Sensitization Procedure Research Articles

Behavioral treatment of zoophilic exhibitionism

We describe here a case of zoophilic exhibitionism involving a mildly mentally retarded man who masturbated in front of large dogs of either sex. Unlike most exhibitionists, he did not expose himself to women, and unlike most zoophiles, he never desired direct sexual contact with animals. His paraphilia, however, was responsive to a behavioral program comprising masturbatory satiation, covert sensitization, and stimulus control procedures.

Epithelial modulation of thromboxane A2 and PAF involvement in IgE- and IgG-mediated guinea pig anaphylaxis

The role of prostanoids and platelet-activating factor (PAF) was studied inthe in vitro response of guinea pig trachea to immunochallenge according to the presence or the absence of the epithelial layer and to the sensitization procedure leading to the preferential synthesis of immunoglobulin E (IgE) or immunoglobulin G (IgG) antibodies. Indomethacin, a cyclooxygenase inhibitor, potentiated the antigen-induced contractions both in IgE and IgG models, suggesting the involvement of relaxant prostaglandins (PGs), independently of the presence of the airway epithelium. UK-38485, a thromboxane synthetase inhibitor, did not modify the tracheal response to antigen in the IgE model. However, this compound enhanced the maximum contractile response to antigen of the intact tracheal strips of IgG-sensitized guinea pig, but reduced the contractile response of the epithelium-free tracheal strips. Two potent non-structurally related PAF antagonists, Ro 19-3704 and BN 52021, reduced antigen-induced contraction of the epithelium-free tracheal strips in the IgE model. In contrast, these compounds did not affect the contractile responses of the preparations in the IgG model. These results suggest the selective implication of thromboxane A2 and PAF, in IgG- and IgE-mediated guinea pig anaphylaxis respectively. Finally, these results indicate that thromboxane A2 (TXA2) and PAF are potent inducers of epithelium-derived mediators.

BN rats do not reject F344 brain allografts even after systemic sensitization

Embryonic brain tissue allografts under many circumstances survive transplantation into the brain. It is generally believed that such grafts will not survive if the host animal is systemically sensitized, by skin grafting or other means, to major histocompatibility complex (MHC) antigens of the donor animal. We have found that F344 brain grafts survive in BN hosts even when the host is systemically sensitized to F344 tissue. Embryonic cerebral neocortex from F344 donors was transplanted into BN host rats (n = 95). Subsequently, the host rats were systemically sensitized with donor skin (n = 25), brain tissue (n = 41), or spleen cells (n = 6) and compared with a control group of rats consisting of allografts with no sensitization or sham procedures (n = 23). Rejection of the transplants in BN rat hosts was not provoked by any of the sensitization methods tested. Minor immunological responses that did not result in rejection were, however, present in many host animals. We did not observe infiltration of W3/13+ T cells and OX8+ cytotoxic lymphocytes in any of the groups. Nevertheless, substantial infiltrations of OX6+ antigen-presenting cells and W3/25+ helper T cells were present. There was also an extensive enhancement of MHC class I immunoreactivity in parts of the grafted tissue developing within the third ventricle, but not for the same type of graft in the lateral ventricle. This increase of MHC class I expression was not accompanied by infiltration of cytotoxic T cells. Our findings thus suggest that neural graft rejection depends on general genetic susceptibility to immune reactions, particularly experimental allergic encephalomyelitis and not only on disparity between donor and host antigens encoded by the MHC. Moreover, enhancement of MHC class I and class II expression within transplanted tissue does not predict graft rejection.

DYNAMITE: an efficient automatic test pattern generation system for path delay faults

The authors present DYNAMITE, a versatile and efficient automatic test pattern generation system for path delay fault. Based upon a ten-valued and a three-valued logic, the deterministic test pattern generation algorithm incorporated in DYNAMITE is capable of generating both robust and nonrobust tests for path delay faults. Particular emphasis has been placed on coping with the main disadvantage of the path delay fault model. The distinct features of DYNAMITE consist of the application of a powerful implication procedure and a stepwise path sensitization procedure, which has the capability of proving large numbers of path faults as redundant by a single test generation attempt. The delay test generation process is further optimized by the use of a new path selection procedure which aims at the identification of paths, which can successfully be sensitized, and the elimination of redundant, i.e., unsensitizable, paths.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

Antigen‐dependent activation of alveolar macrophages from ovalbumin‐sensitized guinea‐pigs: relevance of the route of administration and the amount of antigen provided

