Skin Window Research Articles

Role of blood coagulation in acute inflammation

The inflammatory process is a response to many different kinds of tissue injury. One event thay may be common to many apparently unrelated irritants is the deposition of fibrin. Three experimental designs have considered the significance of fibrin in acute inflammation, but only the third will be discussed extensively (details of the other approaches have been published). In the first approach, the biochemical profile of proteins concerned in fibrin formation was defined quantitatively for inflammatory fluids obtained from acutely inflamed joints of humans with arthritic diseases. Quantitative differences appeared to reflect degress of inflammation rather than to define a profile unique for the types of arthritis. The second experimental approach attempted to correlate the type of exudative leucocytes with the presence of fibrin in human joint disease and experimental skin windows on dogs. The granulocyte phase of inflammation was maintained and prolonged by the presence of fibrin. The third experimental approach was a quantitative study of leucocyte response to the chemotactic power of fibrin, fibrinogen, and their proteolysis products. By a skin window collection chamber technique with dogs, the leucocyte responses to fibrin-related material. other protein aggregates (albumin, γ-globulin, antigen-antibody complexes), and several inert particulate or structured preparations were compared. Fibrin-related materials were the most potent chemotactic agents for granulocyte (predominantly neutrophil) emigration in acute inflammation.

Energization of lymphocytes transforming to macrophages in human inflammation

Transformation of circulating small lymphocytes to macrophages in cell culture and phytohemagglutinin or immunologic stimulation of peripheral blood lymphocyte transformation into large primitive stem cells capable of mitotic division have previously been demonstrated. We have directed our attention to the mode of energization of lymphocytic hypertropy to macrophages in vivo. Appropriately controlled Hotchkiss-Lillie alcoholic-PAS (glycogen) reactivity was followed in the exudative leukocytes responding to an antigenic stimulus in human skin windows. At a critical stage (6–14 hr) of inflammation, in which migration of neutrophils was equalled by migration of lymphocytes, glycogen from neutrophils was shed as cytoplasmic particulates and fragments into the exudative fluids to gain access to the lymphocytes or, more commonly, glycogen transfer was effected by neutrophil-lymphocyte apposition. In such transfers, glycogen first surrounded the lymphocytic cytoplasmic membrane, became incorporated into the membrane, appeared in pinocytotic aggregates just beneath the membrane, and finally underwent dispersion and glycolysis within the cytoplasm. The small number of responding monocytes and histocytes similarly acquired additional glycogen from the neutrophils as they became activated to macrophages. In human skin windows, as in peripheral blood cultures, the infrequent monocytes were identified by direct measurements as well as by structural characteristics. In insulin-deficient patients, neutrophilic cytoplasmic glycogen accumulated in excessive amounts as transfer to lymphocytes failed.

The inflammatory exudate in delayed hypersensitivity

So far, the delayed immune reactions have been the least understood of all antigen-antibody reactions. Recent investigations have shown that they have profound biological functions in conditions in which the defense against macromolecules recognized as foreign is a central factor. The histological changes have been studied, particularly by biopsy, but the cellular exudate has been almost ignored. The exudate in delayed immune reactions had not, before the present investigation, been the subject of systematic studies by the skin window technique. All the experiments were carried out on human subjects. Delayed hypersensitivity reactions were produced experimentally by using heteroantigens (DNCB, tuberculin, and diphtheria toxoid), normal homologous lymphocytes, and autoantigen from thyroid extract in patients with Hashimoto's thyroiditis. The exudate in the delayed cellular processes was found to differ considerably from the nonspecific inflammatory exudate-basophilic and to a lesser extent eosinophilic leukocytes being a new and constant finding, especially during the second day of reaction. They were not observed in concurrent control experiments on the same subject with physiological saline or in nonsensitized subjects. In Walzer's immediate reaction the exudate did not differ in cellular sequence from that in nonspecific reactions. On the basis of these experiments it may be permissible to advance the hypothesis that the basophilic leukocyte acts as a biological amplifier in delayed immune reactions, which are constantly taking place in the organism, in which cellular integrity is to be maintained and foreign antigens appear. The basophilic cells may convert certain stimuli, induced by antigen-antibody reactions, to chemical responses. Persistent liberation of histamine affords the possibility of an afflux of immunologically competent cells. A supply of acid mucopolysaccharides increases the connective tissue content of amorphous compounds and possibly organizes edema fluid into a gel. The aim of the reactions appears to be, in particular, limitation and, if possible, elimination of the foreign antigens from the organism.

