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    The Journal of Investigative Dermatology(1952) 18, 403418; doi:10.1038/jid.1952.48

    The Insect Bite Reaction

    I. The Mechanism1

    This investigation was supported by a research grant from the Division of ResearchGrants and Fellowships of the National Institutes of Health, United States Public HealthService.

    Parts of the study were done through Dr. W. V. King, in Charge, United StatesDepartment of Agriculture, Agricultural Research Administration, Bureau of Entomologyand Plant Quarantine, Orlando, Florida.

    Read before The Meeting of The Twelfth Annual Meeting of The Society for InvestigativeDermatology, Inc., Atlantic City, N.J., June 7 and 8, 1952.

    Leon Goldman MD, Patricia Johnson BS and James Ramsey MS

    1 From the Department of Dermatology and Syphilology of the College of Medicine of the University of Cincinnati.

    In addition to the clinical problems sometimes presented by the severe local, or morerarely, generalized reactions of sensitized persons to insect-bites, the feeding

    mechanisms of blood sucking insects, the nature of the lesions produced by their bites,and the subsequent reactions of the human host are of more than academic interestbecause of their bearing on the transmission and development of the parasites causing

    insect borne diseases. Thus the course of an insect-borne disease may be influenced bythese factors at any one of the three natural phases -that is, at the time when theparasite is taken up by the vector, at the time when it is deposited in the new host, and

    finally during the early stages of its subsequent development.77 These remarks by Prof.R. M. Gordon and W. Crewe (1) serve to introduce this review, primarily for thedermatologist, of the study of the mechanism of the insect bite. We felt that no detailedstudy of sensitivity to the bites of various arthropods or clinical investigations on humanskin of repellents and toxicants could be done without some prior attempts to study this

    insect bite reaction in man.

    From a study of the anatomy of the biting parts of some of the arthropods included inthe report, it seems to us that in general for the dermatologist, the biting mechanism in

    sequence can be classified as to: 1. whether or not the arthropod fastens itself securelyto the surface of the skin, a condition peculiar to slow feeders as it were; 2. whichportion of the apparatus is used to puncture the skin; 3. whether the actual puncture is a

    direct stab into or a biting of the skin; 4. what mechanisms may puncture or lacerate theblood vessel wall. This classification is shown in Table 1.

    It is not the purpose to review in detail the anatomy of the biting parts (2) of the variousinsects under study. These are depicted in a diagrammatic fashion in Figure 2. It isindicated by Gordon and Crewe that since observations during the actual process ofbiting are scanty and incomplete, it must be concluded that their (various authors on themechanism and effect of insect bites) interpretations and functions of the mouth-parts,although probably correct, are mainly conjectural (1). The mechanism, in brief, is

    thought to consist first in cutting 403 404 THE JOURNAL OF INVESTIGATIVEDERMATOLOGY or laceration or puncture of the skin by the insect, then the insertion ofthe proboscis through the wound, the injection of saliva, the probing for a blood vessel,

    the blood sucking either directly from the blood vessel or from a pool of blood (poolfeeding), and finally the withdrawal of the proboscis.

    http://www.nature.com/jid/journal/v18/n5/full/jid195248a.html#tlnote1http://www.nature.com/jid/journal/v18/n5/full/jid195248a.html#tlnote1http://www.nature.com/jid/journal/v18/n5/full/jid195248a.html#tlnote1
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    For the purpose of our investigation it was decided to attempt to limit the work to humanskin even though we realized the inherent and obvious difficulties of such a study.Various insects were therefore observed on normal skin especially on the extremities,back, and ears; also on various types of skin lesions. Because of the vast amount ofdetails necessary to evaluate the allergic reaction, this particular portion was made aseparate study under the direction of Evelyn Rockwell.

    The instrumentation in the study of the mechanism of the bite reaction included briefly:1. Microscopes A. With the stereo microscope of Zeiss observation of the insects on skinand the bite reactions.