Alveolar macrophages from guinea-pigs sensitized by different amounts of ovalbumin, administered either by subcutaneous injection or aerosol exposure, liberate increased amounts of arachidonic acid and thromboxane B2 when challenged in vitro with ovalbumin. This antigen-dependent activation of macrophages was immunospecific. The comparison between different sensitization procedures showed that the aerosol exposure was the most efficient with respect to the activation of macrophages, as cells from guinea-pigs sensitized subcutaneously were poorly activated by the antigen unless high doses were used for sensitization. The antigen-dependent activation of macrophages was affected by acid and neutral washings, suggesting the involvement of a loosely bound antibody that could not be identified. These observations suggest that, as mast cells and basophils, alveolar macrophages from actively sensitized guinea-pigs contribute to the allergic reaction by an antibody-mediated mechanism.

Low allergenicity of clonidine impedes studies of sensitization mechanisms in guinea pig models

During clinical trials, a clonidine transdermal device has been found to induce clonidine-specific allergic contact dermatitis in up to 25% of patients during a treatment period of 1 year. Using 3 different guinea pig strains, development was attempted of an experimental guinea pig model that would allow for in-depth studies into the mechanism of sensitization, and a possible role of transdermal device components. Transient low-level clonidine allergy could be obtained only in a minority of animals, with severe sensitization procedures departing from epicutaneous applications, combined with intradermal (adjuvant) FCA injections. Sensitization was not potentiated by additional booster procedures, including cyclophosphamide pretreatment, nor any of the putative cofactors (UV-treatments, C. parvum or acetaldehyde involvement) studied. These results suggest that the persistent skin contacts in man, with transdermal devices for sustained drug delivery, generate unique conditions favouring the development of allergic contact dermatitis, which are difficult to mimic in experimental animal models. Thus, clinical allergy may develop even to extremely weak sensitizing drugs that can be safely used orally, and escape most currently available predictive contact allergy animal models. Clinical studies remain unavoidable for studying factors that may reduce sensitization rates to more acceptable levels.

Improved deterministic test pattern generation with applications to redundancy identification

The authors present several concepts and techniques aiming at a further improvement and acceleration of the deterministic test-pattern-generation and redundancy identification process. In particular, they describe an improved implication procedure and an improved unique sensitization procedure. While the improved implication procedure takes advantage of the dynamic application of a learning procedure, the improved unique sensitization procedure profits from a dynamic and careful consideration of the existing situation of value assignments in the circuit. As a result of the application of the proposed techniques, SOCRATES is capable of both successfully generating a test pattern for all testable faults in a set of combinational benchmark circuits, and of identifying all redundant faults with less than ten backtrackings.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

Covert Sensitization: Alternative Treatment Procedures for Alcoholism

Twenty-nine outpatients (24 men) with a history of problem-drinking and alcohol dependence were assigned at random to one of three covert sensitization procedures varying in the nature of stimulus elements in aversion scenes. Group 1 received standard nausea imagery, whereas Group 2 received similar scenes “assisted” by noxious odors. Imagery used in Group 3 scenes was unrelated to nausea but focused instead on disturbing potential consequences of drinking. The occurrence of conditioned aversion responses (CR) was verified by observational, self-report and physiological measures. The observed pattern and frequency of conditioning corresponded closely to data reported by Elkins (1980). Favourable outcomes at 18 months (abstinent, controlled or improved) were observed in 45, 56 and 67% of clients in each group, respectively. The groups did not differ significantly in effectiveness. Within both of the nausea sensitization groups (1 and 2), successful remission at 18 months occurred only in individuals who had shown CR, whereas in emotive sensitization (Group 3) there was no apparent relationship between conditioning and outcome.

A Human Monoclonal Antibody to Cytokeratin Intermediate Filament Antigens Derived from a Tumor Draining Lymph Node

Human lymphocytes derived from a lymph node draining a primary breast adenocarcinoma were fused with the mouse myeloma P3X63Ag8.653 to generate human-mouse hybridomas secreting human monoclonal antibodies (MAbs) to tumor associated antigens (TAAs). One of the resulting human MAbs, YBB 190 (IgM) is described. Enzyme-linked immunosorbent assays (ELISA) employing membrane and cytosol fractions of human tissues demonstrated YBB 190 reactivity against cytosol but not membrane components of malignant and normal epithelial tissues. When tested by an indirect immunoperoxidase staining method against fresh frozen human tissue sections, YBB 190 reacted with malignant cells in 26 of 28 epithelial cancers and with normal epithelia in 11 different benign tissues. Preliminary western blot antigen characterization indicated that YBB 190 recognizes cytokeratin intermediate filaments, or a protein that is closely associated with cytokeratins. These data indicate that B cells with specificity for intermediate filaments are present in tumor draining lymph nodes. Our findings provide insights into the nature of potential autoimmune responses in cancer patients and suggest that improved tumor directed sensitization procedures may be required to more effectively utilize lymphocytes from tumor draining lymph nodes to generate therapeutically useful human MAbs to TAAs.

