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PubMed2001

Inhibition of endothelial cell proliferation and tumor-induced angiogenesis by pentoxifylline.

PURPOSE: In this study we investigated the effect of pentoxifylline (PTX) on tumor-induced neovascularization as well as on different steps involved in the angiogenic process. METHODS: To assess angiogenesis inhibition. we injected intradermally (i.d.) 10 B16-F10 melanoma cells into C57BL/6J mice which were subsequently intraperitoneally (i.p.) inoculated with PTX or saline. On day 7 the number of blood vessels converging to the remnant of injected material was counted and the volumes of incipient tumors were calculated in each case. In vitro growth inhibition by PTX was evaluated in two different cell lines of endothelial origin and in human umbilical vein endothelial cells. Motility assays, as well as zymographic assays carried out to analyze gelatinolytic metalloproteinases and urokinase-type plasminogen activator, were performed in one of the endothelial cell lines. RESULTS: A significant inhibition of tumor-induced angiogenesis was observed in C57B1/6 mice i.p. inoculated with PTX, that paralleled reduced incipient tumor volumes. The endothelial cells derived from different sources were inhibited in a dose-response manner by PTX in vitro. Non-cytotoxic PTX concentrations assayed in one of the endothelial cell lines did not inhibit its in vitro cell motility nor its gelatinase secretion, but its low molecular weight urokinase-type plasminogen activator expression. CONCLUSIONS: Our findings suggest that the inhibitory effect of PTX on tumor angiogenesis is related to antiproliferative action on endothelial cells, as well as to down regulation of u-PA secreted by them.

Angiogenesis Inhibitors↗
PubMedDate not supplied

Toxic properties of the Mycoplasma arthritidis ISR-1 membrane.

Isolated membranes of Mycoplasma arthritidis ISR-1 possess toxic properties for rats, mice and chicken embryos. Reactions are dose-dependent. By intravenous injection of 20 mg of membrane protein, a lethal toxicity syndrome resembling shock is induced in Sprague-Dawley rats of 100 g body weight. Mice of approximately 20-g body weight show the same syndrome by intravenous injection of 15 mg of membrane protein. The lethal toxicity for chicken embryos increases from 10 to 80% after injection of 0.3 to 1.5 mg of membrane protein. The LD50 in chicken embryos was found to be 0.5 mg membrane protein. After administration of 10-15 mg of membrane protein, rats showed an increase in temperature from 38 to 41 degrees C within 5 h. Because of the difficulty in measuring the temperature in mice, loss of body weight was taken as the criterion for toxicity. Body weight was reduced up to 16% within 1 day after intravenous injection of 500 micrograms of membrane protein per g of body weight. For sheep red blood cells, M. arthritidis ISR-1 membranes were haemolytic in concentrations of 4 mg of membrane protein and higher. Intradermal injection of 1 mg of membrane protein into guinea-pigs resulted in red swelling reactions measuring approximately 10 mm in diameter 10 h after injection. For foetal rat skin fibroblasts, M. arthritidis ISR-1 membranes were toxic in concentrations from 1 micrograms (3H-uridine incorporation), 10 micrograms (14C-leucine incorporation) and 100 micrograms (3H-thymidine incorporation) of membrane protein.

Animals↗
PubMed1962

The effect of bacterial endotoxin on the newborn guinea pig.

Newborn guinea pigs (less than 24 hours old) are highly susceptible to the lethal effect of endotoxin and susceptibility decreases with age. The vulnerability to endotoxin has not been attributed to hypofunction of either the adrenal gland or the reticuloendothelial system of the newborn, since prior injection of corticosteroids provides only partial protection to endotoxin and newborn guinea pigs can efficiently remove colloidal substances from the circulation. In contrast to adults, newborns do not develop a delayed inflammatory reaction following intradermal injection of endotoxin, and after intravenous challenge frequently fail to display neutropenia and sustained fever.

Antitoxins↗
PubMed2002

Lymphatic pathways of the upper medial quadrant of the breast in healthy women: radiotracer study of the sentinel lymph node.