    TABLE 1 General outline of the stages of some insect bites in human skin AEDES CIMEX

    PEDICULUS XENOPSYLLA AMBLYOMMA EUTROMBICULA (mosquito) (bedbug) (louse)(flea) (tick) (chigger) A. Skin attachment..

    None None By means of Only superfi- By means of Chelicerae im-short, cial. Maxil-hypos

    tome bedded in toothed, lary lobes with rever-epidermis evertible hold steady siblebarbs.

    haustellum position B. Skin puncture ....

    Serrate tip- Serrate tip- Slender, sty- Blade-like Sharp, pincer- Epidermis ped maxil-ped

    mandi-let-like lab-maxillary like, articu-only; by lae bles ium laciniae lated cheli-chelicerae cerae C. Blood vessel punc- Stylet-like Stylet-like Slender stylet Blade-like ?None: histo-ture................

    mandibles maxillae formed by maxillary lvtic secre-with finely apposition laciniae tiondis-serrated tips of maxillae - solves tis-sue bits Order of above steps B -+C B -C A ->B-> C A?-B - C B -* A-C? A-B or B-A B. Portable skin microscopes (3, 4) chiefly forstudying the development of the actual bite produced.

    C. Infra-red microscopes (5)-for observing bite reaction and for photomicrography ofstructure.

    2. Skin membrane studies-attempts were made to use human skin as a membrane forstudying the technics of puncture and feeding.

    3. Tracer technics-to attempt to study the progress of the bite after addition of a tracersubstance to the feeding material for mosquitoes and after the direct injection into largerarthropods as the Cimex and the Amblyomma americanum.

    A. Fluorescein B. Isotopes 4. Fixed tissue sections-serial section technics of bitereactions in human and animal skin, early and late reactions in sensitive and non-sensitive skin, biting parts of insects in situ and in some instances the entire insect onthe skin of animals.

    5. Materials applied or injected locally to affect the bite reaction already produced.Insects were obtained from the U. S. Department of Agriculture, Agricultural ResearchAdministration, Bureau of Entomology and Plant Quarantine, Orlando, Florida, throughINSECT BITE REACTION 405 the direction of Dr. W. V. King. The arthropods includedmosquitoes (Aedes aegypti) which were raised in the Department of Dermatology, ticks(Amblyomma americanum) oriental rat fleas (Xenopsylla cheopis) bedbugs (Cimexlectularius) and the chiggers (Eutrombicula alfreddugesii). Several trips were taken to

    Orlando in conjunction with the study for critical review of the findings. Conferenceswere held also at Research Department, Christ >#-* c Fig. 1. Insects on the surface of

    the skin photographed with skin microscopes; Black and white prints from Kodachromes.A. Mosquito-Aedes aegypti-40X; B. Rat flea-Xenopsylla cheopis-40X ; C. Tick-nymph

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    lone star-Amblyomma americanum-40X ; D. Tick- adult female lone star-Amblyommaamericanum-100X; E. Louse-Pediculus humanus corporis on a patch of psoriasis-40X ; F.Chigger-Eutrombicula alfreddugesii-100X.

    Hospital, Cincinnati, with Dr. Leon Schmidt and Dr. Fred Coulston. Anopheles quadri-maculatus used in these investigations were obtained from the Christ Hospital unit. The

    clinical phases were studied in the wards and clinics at the Cincinnati General Hospital,Children's Hospital, and in practice.

    One of the first portions of the study was the attempt to determine whether the insecthas selective localizations for biting on the surface of human skin.