Generation of therapeutic T lymphocytes from tumor-bearing mice by in vitro sensitization. Culture requirements and characterization of immunologic specificity.

We have previously established an in vitro sensitization (IVS) procedure with which lymphocytes from tumor-bearing mice could be expanded and sensitized to acquire antitumor reactivity capable of mediating the regression of established pulmonary metastases from the weakly immunogenic MCA 105 murine sarcoma. Culture conditions required for the optimal generation of therapeutic effector cells were evaluated in the current study. Generation of effector cells by IVS required stimulation by intact tumor cells. Tumor cells killed by heat or disrupted by sonication were ineffective, but the antigenicity of tumor cells was not affected by gamma-irradiation. Long term established tumor cell lines could also serve as antigenic stimulator cells albeit with lower efficiency than fresh tumor cells. IL-2 was essential for cellular proliferation during IVS. The concentration of 1000 U/ml of IL-2 also induced nonspecific lymphokine-activated killer (LAK) activity. However, cytotoxic cells were generated during IVS in response to a broad range of IL-2 concentrations. At low IL-2 concentrations (2 to 10 U/ml), IVS cells were generated which displayed little or no LAK activity, had a greater therapeutic efficacy than those generated with high concentrations of IL-2 (100 to 1000 U/ml). Despite having high LAK activity, IVS cells, from cultures where IL-2 was added 3 or more days after initiation, had no therapeutic effect. Thus, the generation of therapeutic cells occurred independently of LAK cell production. Adoptive immunotherapy with IVS cells from MCA 105 tumor-bearing mice demonstrated cross-reactivity with the immunologically distinct MCA 106 but not the nonimmunogenic MCA 102 tumor. In contrast, IVS cells from MCA 106 tumor-bearing mice exhibited specific in vivo reactivity. In vitro cytotoxicity analyses revealed that IVS cells from MCA 105 and MCA 106 tumor-bearing mice were able to lyse both MCA 105 and MCA 106 target cells, but the reactivity toward inoculating tumors was highest. Considering previous findings that the MCA 105 and MCA 106 sarcomas possessed distinct tumor-specific transplantation Ag, the cross-reactivity observed in this study suggests that the immune response during progressive tumor growth may be different from that elicited in response to active immunization.

Restriction of cell lysis by homologous complement: I. An analysis of membrane attack complex formation on target membranes

The hemolytic efficiency and binding of C9 to homologous and heterologous erythrocytes was evaluated by using a standardized passive sensitization procedure to prepare antigen- and antibody-coated erythrocytes (EA) and human serum for lysis. Heterologous bovine EA were readily lysed by human serum, whereas human EA were quite resistant to lysis. Human EA bound as many C8 and C9 molecules per cell as bovine EA when incubated under identical conditions, but four times as much bound C9 was required to lyse an equal number of human EA compared with bovine EA. The susceptibility of human erythrocytes did not increase when increased volumes of undiluted human serum were used although C9 binding increased to as much as 100,000 molecules per cell. Sodium dodecyl sulfate-resistant polymerized C9 (poly(C9)) was detected on both lysed ghosts and unlysed EA bearing complement proteins C1 through C9 (EAC1–9) after incubation with undiluted human serum; however, the ratio of poly(C9) to monomeric C9 was higher on unlysed cells than on ghosts. Although bovine and human EA bound equal amounts of human C9 at the end point, the rate of lysis and C9 uptake was slower on homologous cells. The rate-limiting step occurred before C9 binding and lysis because the rates of lysis and C9 binding were equal on homologous and heterologous EAC1–8 targets, but the extent of lysis of homologous cells was still lower than lysis of heterologous cells. Human erythrocytes lose restriction against homologous hemolysis during storage in autologous plasma or in isotonic buffers.