Leukokinetic studies. 13. A non-steady-state kinetic evaluation of the mechanism of cortisone-induced granulocytosis.

The mechanism by which adrenocortical steroids induce granulocytosis in man has been investigated using granulocytes labeled with radioactive diisopropylfluorophosphate. After an intravenous injection of 200 mg of cortisol was given to five normal subjects, the mean value for the total blood granulocyte pool increased from 79 to 138 x 10(7) cells per kg of body weight and reflected an increase in the size of both the circulating granulocyte pool and the marginal granulocyte pool. When granulocytes in the circulation were labeled with diisopropylfluorophosphate and granulocytosis was induced later by the intravenous administration of cortisol, the rate of decline of granulocyte specific activity was increased, indicating that the blood pool was being diluted at an accelerated rate by unlabeled cells entering from the bone marrow. The rate of egress of granulocytes from the blood pool to an inflammatory exudate was studied by the "skin window" technique. After the administration of cortisol, there was a mean reduction in the cellularity of induced inflammatory exudates of 75%. However, this reduction in cellularity varied considerably from subject to subject (45-98%). From these studies we can infer that steroids induce an absolute granulocytosis by decreasing the rate of egress of cells from the total blood granulocyte pool as well as by increasing the influx of cells from the bone marrow. By model simulation studies of the non-steady state induced by cortisol injection, it has been possible to quantitate these rate changes. In the present studies cortisol injection resulted in a mean decrease in blood granulocyte egress of 74% (1-99%) and a mean increase in cell inflow of 450% (300-750%).

Leukocytes and hypersensitivity reactions: I. Eosinophil response in skin window to ragweed extract, histamine, and compound 4880 in atopic and nonatopic individuals

Eosinophil counts were made from coverslips obtained from skin windows after intradermal injections of buffered saline, histamine, compound 4880, and mixed ragweed extract in 17 atopic clinically sensitive, 7 skin reacting but clinically nonsensitive, and 11 nonatopic subjects. The concentration of challenging substance was selected on the basis of equal reactivity by titration and wheal size, but other concentrations were also tried. A challenging dose of a size individualized for the subject was necessary to produce the most effective response. When a potent reaginic serum and a proper dose of antigen are used, the eosinophil response in the passively sensitized site is not much different from that in the atopic individual. The response in the atopic, clinically nonsensitive persons appears to be less than the response in those with a history of pollinosis, although the number of subjects and their degree of sensitivity do not permit a final opinion. The eosinophil response to histamine and compound 4880 was found to be greater in atopic clinical than in atopic nonclinical or nonatopic subjects. The eosinophilia from these solutions is usually moderate, is absent at 45 minutes, begins at about 2 hours, is maximal at 6 hours, and is usually negligible at 24 hours. There is considerable variability and inconsistency in the cosinophil determination by this method, some of which is based on factors not yet recognized or corrected. However, it is concluded that conditions which constitute a minimal requirement are: accuracy of dose of challenging substance, a dose selected on basis of titration, repeated trials in the same subject, the counting of at least 1,000 leukocytes, and an averaging of representative areas on the same coverslip.