    406 THE JOURNAL OF INVESTIGATIVE DERMATOLOGY Certain factors are important indetermining the site of the insect bite. Some of these factors are temperature, thehumidity of the skin, masses of insects i.e., whether the insects were single or in groups,light, motion, odor and such intrinsic features as the specific attractant features of an

    individual. Previous feeding of the insect is also an important factor in feeding on theskin but not necessarily a consideration for the selection of the area of bite. Our interest

    primarily was an attempt to determine the specific area of the skin preferred by thevarious types of insects. Most of the observations were made with the stereo

    microscope. In the majority of instances the insect would prefer the skin furrow. TheDIAGRAMMATIC REPRESENTATION OF FEEDING PHASES AEDES (Mosquito) CIMEX (BedBug) Skin/ A I /hl 7 f i ' V V Blood V.

    PEDICULUS (Louse) 1 XENOPSYLLA (Flea) i AMBLYOMA (Tick) I EUTROMBICULA(Chigger) Fig. 2. Diagrammatic representation of feeding phases on the skin Aedesoften, however, had no such preferences although the Cimex did. Efforts were made todetermine whether the insect would bite skin lesions. It was found that hungry insects,

    especially mosquitoes, readily bite the heavy patch of psoriasis, the thickened skin ofatopic dermatitis, the oozing ulcers, large sebor-rheic verrucae, and in one patient,

    directly into a hard metastatic adenocarci-noma of the prostate. In this instance the finepenetrating proboscis of the mosquito was inserted directly into this extremely hard

    tumor. Bites of Aedes aegypti were also studied in the two patients with advancedgeneralized scleroderma of the acrosclerotic type. In each patient one bite was done intothe marked atrophic area of one of the fingers (in one patient a trophic lesion waspresent on the tip of this finger) and another simultaneous bite into a relatively softupper area of the upper arm. Early and late skin bite reactions were observed in each ofthese patients. In one patient, the Aedes was required to puncture the atrophic fingerINSECT BITE REACTION 407 area three times to secure an adequate blood meal. Each of

    these areas produced an immediate bite reaction. In this area the pruritus associatedwith the bite was more severe than the pruritus of the bite reaction on the upper arm.The bite reactions were repeated in one of the patients during a prolonged course of

    ACTH which produced some improvement of the scleroderma. Under ACTH therapy, nopruritus or immediate or late reactions were observed.

    On the hairy areas, of course, the Pediculus humanus corporis moved around in anattempt to search for smooth skin. In previous studies Phthirus pubis was : w 7- W-

    ..*>JaHft.

    Fig. 3. Infra-red photomicrographs to show biting parts: A. Mouth parts of tick (Ambly-omma americanum)-75X; B. Mosquito (Aedes aegypti) showing mandible, maxilla andlabium-75X; C. Head of bedbug (Cimex lectularius) with maxillae separated out-75X; D.Dog flea (Ctenocephalides canis) showing maxillary palps; piercing structures partiallyobscured-75 X.

    observed to bite the scalp of children. Attempts to have the Phthirus pubis bite the scalpof adults were unsuccessful. In one experiment, a Pediculus humanus corporis bit the

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    scalp of a young child. Aedes aegypti also bite through the thick skin on the palms of thehand. In observations under the microscope, it was usually not apparent why the insectin response to its reflex responses, probes around before it finds a favorable site. Oftenthe hungry mosquito, especially the Aedes, did not probe but bit immediately. Thereason may be, of course, in the availability of the blood supply in that area rather thanany factors in or on the surface of the skin. In the artificial skin membranes with the

    human skin, the 408 THE JOURNAL OF INVESTIGATIVE DERMATOLOGY few mosquitoesthat did feed, did so after prolonged probing. So, in general with these preliminaryexperiments, there did not seem to be any selective skin site for the hungry insect.Photographs in color at 40 X and 100X of the insect on the surface of the skin were

    taken with the technics reported previously (4). Moving pictures at 20 X and 40 X of theprogress of the insect across the surface of the skin have not been done but are beingplanned.