Restriction of Cell Lysis by Homologous Complement: I. An Analysis of Membrane Attack Complex Formation on Target Membranes

The hemolytic efficiency and binding of C9 to homologous and heterologous erythrocytes was evaluated by using a standardized passive sensitization procedure to prepare antigen- and antibody-coated erythrocytes (EA) and human serum for lysis. Heterologous bovine EA were readily lysed by human serum, whereas human EA were quite resistant to lysis. Human EA bound as many C8 and C9 molecules per cell as bovine EA when incubated under identical conditions, but four times as much bound C9 was required to lyse an equal number of human EA compared with bovine EA. The susceptibility of human erythrocytes did not increase when increased volumes of undiluted human serum were used although C9 binding increased to as much as 100,000 molecules per cell. Sodium dodecyl sulfate-resistant polymerized C9 (poly(C9)) was detected on both lysed ghosts and unlysed EA bearing complement proteins C1 through C9 (EAC1-9) after incubation with undiluted human serum; however, the ratio of poly(C9) to monomeric C9 was higher on unlysed cells than on ghosts. Although bovine and human EA bound equal amounts of human C9 at the end point, the rate of lysis and C9 uptake was slower on homologous cells. The rate-limiting step occurred before C9 binding and lysis because the rates of lysis and C9 binding were equal on homologous and heterologous EAC1-8 targets, but the extent of lysis of homologous cells was still lower than lysis of heterologous cells. Human erythrocytes lose restriction against homologous hemolysis during storage in autologous plasma or in isotonic buffers.

Different ability of trifluoperazine to inhibit agonist-induced contraction of lung parenchyma strips from control and sensitized guinea-pigs.

There is increasing interest in the therapeutic potential of calcium antagonists in asthma. Among them the use of calmodulin antagonists deserves consideration. In the present work the effect of trifluoperazine on contractions generated by different mechanisms (CaCl2, KCl, acetylcholine, histamine and 5-hydroxytryptamine) in lung parenchyma strip isolated from control and actively sensitized guinea-pigs has been studied. Trifluoperazine produced both in unsensitized and sensitized lung strips, a concentration-dependent, right, downward displacement of the concentration-response curves to the agonists used, although the sensitization procedure resulted in a potentiation in the ability of trifluoperazine to inhibit agonist-induced contractions. The basis for this greater potency of trifluoperazine in sensitized tissues remains to be elucidated but raises attention to the future use of selective calmodulin antagonists in the management of asthma.

SOCRATES: a highly efficient automatic test pattern generation system

An automatic test pattern generation system, SOCRATES, is presented. SOCRATES includes several novel concepts and techniques that significantly improve and accelerate the automatic test pattern generation process for combinational and scan-based circuits. Based on the FAN algorithm, improved implication, sensitization, and multiple backtrace procedures are described. The application of these techniques leads to a considerable reduction of the number of backtrackings and an earlier recognition of conflicts and redundancies. Several experiments using a set of combinational benchmark circuits demonstrate the efficiency of SOCRATES and its cost-effectiveness, even in a workstation environment. >

Hapten-Specific Antibodies in Allergic Contact Dermatitis in the Guinea Pig

A guinea pig model was used to investigate the potential role of hapten-specific antibodies in allergic contact dermatitis. Hapten-specific antibodies of both the IgG1, IgG2 and IgM (sub)classes could be readily detected by ELISA in sera obtained after single or repeated exposure to the allergens 2,4-dinitrochlorobenzene (DNCB) or 4-ethoxymethylene-2-phenyloxazolone. Experiments in which animals were strongly boostered with Freund's complete adjuvant support previous reports that hapten-specific antibodies are able to transfer contact skin reactions with a delayed time course into naive recipients. In contrast, epicutaneous sensitization procedures never allowed transfer of such reactivity. Upon transfer of immune sera to previously sensitized animals, existing allergic contact dermatitis was unaffected, except for a distinct suppression of induration, but not erythema, in the DNCB system. In actively sensitized animals, antibody-related suppression of induration was never observed. Hapten-specific hyposensitivity, as induced by repeated epicutaneous exposure, was also not related to circulating antibody levels. Our findings do not support the view that hapten-specific antibodies should be reconsidered as playing a potentially important role in allergic contact dermatitis.

Dermal Sensitization Study in Hairless Guinea Pigs with Dinitrochlorobenzene and Ethyl Aminobenzoate

This study was designed to investigate the use of adult female hairless guinea pigs, bred at Charles River Laboratories, Inc. (CRL-IAF(HA)BR), as a model for dermal sensitization studies. These animals are euthymic and hairless except for continuous hair growth at the nose and feet. A modified Magnusson and Kligman dermal sensitization procedure was used. One group of Hartley and one group of hairless female guinea pigs were induced with 20% ethyl aminobenzoate (benzocaine) or 0.5% dinitrochloro-benzene (DNCB). Animals were first challenged with 10% benzocaine or 0.5% DNCB. A second challenge was conducted using 5% benzocaine and 0.1% DNCB. Compared with the Hartley guinea pigs, the hairless guinea pigs were statistically significantly more sensitive to the irritating effects of the compounds (grossly and histologically). No statistically significant differences occurred between the strains in the incidence of sensitization to DNCB or benzocaine when corrected for baseline response. Advantages of the hairless guinea pigs included easier viewing of weak responses, fewer lesions due to the taping and shaving process, and fewer patches removed accidentally during the 24 hr exposure periods.