31 The 'Impotent Neutrophil' Syndrome

Leukocyte function was studied in a 2–2,5-year-old Negro male with the history of repeated abscesses, cervical and inguinal adenitis, recurrent pneumonia, seborrheic eczema of the scalp, hepatosplenomegaly and anemia. An appropriate leukocytosis with neutrophilia occurred with each infection, absolute neutrophil counts ranging from 3,900 to 24,500/mm3. IgG, IgA and IgM globulins were present in increased amounts. Lymph node biopsy contained caseating granuloma. Skin tests and cultures for all types of acid fast bacilli and fungi were repeatedly negative. These findings are characteristic of the syndrome of chronic granulomatous disease of childhood. There was a normal flux of leukocytes into Rebuck skin windows and exudate fluid. Leukocytes appeared normal with alkaline phosphatase, peroxidase and Wright's stain and were normally vacuolated after bacterial phagocytosis. Normal leukocyte motility and phagocytosis followed by degranulation were seen with phase microscopy. Decreased bactericidal activity of the patient's leukocytes during in vitro incubation with Staphylococcus aureus and Aerobacter aerogenes was repeatedly demonstrated in the presence of the patient's serum or normal serum. To determine the nature of this defect a citric acid extract of the patient's leukocyte granules was compared with control specimens and decreased bactericidal activity was found. The deficient or abnormal phagocytin activity of the patient's leukocytes, demonstrated by this study, could account for his clinical syndrome. (SPR)

Local Cellular Faults in Inflammation in the Diabetic—Failure of Glycogen Transport.

s1 May 1967Local Cellular Faults in Inflammation in the Diabetic—Failure of Glycogen Transport.John W. Rebuck, M.D., Ph.D., Fred W. Whitehouse, M.D., F.A.C.P., F. Robert Neher, M.D., Klaus F. Lang, M.D.John W. Rebuck, M.D., Ph.D.Search for more papers by this author, Fred W. Whitehouse, M.D., F.A.C.P.Search for more papers by this author, F. Robert Neher, M.D.Search for more papers by this author, Klaus F. Lang, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-66-5-1060_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe diabetic is allegedly more susceptible to infection than the nondiabetic. We have studied the local cellular reaction to inflammatory stimuli in the diabetic in an attempt to elucidate this problem.Using our skin window technique to study the cellular reaction to stress, we performed 76 test lesions in 37 diabetic patients. Local stimuli included insulin (24 lesions), a suspension of killed Escherichia coli (16 lesions), and diphtheria toxoid (36 lesions). Appropriate control studies have been done. The cellular exudate was stained by the Leishman and periodic acid-Schiff (PAS) techniques.Quantitatively, the cellular response in the diabetic did not differ... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Detroit, Michigan PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1967Volume 66, Issue 5Page: 1060-1061 Issue Published: 1 May 1967 PDF DownloadLoading ...

Drug reactions and the skin window.

Drug reactions and the skin window.

The origin of mononuclear cells in human skin windows.

Acta Pathologica Microbiologica ScandinavicaVolume 68, Issue 3 p. 401-407 Article THE ORIGIN OF MONONUCLEAR CELLS IN HUMAN SKIN WINDOWS HENRIK R. WULFF, HENRIK R. WULFF Med. Dept. B, Copenhagen County Hospital, Hellerup, Denmark (Chief: Povl Riis, M.D).Search for more papers by this authorSTIG SPARREVOHN, STIG SPARREVOHN Med. Dept. B, Copenhagen County Hospital, Hellerup, Denmark (Chief: Povl Riis, M.D).Search for more papers by this author HENRIK R. WULFF, HENRIK R. WULFF Med. Dept. B, Copenhagen County Hospital, Hellerup, Denmark (Chief: Povl Riis, M.D).Search for more papers by this authorSTIG SPARREVOHN, STIG SPARREVOHN Med. Dept. B, Copenhagen County Hospital, Hellerup, Denmark (Chief: Povl Riis, M.D).Search for more papers by this author First published: November 1966 https://doi.org/10.1111/apm.1966.68.3.401Citations: 9AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume68, Issue3November 1966Pages 401-407 RelatedInformation