    The next phase of the problem was the study of the technic of penetration of the skin.This penetration is said to be done either by means of lancet-like sticking, some lancetswith tiny serrations, or by a cutting type of reaction. Muscular action and direct pressureof the body forces the proboscis into and through the skin. Apparently there is a specific

    reflex action setting off this puncture mechanism. An example of the importance of thistechnic of penetration through the skin is cited by Gordon and Crewe (1) with themicrofilariae of onchocerciasis Fig. 4. Chigger (Eutrombicula alfreddugesii): A. Whole

    mount-240X; B. Capitulum showing chelicerae for piercing skin-510 X.

    and of Barter ofti filariasis. The simulium fly, the vector of onchocerciasis as other fliesrasps and cuts the skin and is therefore able to pick up microfilariae in the superficialportion of the papillary area of the dermis where they are found. The mosquito vectors

    of Wuchereria bnerofti penetrate deeply and take up microfilariae directly from thecapillaries where they can obtain more, or from blood pools produced by injury to bloodvessel wall. Therefore, these mosquitoes miss the dermal microfilariae.

    At the suggestion of Lt. Col. Jaswant Singh (6), efforts were made to tamper with andremove portions of the mouth parts of Aedes aegypti. Under ether anesthesia one grouphad the piercing parts separated from the labial sheath, another had the tip of the labialsheath removed, and in some instances the entire lower portion of the proboscis, stillanother group had the mandibles removed. The insects that survived the operativeprocedures were allowed to recover from the anesthesia, usually kept over night. Bitingexperiments were done the next day. After these attempts at feeding, the insects werekilled and mounted to INSECT BITE REACTION 409 study the details of the remaining

    mouth parts. In general, those insects that did survive, probed or rather attempted toprobe. The most active group, of course, was the group with the piercing partscompletely separated from the labial sheath. For successful penetration of the skin, both

    the piercing parts and food channel must be present.

    The obvious difficulty of observation under the microscope was that, for the most part,the view through the microscope was vertically above the biting parts of the insect. Itwas not possible then to see the actual beginning penetration of the skin save in a few

    instances when this was done with Cimex. If the insects were placed on the skin andcovered with small transparent plastic boxes (7) which could be placed in the field of themicroscope, observations on movements over the surface of the skin and into the skincould be done earlier than if the insects were placed on the skin with a test tube.Attempts were made to study the image transmitted through prisms placed adjacent tothe biting areas. These experiments were not successful. Efforts were made to selectareas-whose surface could be shifted in different planes such as forearm, finger, etc. In

    observations on biting on the forearm, it was often not possible to keep the insect inview while it was looking for a biting area with the forearm placed in varying positions.

    By means of the lucite rod attached to microscopic lamps, as we had described inprevious work with cutaneous microscopy (3), efforts were made to try to bring this

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    feeding insects such as the Amblyomma americanum and Cimex use pool feeding. TheEutrombicula is reported after penetration to produce lysis (partial digestion?) of tissueand to aspirate this digested material without any direct or indirect vascular feeding. Asyet, we have not examined any Eutrombicula after feeding, nor do we have, as yet, anyserial section studies on human skin with Eutrombicula. It is believed that at times bitsof chitinous materials of the arthropod may be left in tissue.

    Fluorescein was utilized as a tracer substance for experiments preliminary to the use ofisotopes in insects. Fluorescein was added to the sugar water for Aedes aegypti. Therewas no detection of fluoroscein 3, 6, and 24 hours after feeding. A normal type of whitishfluorescence appears in the white bands of the hind tarsi of Aedes. No fluorescence was

    visible in the bite area of some of these mosquitoes on the skin. Ten Cimex wereinjected with a minute drop of fluorescein. The patterns of injection were studied andappeared concentrated in the local area of injection and were more pronounced in 23

    hours than in 3-4 hours. No fluorescence was visible in the skin area of the bites of 3 ofthese injected 412 THE JOURNAL OF INVESTIGATIVE DERMATOLOGY Cimex. These fewexperiments then demonstrated that it was possible to inject a tracer substance in thelarger insects.