This study examined the lymphatic drainage after injection of a radiotracer into the upper medial quadrant of the breast in healthy women. Most studies of lymphatic pathways of the breast have been performed in patients with breast cancer and concentrate on the upper lateral quadrant of the breast because of the high incidence of carcinoma at this site. The lymphatic drainage pathways of the medial half of the breast, however, has been less studied. A radiotracer (Tc-99m human serum albumin nanocolloid or HSA) was injected intradermally into the upper medial quadrant of the right breast in 12 healthy women. Dermal markers were placed at the middle of the clavicle, the axilla and at the jugular incisura. Three minutes after injection a static image of the injection site was made with a scintillation camera (Multispect 2 Gamma Camera System) over 20 seconds. After nine minutes, local soft massage was instituted at the injection site for 6 minutes. Fifteen minutes after injection, a graphic scintigraphic image was made of both breasts and axillae over 22 minutes. After this interval, three or four static images were made for a few seconds to locate the sentinel lymph node as related to the injection site. A sentinel lymph node (lymphatic pathway) in the axilla was visualized in 11 subjects (91.9%) and was undetected in one subject (8.3%). The radiotracer migrated in all patients (100% ) towards the ipsilateral axilla. In 9 subjects, the sentinel lymph node was visualized 15 minutes after injection, whereas in 2 subjects it appeared within an hour.

Adult↗
PubMed1999

Epinephrine produces a beta-adrenergic receptor-mediated mechanical hyperalgesia and in vitro sensitization of rat nociceptors.

Hyperalgesic and nociceptor sensitizing effects mediated by the beta-adrenergic receptor were evaluated in the rat. Intradermal injection of epinephrine, the major endogenous ligand for the beta-adrenergic receptor, into the dorsum of the hindpaw of the rat produced a dose-dependent mechanical hyperalgesia, quantified by the Randall-Selitto paw-withdrawal test. Epinephrine-induced hyperalgesia was attenuated significantly by intradermal pretreatment with propranolol, a beta-adrenergic receptor antagonist, but not by phentolamine, an alpha-adrenergic receptor antagonist. Epinephrine-induced hyperalgesia developed rapidly; it was statistically significant by 2 min after injection, reached a maximum effect within 5 min, and lasted 2 h. Injection of a more beta-adrenergic receptor-selective agonist, isoproterenol, also produced dose-dependent hyperalgesia, which was attenuated by propranolol but not phentolamine. Epinephrine-induced hyperalgesia was not affected by indomethacin, an inhibitor of cyclo-oxygenase, or by surgical sympathectomy. It was attenuated significantly by inhibitors of the adenosine 3',5'-cyclic monophosphate signaling pathway (the adenylyl cyclase inhibitor, SQ 22536, and the protein kinase A inhibitors, Rp-adenosine 3',5'-cyclic monophosphate and WIPTIDE), inhibitors of the protein kinase C signaling pathway (chelerythrine and bisindolylmaleimide) and a mu-opioid receptor agonist DAMGO ([D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin). Consistent with the hypothesis that epinephrine produces hyperalgesia by a direct action on primary afferent nociceptors, it was found to sensitize small-diameter dorsal root ganglion neurons in culture, i. e., to produce an increase in number of spikes and a decrease in latency to firing during a ramped depolarizing stimulus. These effects were blocked by propranolol. Furthermore epinephrine, like several other direct-acting hyperalgesic agents, caused a potentiation of tetrodotoxin-resistant sodium current, an effect that was abolished by Rp-adenosine 3',5'-cyclic monophosphate and significantly attenuated by bisindolylmaleimide. Isoproterenol also potentiated tetrodotoxin-resistant sodium current. In conclusion, epinephrine produces cutaneous mechanical hyperalgesia and sensitizes cultured dorsal root ganglion neurons in the absence of nerve injury via an action at a beta-adrenergic receptor. These effects of epinephrine are mediated by both the protein kinase A and protein kinase C second-messenger pathways.

Analysis of Variance↗
PubMed1996

Pharmacological characterization of novel tissue kallikrein inhibitors in vivo.

