels with the sequence of events that precipitates PTSD. Investigators with other clinical interests have also been attracted to sensitization models. Specifically, Bell and associates (1992) have proposed that olfactory-limbic kindling is a very good model for understanding the etiology of multiple chemical sensitivity (MCS) syndrome. A number of articles in this volume have addressed the goodness-of-fit between this model and MCS. My major assignment is to review laboratory data and clinical observations pertinent to sensitization models of PTSD. I will show that although there are intriguing parallels between the two phenomena, one must have great respect for the complexity and polymorphism of both sensitization and PTSD before grasping for simplistic theoretical conclusions. Secondly, I will address the following question; if both PTSD and MCS can be understood as sensitization phenomena, are PTSD patients at greater risk to develop MCS and vice versa? This article is divided into four sections: a) a description of three distinct sensitization phenomena; b) a description of the symptoms of PTSD; c) a review of the applicability of sensitization models to the clinical phenomenology of PTSD; and d) a review of the hypothesis that PTSD patients might be more vulnerable to MCS.

Animals↗

A comparison of hyperthermia cisplatin sensitization in human ovarian carcinoma and glioma cell lines sensitive and resistant to cisplatin treatment.

Two pairs of human tumor cell lines (glioma and ovarian carcinoma (OvCa) each having a parental cell line and cisplatin-resistant variant, were evaluated for (a) cisplatin response, (b) hyperthermia response, and (c) combined hyperthermia and cisplatin response. The two resistant lines had comparable resistant responses while for the parental lines, the OvCa was more sensitive than the glioma to cisplatin doses up to 14 microgram/ml. For the hyperthermia response, the OvCa parental line was more resistant than the variant line at low-temperature hyperthermia (41 degrees C or 42 degrees C) but became more sensitive at high temperature (45 degree C). For the glioma, the parental line was more sensitive to hyperthermia at all temperatures tested. Hyperthermia caused sensitization to cisplatin in all cell lines but was generally greater in the glioma cell lines. In the OvCa system, hyperthermia had a slightly greater sensitizing effect on the resistant cell lines, while in the glioma the opposite was true. The degree of sensitization increased with hyperthermia temperature. In summary, the results showed that there is no cross- resistance for hyperthermia and cisplatin, that the degree of thermal sensitization is not reduced in cisplatin- resistant cell lines, and that cisplatin thermal sensitization is cell-line and temperature dependent. Thus, hyperthermia can effectively improve tumor cell response to cisplatin and may be useful in overcoming resistance to cisplatin.

Carcinoma↗

Cutaneous sensitivity induced by immunization with irradiated Schistosoma mansoni cercariae. I. Induction, elicitation, and adoptive transfer analysis of cell-mediated cutaneous sensitivity.

Exposure of C57BL/6 mice to highly irradiated (50 kR) cercariae of Schistosoma mansoni leads to the development of partial resistance against subsequent challenge with unattenuated cercariae. We have analyzed the cellular immune responses that occur during the afferent and efferent phases of this protective sensitization. Mice were immunized by exposure to irradiated S. mansoni cercariae. After challenge with irradiated cercariae, delayed-type (18-72 hr) cutaneous sensitivity reaction sites were rich in mononuclear cells and eosinophils. This reactivity was established by 4 days after sensitization, reached its maximum between 7 and 14 days after sensitization, and was maintained for over 20 weeks. These challenge reactions could be abrogated by treatment with either 200 mg/kg cyclophosphamide or 5 mg of hydrocortisone. Syngeneic adoptive transfer of cutaneous sensitivity was accomplished with lymphoid cells from the draining lymph nodes or spleens of mice sensitized 7-14 days previously. Negative selection studies of nylon-wool non-adherent cells from sensitized donors demonstrated that the cells responsible for transferring this eosinophil-rich, delayed-type cutaneous sensitivity to S. mansoni irradiated cercariae were Thy-1+, Lyt1+, Lyt2-, surface Ig- lymphocytes.

Animals↗