    Radioisotopes have been used in entomology chiefly to study growth and development,action of toxicants, flight patterns, malaria, yellow fever, and plant diseases (15, 16).The isotopes used have been P32, Sr89,1131, Br82. Our preliminary findings are of

    interest and detailed critical studies are under way with Dr. Eugene Saenger (11),Director of the Radioisotope Laboratory at the Cincinnati General Hospital. Iodine131 andP32 were used. For the Aedes aegypti the isotope was put on a cotton sponge moistenedwith 5 percent glucose solution. In a few instances mosquitoes were fed on a patient

    with chronic lymphatic leukemia under P32 therapy. Counts and radioautographs ofwhole insects and portions of insects and skin biopsies are now under study. With thepreliminary experiments Fig, 6. Radioautographs: A. Aedes aegypti after feeding oncotton sponge moistened with I131 added to 5% glucose; entire insect is radioactive

    app. 12X; B. Tick-Amblyomma americanum after injection of I131; festoon pattern inposterior region of abdomen seen app. 12X.

    so far, and using available instrumentation, it has not been possible to use the isotopictechnic to establish definitely the direct entrance into a blood vessel. This, however, wasseen in some instances in the fixed section technic. Greater numbers of more controlledexperiments, and perhaps other isotopes are needed to develop further this isotopictechnic in the study of the insect bite reaction. We utilized the technic of Gordon and

    Crewe (1) of the proboscis in situ in skin to study the question of intravascular feeding.During the actual feeding on the skin, the proboscis was cut, the spot fixed withcollodion, and serial sections done. With the Pediculus humanus corporis and

    Amblyomma americanum an effort was made to cut off a portion of the insect early andlate during the feeding process. Because of the necessity for softening of keratin, thebiopsy material was fixed in Carnoy or Carnoy-Lebrun, afterwards washed with95% alcohol, placed in 4%phenol in 80% alcohol for 24 hours, then through the alcohols

    and cleared in the usual manner. Additional experiments are under way to determineINSECT BITE REACTION 413 the preferred type of fixation technic both for the insect andthe skin. A few experiments were done also with rabbit and guinea pig skin.

    The proboscis in situ also serves as an indicator for studying the intensity of the bitereaction in that particular area of the skin. It is emphasized again that unless one doescareful serial sections a critical evaluation of the intensity of the tissue response to theirritation of the bite cannot be given. It is felt that there is needed a detailed description

    of the histopathology of the early arthropod bite reaction qualified in terms of knownsensitivity of the individual to the bite Fig. 7. Biopsies with proboscis of mosquito

    Anopheles quadrimaculatus in situ H.E. stain: A. Showing fasicle adjacent to blood vessel

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    insect bites on the upper and lower extremities, those in the latter area show greaterpersistency and may even be more severe with vesiculo-bullous reactions and petechiae.In individuals with stasis syndrome of the lower extremities, insect bites may causesevere reactions including extensive ulceration. The reaction of the insect bite to anexternal factor will produce persistent infiltrated nodules in the skin. Such nodules havebeen seen not only after scabies, but also after the bites of other arthropods.

    Independent of external irritant factors, the insect bite reaction may of itself persist forsome time. As Allen (19) and others (20) have indicated, these chronic lesions maysometimes simulate lymphomas. Allen believes that some agent of the arthropod maypersist actively in the tissue for some time. We have observed bits of cuticular material

    in the upper dermis after tick bite.

    Preliminary experiments (17, 18) with the injection of saline, procaine, and cortisone andCompound F into the insect bite reaction by means of the syringe and by the Hypospray

    jet injection apparatus showed, in a few instances, some increased healing withcortisone. This was not marked. Additional experiments are being done utilizing muchsmaller amounts of cortisone. Local Compound F has been found to cause definite

    inhibition of the skin reaction to bites of mosquitoes. The pruritus of chigger bites maybe lessened by direct intra-lesional injection with procaine and Compound F by theHypospray apparatus. More controlled experiments of this type are needed.