In this study we have investigated the effect of novel tissue kallikreins on the plasma protein exudation induced by porcine pancreatic kallikrein (PPK) in the rabbit skin in vivo. The tissue kallikrein inhibitors here described were synthesized based on analogues of peptide substrates for tissue kallikreins. The intradermal injection of PPK and rabbit urinary kallikrein, but not of rabbit plasma kallikrein, significantly increased the microvascular permeability leading to local oedema formation in the rabbit skin. At the dose of 3-200 nmol/site, the intradermal co-administration of the tissue kallikrein inhibitors Bz-F-F-S-R-EDDnp (Ki = 0.1 microM; ESP5), PAC-F-S-R-EDDnp (Ki = 0.7 microM; ESP6), Bz-F-F-A-P-R-NH2 (Ki = 7.8 microM; ESP8), PAC-F-F-R-P-R-NH2 (Ki = 0.3 microM; ESP9) and Bz-F-F-S-R-NH2 (Ki = 0.3 microM; ESP11) dose-dependently inhibited the plasma protein exudation induced by PPK. The most potent compound was ESP6 (IC25 = 7.8 nmol/site) followed by ESP5 (IC25 = 14.2 nmol/site), ESP8 (IC25 = 25 nmol/site), ESP9 (IC25 = 30 nmol/site) and ESP11 (IC25 = 50.4 nmol/site). The compounds Bz-F-F-R-P-R-NH2 (Ki = 0.5 microM; ESP1), Bz-F-F-pNa (Ki = 0.4 microM; ESP3), Bz-F(NH2)-F-R-P-R-NH2 (Ki = 1.1 microM; ESP7) and Bz-F-F-S-P-R-NH2 (Ki = 4.6 microM; ESP10) had no significant effect on the PPK-induced plasma protein exudation in doses up to 200 nmol/site. ESP6 also inhibited the PPK-induced plasma protein exudation when administered systemically. This compound may constitute a useful tool to further investigate both the physiological and pathological role of tissue kallikreins.

Animals↗
PubMed1994

Mild hypothermia during halothane-induced anesthesia decreases resistance to Staphylococcus aureus dermal infection in guinea pigs.

Because various immune functions are impaired at temperatures only 1 degrees to 3 degrees C less than normal, we tested the hypothesis that mild hypothermia during anesthesia impairs resistance to dermal infections. Guinea pigs were anesthetized for 6 hours with 1% inspired halothane. Their core temperatures were maintained at either 39 degrees C (normal for guinea pigs, n = 12) or 36 degrees C (n = 12). Two hours after induction of anesthesia, three doses each of Staphylococcus aureus (10(8), 10(7), and 10(6) organisms) were injected intradermally at nine sites on each animal's back. Core temperatures were not controlled after recovery from the anesthetic, and animals in each group were maintained in the same environment. Four days after anesthesia, each injection site was excised to obtain a count of viable bacteria. Subcutaneous oxygen partial pressure values, averaged over time, were 53 +/- 3 mm Hg (mean +/- SEM) in the hypothermic group and 62 +/- 4 mm Hg in the normothermic group (p = 0.06). Capillary perfusion, as assessed by laser Doppler flowmetry, was comparable in the two groups. One day after injection of 10(8) bacteria, the area of induration was 89 +/- 11 mm(2) in the hypothermic group but only 61 +/- 6 mm(2) in the normothermic group (p < 0.05). On postanesthetic day 4, the area of induration was 72 +/- 6 and 59 +/- 6 mm(2) in the hypothermic and normothermic groups, respectively (p > 0.05). After inoculation with 10(8) bacteria, the fraction recovered was 1.0 +/- 0.2 in the hypothermic groups and 0.6 +/- 0.2 in the normothermic group (p < 0.05). After inoculation with 10(7) and 10(6) bacteria, the fraction recovered was less than 0.2, and no difference was found between the hypothermic and normothermic animals. Thus mild hypothermia during halothane-induced anesthesia slightly impairs resistance to dermal infection.

Journal Article↗
PubMed2000

Aero-allergens in canine atopic dermatitis in southeastern Australia based on 1000 intradermal skin tests.

OBJECTIVE: To determine the most relevant aero-allergens involved in canine atopic dermatitis in southeastern Australia and provide information about these aero-allergens to the general practitioner. PROCEDURE: Dogs presented to the Animal Skin & Allergy Clinic with history and clinical signs of atopic dermatitis were injected intradermally with 38 different allergens and negative and positive control. Intradermal skin tests in 1000 dogs were retrospectively evaluated. RESULTS: One third of all patients reacted to the house dust mite Dermatophagoides farinae. Allergens reacting in more than 15% of the patients were wheat (Triticum aestivum), sweet vernal (Anthoxanthum odoratum), English couch (Agropyron repens), yellow dock (Rumex crispus), Mexican tea (Chenopodium ambrosioides), plantain (Plantago lanceolata), melaleuca (Melaleuca quinquenervia) and peppercorn (Schimus spp). CONCLUSION: House dust mites are the most common allergens in canine atopic dermatitis in southeastern Australia and D farinae is involved most frequently. However, a number of grass, weed and tree pollens also are involved regularly.