Skin window: An aid in the diagnosis of drug allergy

The skin-window technique was utilized as a means of diagnosis in 22 instances of suspected drug hypersensitivity in 19 patients. Positive reactions, as noted by eosinophil counts of 18 to 97 per cent, were recorded at test sites in all 5 cases of definite drug hypersensitivity in which reactions had occurred within 8 weeks of testing. Positive reactions, as noted by eosinophil counts of 8 to 90 per cent, were recorded at test sites in 10 to 12 cases with probable drug hypersensitivity in which some of the drug reactions had occurred as long as 20 years previously. There were no systemic reactions following the test and only mild local reactions in 2 cases. Negative tests, as noted by eosinophil counts of 0 to 4 per cent, were noted in distilled water controls and in 4 of 5 cases with equivocal drug hypersensitivity. Tests with other drugs being taken by the patients, to which reactions apparently had not occurred, and tests with drugs in nonallergic individuals also gave responses similar to the distilled water controls.

A Quantitative Rebuck Technic

AbstractA Simple technic is described by which the cells exuded from a skin abrasion can be collected as a cell suspension suitable for quantitation and for further study of the living cells. The technic is identical in principle to the quantitative modification of Rebuck's "skin window" technic which was devised by Perillie and Finch, but the smaller flatter chamber is more easily affixed to the arm and rarely leaks and can be left in place overnight without interfering with sleep. Hence, it is more acceptable to the subjects under study and technically more satisfactory. It provides a method of obtaining normal cells and of studying the cellular reaction to various antigenic or nonantigenic stimuli.

The source of mononuclears at a site inflammation.

1. The intensity of leucocyte emigration to the site of artificially induced inflammation using the modifiedRebuck skin window technique was investigated in patients with different types of hemoblastosis who also had peripheral neutropenia or lymphopenia or monocytopenia. 2. It was found that peripheral neutropenia was regularly followed by decreased emigration to the site of inflammation. 3. On the other hand, peripheral lymphopenia and monocytopenia did not affect the emigration of mononuclears to the site of inflammation. 4. From this it is concluded that in the patients investigated, the mononuclears reached the site of inflammation from the tissue mesenchyme and not from the blood.

The Eosinophil as a Source for Profibrinolysin in Acute Inflammation

Abstract The emigration sequence and cytology of acute inflammation produced by a variety of stimulants was studied in dogs using a modified skin window procedure. Control lesions revealed the typical acute inflammatory cycle with an early influx of polymorphonuclear neutrophils and a later increase in lymphocytes, hypertrophied lymphocytes and macrophages. Either fibrinogen, fibrin or proteolytic enzymes that promote fibrin formation selectively attracted eosinophils into the inflammatory site. Neither histamine nor albumin produced significant eosinophil migration in the 10 hours under study. The fluorescent antibody technic was employed to assess the level of cellular profibrinolysin. Only inflammatory eosinophils and bone marrow eosinophils were marked with rhodamine antiprofibrinolysin. Staining was confined to intra- and extracellular eosinophil granules and coalesced masses. The intensity of fluorescence varied somewhat and perhaps reflected profibrinolysin release into the inflammatory exudate. Exudative eosinophils like all members of the bone marrow eosinophilic series contain profibrinolysin localized in the specific granules. Eosinophils which migrate and collect at an inflammatory site clearly transport profibrinolysin to an area of fibrin deposition. Granule release of profibrinolysin provides one mechanism for fibrinolysis that likely facilitates wound repair.

Interaction of Rickettsiae and Phagocytic Host Cells

Summary In contrast to the focal perivascular collections of mononuclear cells which constitute the classical basic lesion seen in persons dying of typhus fevers, the initial cellular response in man to the presence of typhus rickettsiae, as revealed by the skin window technique, consisted of a typical acute inflammatory reaction. Polymorphonuclear leukocytes appeared within 1.5 hr after introduction of the organisms and increased in numbers during the first 24 hr. Although mononuclear cells began to appear in the lesions between 6 and 12 hr, the polymorphonuclear leukocyte remained the dominant cell throughout the 24-hr observation period. The main difference between the responses of susceptible and immune subjects lay in the more intense polymorphonuclear reaction in the immune subjects. In vivo phagocytosis of living and dead rickettsiae was demonstrable with both polymorphonuclear and larger mononuclear cells in immune as well as nonimmune subjects. The experimental conditions employed reproduced closely the conditions which obtain at the time of natural infection. The implications of these findings with regard to host defense reactions against typhus rickettsiae are discussed.