    The attempted study of the insect bite mechanism directly and dynamically in the human

    skin illustrates many of the difficulties in such an investigation. This report detailsimportant phases with only preliminary experiments done for many of these phases.Instrumentation with various types of microscopes has its limitations. Attempts in thedirection of skin flap and skin fold and human skin membrane could be continued. The

    study of the infra-red microscope was disappointing especially for direct use on the skin.Animal membranes will have to be tried. Perhaps the detailed and controlled study ofprepared fixed tissue would be of greater value. Because of the delicacy of the biting

    parts and the physical properties of light on and through human skin, it may not bepossible to study the exact progress of this mechanism dynamically in human skin. Theclinical dermatologist must be interested in the mechanism of the insect bite reactionand is urged to contribute his critical findings.

    DISCUSSION Dr. Peck, New York: During the war, the mechanism of insect bites astypified by the louse bite was of practical importance because of the role of lice inspreading typhus fever. My associates and I investigated the louse bite (CutaneousReactions Due to the Body Louse (Pediculus humanus), Peck, S. M., Wright, W. H. and

    Gant, J. Q.; J. A. M. A., 123: 821-825, Nov. 27, 1943). We raised colonies of lice onourselves and in this way were able to observe the process very carefully. The firstevidence of a reaction was always a purpuric spot because of the bite. As allergy

    developed, the typical louse bite reaction was seen which was papular and urticarial. Wewere able to demonstrate that the allergy was due to an antigen in the feces of the louseas well as in the salivary secretions.

    Dr. Beerman, Philadelphia: I am certain that in his rush for time, Dr. Goldman did not

    mean to imply that eight-legged arthropods were insects but, rather 418 THE JOURNALOF INVESTIGATIVE DERMATOLOGY arachnids (mites, etc.). These are to be sure,arthropods, but not of the insect family.

    Dr. Goldman: The pediculi were adapted to feeding on rabbits through the technic ofCulpepper. This is a significant step, by the way, in the study of insect-borne diseases.He has also succeeded in getting small colonies to grow on white rats.

    Now that point brought up about the feces is extremely important in regard to scratchingthe area of an insect bite. For example, South American trypanosomia-sis or Chagas

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    disease is perhaps actually acquired that way, i.e., by rubbing in the bite area theinfected feces of the arthropod. Typhus, as Dr. Peck mentioned, is another example. Wehave seen also eczematization from bites of pediculi.

    Also, we did not mention the technic of studying the bite reaction in situ under themicroscope in determining the vascular patterns, which, incidentally, in cases of

    mosquitoes may sometimes persist for an appreciable length of time.

    The point Dr. Beerman makes is a very excellent one. Many of the insect bite reactionswere done in entomologists. This gave us an unusual opportunity to study bite reactionsin people who knew exactly what species bit them. And they were always very interestedin correcting our terminology. Arthropod is of course the general term which should be

    used.

    Topof pageReferences

    1. Gordon, R. M. and Crewe, W.: The mechanisms by which mosquitoes and tsetseflies obtain their blood meal, the histology of the lesions produced, and thesubsequent reactions of the Kammalian host; together with some observations onthe feedings of chrysops and cimex.Ann. Trop. Med. and Parasitology, 42: 334,December 1948.

    2. Matheson, Robt.: Medical Entomology, 24th Ed., Comstock Publishing Co.,Ithaca,New York, 1950.

    3. Goldman, Leon and Younker, Waldo: Studies in microscopy of the surface of theskin.J. Invest. Dermat., 9: 11, 1947.

    4. Goldman, Leon: Investigative studies with pigmented nevi.J. Invest. Dermat. (inpress).

    5.