Aerosols↗
PubMed1980

Reaginic (type 1 anaphylactic) antibodies produced by calves in response to Hypoderma larvae.

Reaginic antibody production by Hypoderma lineatum and H bovis larval antigens were evaluated in three calves using passive cutaneous anaphylaxis (PCA). Two calves were sensitised with soluble extract of H lineatum larvae and a third was injected with 43 hatching H bovis larvae. Blood serum taken from the calves was injected intradermally in 0.1 ml volumes into three test calves. Sera from the calves sensitised with hypoderma extract produced positive PCA reactions in all three calves with maximum titres of 1:8. Sera from the calf injected with living larvae caused positive PCA reactions in two of the three test calves, the maximum titre being 1:4. The results indicate that the calves produced reaginic antibody to H bovis and H lineatum, although serum concentrations of the antibody were relatively low.

Animals↗
PubMed1979

Enhanced macrophage tumoricidal activity and tumor suppression or regression caused by heat-killed Candida albicans.

The growth of line-10 hepatoma in male Sewall Wright strain 2 guinea pigs was totally suppressed when tumor cells were mixed with heat-killed Candida albicans. In a significant number of animals, injection of C. albicans into established tumors 10-12 mm in diameter caused complete, rapid tumor regression. Guinea pigs whose tumors regressed or were suppressed as a result of injection of C. albicans rejected subsequent challenges at distant sites with the line-10 hepatoma, which indicated the development of systemic immunity to the tumor. Untreated control guinea pigs had positive delayed hypersensitivity reactions to intradermally injected C. albicans, which suggested prior natural exposure of the animals to C. albicans antigens. Peritoneal macrophages from mice that had received ip injections of phosphate-buffered saline (PBS) or C. albicans were not cytocidal for mouse 3T12 tumor cells in vitro. However, macrophages from the mice given injections of C. albicans, unlike those from mice given PBS, were markedly tumoricidal in the presence of 1 ng or more endotoxin/ml in vitro. These results demonstrated that heat-killed C. albicans, when inoculated into the peritoneal cavity, increased the tumoricidal potential of peritoneal macrophages.

Animals↗
PubMed1996

Absence of skin sensitivity to oxides of aluminium, silicon, titanium or zirconium in patients with Crohn's disease.

BACKGROUND: Some metallic compounds, especially of zirconium, can cause cell mediated granulomatous inflammation of the skin. Pigment granules containing compounds of aluminium, silicon, and titanium have been observed within macrophages in the wall of the small intestine in health and in Crohn's disease. Zirconium compounds can be ingested in toothpaste. AIM: To determine in a pilot study if granulomatous sensitivity can be detected to compounds of these metals or silicon after injection into the skin of patients with Crohn's disease. SUBJECTS: Eight patients with Crohn's disease known to have had granulomata in the intestine and not currently treated with corticosteroids, and two healthy controls. METHOD: Two intradermal injections each of 0.1 ml of a 0.02% suspension of one of the compounds made in the abdominal wall of each subject. The site was marked and full thickness skin biopsy performed six weeks later. RESULT: A foreign body granuloma was observed on histological examination of two biopsy specimens but no evidence of a cell mediated response in any subject. CONCLUSION: No support was found for the hypothesis that Crohn's disease is due to a specific sensitivity to ingested metallic or silicon compounds.

Aluminum Oxide↗
PubMed2005

Enzymatic characterization, antigenic cross-reactivity and neutralization of dermonecrotic activity of five Loxosceles spider venoms of medical importance in the Americas.