A study of cellular responses in immune reactions utilizing the skin window technique: I. Immediate hypersensitivity reactions

Tissue eosinophilia has been demonstrated in the skin sites of allergic individuals following application of the allergen. The eosinophilia was greatest with the allergen which clinically seemed to be responsible for the patient's symptoms. Phenergan appeared to increase skin window eosinophilia, although this conclusion must await further study. Application of a topical steroid failed to produce a consistent alteration in eosinophil counts, while oral steroid therapy abolished eosinophilia. The steroid probably exerted its effects by markedly reducing the blood eosinophil level. The suspected chemical mediators of eosinophilia in a skin abrasion were investigated. These studies demonstrated that histamine was capable of inducing tissue eosinophilia in allergic subjects but not in normals, implicating skin-sensitizing antibody as a further prerequisite for the production of tissue eosinophilia.

THE LOCAL CELLULAR RESPONSE IN PATIENTS WITH COCCIDIOIDOMYCOSIS.

The skin window technique was utilized to study the cellular response in patients with various stages of coccidioidomycosis. No significant differences were observed in these patients when compared with a control group suggesting that the cellular response, as measured by this method, is normal in patients with coccidioidomycosis, regardless of the severity and extent of the disease process. The topical application of coccidioidin to the site of abrasion did not alter the response from that obtained with abrasion alone. The presence of a normal cellular response in patients with disseminated coccidioidomycosis and a negative coccidioidin skin test implies that anergy in this instance cannot be attributed to the failure of migration of mononuclear cells to the test site. The histological appearance of the biopsies of the skin tests from a normal control with a negative skin test, from one with a positive test, and from a patient with disseminated coccidioidomycosis and anergy to coccidioidin all appeared similar with mononuclear cell infiltrates of approximately the same extent in the dermis. This discrepancy between the histological features and the clinical appearances of skin test sites provides additional evidence that delayed hypersensitivity of the coccidioidin skin test type is dependent on reactions other than the infiltration of mononuclear cells alone into the area.

Human Skin Window Studies: II. Comparison of Cellular Response to Staphylococcus in Controls and in Patients with Cutaneous Bacterial Infections

experiments with poliomyelitis antigen, reported that subjects with elevated serum neutralizing antibody titer to the antigen had a mononuclear cellular response, in contrast to the absence of such responses in volunteer control subjects who had not been immunized with poliomyelitis vaccine. In 1961, at a meeting of this society, we reported the results of skin window experiments which were designed to study the inflammatory response to the contact allergen, Rhus oleoresin (9). The cellular pattern in subjects with positive patch tests to Rhus was compared with the response in volurteers who had negative patch tests to Rhus. In the subjects with positive patch tests, the response was characterized by a marked increase in eosinophils, large multinucleated giant cells, and an increase in lymphocytes. In our early skin window experiments, it was noted that bacterial contamination of the windows seemed to modify the cellular pattern in a significant manner. Since then, we have emphasized the investigation of the effects of whole cell suspensions of bacteria and bacterial prodncts in the skin windows of individuals with and without cutaneous bacterial infections. The purpose of this report is to describe the cellular patterns which have been observed with suspensions of staphylococci and a purified polysaccharidc antigen prepared from the same strain of staphylococci and finally to discuss the possible significance of these findings.

CYTOGENESIS OF THE EOSINOPHILS OF THE ALLERGIC SKIN EXUDATE (SKIN WINDOW TECHNIQUE).