The effects of covert sensitization on preference for sexual stimuli: A preliminary analogue experiment

Although covert sensitization is a widely and diversely employed clinical technique, there is no generally accepted conceptual guideline for its implementation. Consequently, there is considerable variability in the way covert sensitization procedures are employed, which may account for the reported inconsistency in its clinical effectiveness. The present study is an analogue experimental test of a conceptual account of covert sensitization that is based upon classical conditioning. The classical conditioning procedure is viewed as affecting operant target behaviors by altering the reinforcer effectiveness of target stimuli. This was explicitly tested by examining the effects of covert sensitization on subjects' preference for sexual stimuli in an operant choice paradigm. The results support the conceptual account.

Basophil sensitivity and reactivity to monoclonal anti-human IgE afterin vitro sensitization with human myeloma IgE

Leucocytes from human peripheral blood were acid eluted and sensitized in vitro with increasing concentrations of radiolabelled myeloma IgE. This sensitization step was performed with or without 30% IgE depleted serum. After the IgE binding, cells were washed and submitted to a challenge with monoclonal anti-IgE for the determination of the cellular sensitivity and reactivity in a histamine release assay. A sample of each of the sensitized cells was analyzed for its radioactivity and the number of basophils quantified, thus allowing the determination of the mean number of IgE molecules per basophil. Raising the IgE concentrations in the sensitization procedure led to an increase of the IgE on the basophil membrane, and to a concomitant elevation of the cell sensitivity. The presence of serum during the binding of IgE onto the cells lowers slightly the binding of IgE to the basophils but decreases strongly the cellular reactivity.

Possible Functional Impairment of Langerhans' Cells in Vitiliginous Skin

• We used patch testing to compare the ability to elicit contact sensitivity to dinitrochlorobenzene (DNCB) of uninvolved with vitiliginous skin of 31 patients with vitiligo. The induction of DNCB contact sensitivity was possible in the vitiliginous skin in the same way as in normal skin. The DNCB contact sensitivity reactions, however, were generally diminished in vitiliginous skin, although the number of cases showing similar DNCB contact reactivity between normal and vitiliginous skin increased when the sensitization procedure was performed in vitiliginous skin instead of normal skin. On the other hand, delayed skin reactions to intradermally injected<i>Candida albicans</i>antigen were not suppressed in vitiliginous skin. The number of Langerhans' cells was not decreased in vitiliginous skin as compared with that of normal skin. The epidermal cells derived from vitiligonous skin, however, tended to show a lower stimulatory effect in the allogeneic mixed skin cell lymphocyte culture reaction than those from normal skin. These results suggest a possibility of functional impairment of Langerhans' cells in vitiliginous skin. (<i>Arch Dermatol</i>1987;123:51-54)

Possible functional impairment of Langerhans' cells in vitiliginous skin. Reduced ability to elicit dinitrochlorobenzene contact sensitivity reaction and decreased stimulatory effect in the allogeneic mixed skin cell lymphocyte culture reaction

We used patch testing to compare the ability to elicit contact sensitivity to dinitrochlorobenzene (DNCB) of uninvolved with vitiliginous skin of 31 patients with vitiligo. The induction of DNCB contact sensitivity was possible in the vitiliginous skin in the same way as in normal skin. The DNCB contact sensitivity reactions, however, were generally diminished in vitiliginous skin, although the number of cases showing similar DNCB contact reactivity between normal and vitiliginous skin increased when the sensitization procedure was performed in vitiliginous skin instead of normal skin. On the other hand, delayed skin reactions to intradermally injected Candida albicans antigen were not suppressed in vitiliginous skin. The number of Langerhans' cells was not decreased in vitiliginous skin as compared with that of normal skin. The epidermal cells derived from vitiliginous skin, however, tended to show a lower stimulatory effect in the allogeneic mixed skin cell lymphocyte culture reaction than those from normal skin. These results suggest a possibility of functional impairment of Langerhans' cells in vitiliginous skin.