    Kline, Jas.: Personal communication to the authors.6. Singh, Lt. Col. Jaswant: Personal communication to the authors.7. Lyons, Wilfred: Personal communication to the authors.8. Bishop, Ann and Gilchrist, Barbara M.: A method for collecting sporozoites of

    plas-modium gallinaceum by feeding of Aedes aegypti through animalmembranes. Nature, 153: 713, 1944. |Article|

    9. Bishop, Ann and Gilchrist, Barbara M.: Experiments upon the feeding of Aedesaegypti through animal membranes with a view to applying this method to thechemotherapy of malaria. Parasitology, 37: 85, January, 1946. |ISI|

    10.Gordon, R. M. and Lummsden, W. H.R.: A study of the behavior of the mouth-parts of mosquitoes when taking up blood from living tissue; together with someobservations on the ingestion of microfilariae.Ann. Trop. Med. andParasitology, 33: 259, 1939.

    11.Saenger, Eugene: Personal communication to the authors.12.Sangiorgi, G. and Frosini, D.: Di un pricipio emolitico ("cimicina") nella saliva

    del "Cimex lectularius". Pathologica 32: (583) 189191, May, 1940.Abstracted by

    Bettini S., Biol. Abstr. 21: 10529, 1947.

    13.Baker, Arthur C.: Personal communication to the authors.14.Griffiths, E. B. and Gordon, R. M.: A simple apparatus designed in order to

    observe insects feeding on living tissue or penetration of helminth larvae.Trans.

    Royal Soc. Trop. Med. and Hyg., 44: 336, Feb., 1951.

    http://www.nature.com/jid/journal/v18/n5/full/jid195248a.html#tophttp://www.nature.com/jid/journal/v18/n5/full/jid195248a.html#tophttp://www.nature.com/doifinder/10.1038/153713a0http://www.nature.com/doifinder/10.1038/153713a0http://www.nature.com/doifinder/10.1038/153713a0http://links.isiglobalnet2.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=Nature&SrcApp=Nature&DestLinkType=FullRecord&KeyUT=A1946YB66000012&DestApp=WOS_CPLhttp://links.isiglobalnet2.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=Nature&SrcApp=Nature&DestLinkType=FullRecord&KeyUT=A1946YB66000012&DestApp=WOS_CPLhttp://links.isiglobalnet2.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=Nature&SrcApp=Nature&DestLinkType=FullRecord&KeyUT=A1946YB66000012&DestApp=WOS_CPLhttp://links.isiglobalnet2.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=Nature&SrcApp=Nature&DestLinkType=FullRecord&KeyUT=A1946YB66000012&DestApp=WOS_CPLhttp://www.nature.com/doifinder/10.1038/153713a0http://www.nature.com/jid/journal/v18/n5/full/jid195248a.html#top
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    15.Jenkins, Dale W. and Hassett, Charles C.Radioisotopes inEntomology,Nucleonics, 6: 5, March, 1950.

    16.Bugher, John C. and Taylor, Marjorie: Radio-phosphorus and radio-strontium inmosquitoes. Science, 110: 146, August 5, 1949.

    17.Preston, Robert H., Goldman, Leon, and Thompson, Lt. Col. Robert G.: The use ofthe Hypospray in dermatology.Arch. Dermat. and Syph. 64: 327(Sept.)1951.

    18.Goldman, Leon, Thompson, Lt. Col. Robert G., and Trice, Capt. Randolph E.:Cortisone acetate in skin disease. Local effect on the skin from topical applicationand local injection.A. M. A. Arch Dermat. and Syph. 65: 177(Feb.) 1952.

    19.Allen, Arthur C.: Persistent "insect bites" (dermal eosinophilic granulomas) simu-lating lymphoblastomas, histiocytosis and squamous cell carcinoma.Amer. J.Path., 24: 367, 1948.

    20.Winer, L. H. and Strakosch, E. A.: Tick bites-Dermacentor Variabilis (Say).J.Invest. Dermat., 4: 249, June, 1941.