Loxosceles spiders have a wide distribution in the temperate and tropical regions of the world. Loxoscelism is characterized by necrotic skin ulceration at the bite site and, less commonly, a systemic illness that may be fatal. The purpose of this study was to characterize and compare aspects of the major medically important Loxosceles spider venoms in a standardized manner, particularly considering their neutralization by two Brazilian antivenoms. By SDS-PAGE (12% acrylamide), Loxosceles deserta, Loxosceles gaucho, Loxosceles intermedia, Loxosceles laeta and Loxosceles reclusa venoms had similar electrophoretic profiles, with the major protein bands of 32-35 kDa. All venoms exhibited gelatinolytic, caseinolytic and fibrinogenolytic activities in vitro with a large array of proteases, mainly between 18.1 and 31.8 kDa. Most of these enzymes were metalloproteases as this activity was abolished by 1,10-phenanthroline. Hyaluronidase activity was detected in a protein band of approximately 44 kDa in all venoms. Sphingomyelinase activity was demonstrated in all five venoms. Antigenic cross-reactivity, by Western blotting, was also observed among all venoms studied using commercial equine antivenoms produced in Brazil (Institute Butantan and CPPI). These antivenoms recognized mainly components between 25 and 40 kDa in all venoms with several minor components of >89 kDa. Strong cross-reactivity was also seen among all venoms through the ELISA technique (titre range: 64,000-512,000). All venoms (5 microg doses) induced a similar local reaction when injected intradermally into the flank of rabbits, demonstrating dermonecrosis, hemorrhage, vasoconstriction, edema, and erythema. However, no reaction was observed when each venom was pre-incubated (1 h, 37 degrees C) with Brazilian commercial sera prior to injection. The antivenoms also abolished the sphingomyelinase activity in vitro, suggesting the venoms of the major medically important Loxosceles spider species have generally similar toxic and enzymatic characteristics. Thus, as Brazilian commercial antivenoms are able to neutralize the dermonecrosis induced by Loxosceles venoms of diverse geographical origin, clinical studies should be undertaken on the potential for a single global Loxosceles antivenom.

Animals↗
PubMed1997

Intradermal antigen tests and the Koebner phenomenon in psoriasis.

BACKGROUND: Psoriasis is one of several dermatologic conditions in which nonspecific irritation may elicit the disease where it was not previously present. In this study we aimed to assess the cutaneous cellular immune reaction with intradermal antigen tests and the relation between Koebner's phenomenon and intradermal antigens. METHODS: Thirty psoriasis patients and 20 control subjects were tested with 0.1 mL intradermal injections of purified protein derivative (PPD), Candida (C), mumps (M), mixed respiratory vaccine (MRV), and saline control solutions. Koebner status was also determined in the psoriatic patients. Injection sites were evaluated at 72 h and on the eighth, 12th, 16th, and 20th days for erythema, induration, and local development of psoriasis. RESULTS: Two patients were Koebner positive and developed psoriasis at all five injection sites. However, local psoriasis development was observed at one or more injection sites in five Koebner-negative patients. In addition, intensity of delayed hypersensitivity reaction and resolution times demonstrate no significant difference between psoriatic and nonpsoriatic subjects statistically (P > 0.05). CONCLUSIONS: These findings may indicate that intradermal antigens used in this study were more effective in inducing the Koebner phenomenon than injury alone. Furthermore, we observed that there is no meaningful difference between psoriatic and nonpsoriatic subjects in developing cutaneous cellular immune reactions.

Adult↗
PubMed2005

Intradermal testing with the storage mite Tyrophagus putrescentiae in normal dogs and dogs with atopic dermatitis in Colorado.

The purpose of this study was to evaluate reactions to intradermal injections of Tyrophagus putrescentiae extract in healthy dogs and dogs with atopic dermatitis and to compare the prevalence of positive reactions in the two groups. Twenty-one healthy dogs and 26 atopic dogs were tested intradermally with T. putrescentiae extract at 1000, 500, 250, 125, 63, 32 and 16 PNU/mL. Reactions were evaluated objectively and subjectively. A Mann-Whitney test was used to determine differences in grade of reaction to storage mites between healthy dogs and dogs with atopic dermatitis. Positive reactions to storage mite extract were most common at 1000 PNU/mL with approximately one third of normal and atopic dogs showing a positive reaction to T. putrescentiae. There was no significant difference in the incidence of positive reactions between normal and atopic dogs for any of the Tyrophagus extract concentrations.

Acaridae↗
PubMed1995

Prevention and reversal of superantigen-induced anergy by contact allergen exposure.

The superantigen Staphylococcal enterotoxin B (SEB) and the contact allergen 2,4-dinitrofluorbenzene (DNFB) both react with V beta 8+ T-cells delivering distinct signals. Pre-treatment with DNFB painted onto the same skin site where SEB was to be injected, prevented the induction of anergy in V beta + T-cells that was otherwise induced after SEB had been injected intradermally over a period of 2 weeks. Application of the irritant sodium dodecyl sulfate (SDS) instead of DNFB did not exert this effect. Application of DNFB at a site distant from the site where SEB was injected resulted in a much weaker inhibitory influence on the induction of anergy by SEB. Established anergy of V beta 8+ T-cells (proliferative non-responsiveness to SEB in vitro that could be overcome by addition of exogenous interleukin 2 (IL-2)) could be largely reversed by repeated cutaneous exposure to DNFB painted to the site where SEB had been injected before. The moderate decrease of V beta 8+ T-cells normally induced by SEB-treatment was also partially prevented by DNFB pre-treatment. The data indicate the importance of the sequence of signals delivered to T cells and the plasticity of the responsiveness of this cell type.