AllergyVolume 18, Issue 4 p. 317-328 CYTOGENESIS OF THE EOSINOPHILS OF THE ALLERGIC SKIN EXUDATE (SKIN WINDOW TECHNIQUE) A. WEISS, A. WEISS School of Medicine, Cracow, Poland, I. The Allergological Section (Head: Prof. M. Obtutowicz, M.D.) 2. 3-d Clinic of Internal Medicine (Head: Prof. J. Aleksandrowicz, M.D.) 3. Department of Histology (Head: Prof. T. Ackermann, Ph.D.)Search for more papers by this authorT. CICHOCKI, T. CICHOCKI School of Medicine, Cracow, Poland, I. The Allergological Section (Head: Prof. M. Obtutowicz, M.D.) 2. 3-d Clinic of Internal Medicine (Head: Prof. J. Aleksandrowicz, M.D.) 3. Department of Histology (Head: Prof. T. Ackermann, Ph.D.)Search for more papers by this authorJ. BLTCHARSKI, J. BLTCHARSKI School of Medicine, Cracow, Poland, I. The Allergological Section (Head: Prof. M. Obtutowicz, M.D.) 2. 3-d Clinic of Internal Medicine (Head: Prof. J. Aleksandrowicz, M.D.) 3. Department of Histology (Head: Prof. T. Ackermann, Ph.D.)Search for more papers by this author A. WEISS, A. WEISS School of Medicine, Cracow, Poland, I. The Allergological Section (Head: Prof. M. Obtutowicz, M.D.) 2. 3-d Clinic of Internal Medicine (Head: Prof. J. Aleksandrowicz, M.D.) 3. Department of Histology (Head: Prof. T. Ackermann, Ph.D.)Search for more papers by this authorT. CICHOCKI, T. CICHOCKI School of Medicine, Cracow, Poland, I. The Allergological Section (Head: Prof. M. Obtutowicz, M.D.) 2. 3-d Clinic of Internal Medicine (Head: Prof. J. Aleksandrowicz, M.D.) 3. Department of Histology (Head: Prof. T. Ackermann, Ph.D.)Search for more papers by this authorJ. BLTCHARSKI, J. BLTCHARSKI School of Medicine, Cracow, Poland, I. The Allergological Section (Head: Prof. M. Obtutowicz, M.D.) 2. 3-d Clinic of Internal Medicine (Head: Prof. J. Aleksandrowicz, M.D.) 3. Department of Histology (Head: Prof. T. Ackermann, Ph.D.)Search for more papers by this author First published: August 1963 https://doi.org/10.1111/j.1398-9995.1963.tb03186.xCitations: 4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume18, Issue4August 1963Pages 317-328 RelatedInformation

Studies of in Vivo Phagocytosis. I. Inhibition of Phagocytosis by Intact Neoplastic Body Fluids

Abstract 1. By means of a modified skin window technic, the phagocytic response of rabbit leukocytes to external stimuli has been observed. 2. Suspensions of particulate antigens, such as rice starch and Candida albicans, made in serums or urines from patients with leukemias and lymphoproliferative disorders, were not phagocytized normally when compared to similar suspensions in normal media. 3. These results suggest that exogenous or endogenous factors, individually or in combination, interfere with normal phagocytic activity in the rabbit and, by analogy, may exercise a similar function in the human.

Nucleolus studies on the origin of macrophages in skin window preparations

1. Mit der vonRebuck angegebenen Technik gewonnene Hautfensterpraparate wurden der Nucleolenfarbung vonStockinger undKellner unterzogen. 2. Die einkernigen Entzundungszellen der Hautfensterpraparate enthielten in 40,2% einen, in 43,0% zwei, in 14,4% drei, in 2,2% vier und in 0,2% funf Nucleolen. 3. Diese Verteilung wurde zu jedem Zeitpunkt des Entzundungsablaufes (bis 36 Std) unabhangig von der Haufigkeit des Deckglaswechsels gefunden. 4. Die Anordnung der Nucleolarsubstanz in den einkernigen Entzundungszellen zeigte zu keinem Zeitpunkt Ubereinstimmung oder Ahnlichkeit mit den Nucleolen von Blutlymphocyten. 5. Fur eine auf den Deckglaspraparaten zu verfolgende Entwicklung von Makrophagen aus Lymphocyten ergab die Untersuchung keinen Anhalt. 6. Die Befunde sprechen dafur, das die einkernigen Zellen der akuten Entzundung genetisch einheitlich sind.