Administration, Topical↗
PubMed2001

Intradermal testing in healthy horses and horses with chronic obstructive pulmonary disease, recurrent urticaria, or allergic dermatitis.

OBJECTIVE: To compare responses to a variety of intradermally injected allergens among healthy horses and horses with chronic obstructive pulmonary disease (COPD), recurrent urticaria (RU), and atopic dermatitis-insect hypersensitivity (allergic dermatitis [AD]). DESIGN: Case-control study. ANIMALS: 86 horses. PROCEDURE: Results of intradermal testing for horses with COPD, RU, or AD were compared with results for healthy horses. RESULTS: Compared with healthy horses, horses with COPD, RU, and AD were significantly more likely to have positive (> or = 3+) reactions to intradermal allergens (molds, weeds, trees, grasses-crops, and insects) 30 minutes (immediate reaction), 4 hours (late-phase reactions), and 24 hours (delayed-phase reactions) after exposure. In addition, diseased horses reacted to a significantly higher number of allergens in each allergen group than did healthy horses. CONCLUSIONS AND CLINICAL RELEVANCE: Reactions to individual allergens should not be used to determine that horses have hypersensitivity. Overall patterns of reactivity to intradermal allergens may be helpful in management when used in conjunction with a compatible history and evidence of potential exposure to allergens in horses with conditions associated with hypersensitivity to environmental allergens.

Allergens↗
PubMed1989

Interferon therapy for condylomatous vulvitis.

During a 3-year period, 30 patients were referred for symptoms of vulvar pain characteristic of the vulvar vestibulitis syndrome. Colposcopic examination with a blue filter and pathologic biopsy revealed evidence of papillomavirus in 17 patients. Interferon alpha-2b recombinant was injected intradermally into the vestibule in a specific pattern three times weekly for 4 weeks. Fifteen women responded favorably with total absence of vulvar pain. Five women reported flu-like symptoms as a result of the injections. Patients without evidence of papillomavirus failed to respond to interferon therapy. Women with evidence of vulvar papillomavirus failed to respond to placebo but did respond to retreatment with interferon; vulvar biopsy specimens after therapy were negative. Interferon alpha-2b recombinant appears to offer an inexpensive, safe alternative to the more traumatic therapies currently recommended in the specific subset of vulvar vestibulitis patients in whom papillomavirus can be confirmed.

Dyspareunia↗
PubMed1982

Immunological and pharmacological characterization of poly-DL-alanyl-modified Erwinia carotovora L-asparaginase.

The covalent attachment of poly-DL-alanine peptides to lysyl residues on the surface of Erwinia carotovora L-asparaginase has produced a modified enzyme which is much less immunogenic in mice and demonstrates 100-fold longer plasma half-life in the rhesus monkey. Immunogenic responses towards both the immunoglobulin G (IgG) and immunoglobulin E (IgE) antibody subclasses were evaluated in C57BL x DBA/2 F1 mice exposed to 250 rads of whole-body irradiation 4 hr prior to immunization with 5-diazo-4-oxynorvaline-inactivated native and modified L-asparaginase in complete Freund's adjuvant. Under these immunologically stressful conditions, the native enzyme evoked an IgE and IgG response which could be further amplified by a secondary immunization, whereas the modified enzyme evoked no IgE or IgG response even after a tertiary immunization. In experiments mimicking an intensive therapeutic schedule, whereby two groups of mice were given weekly injections of 5 to 10 units of either native or modified asparaginase for up to 14 weeks, neither enzyme form evoked a significant IgE response, and only the mice given injections of the native enzyme produced an IgG response. In a preliminary patient study, skin testing of a child who had shown an allergic reaction to the native enzyme resulted in a negative response after an intradermal injection of the modified enzyme, whereas a wheal and flare reaction was observed to both the native enzyme and a histamine control. All of these results suggest that the modified enzyme should show a definite reduction in immunological reactions associated with L-asparaginase treatment of childhood leukemia.

Allergens↗