Alexander Wildfeuer

Defects in granulocyte function in various chromosome abnormalities (Down's-, Edwards'-, Cri-du-chat syndrome).

ZusammenfassungBei fünf Säuglingen mit Autosomenaberrationen, herabgesetzter Infektresistenz und intaktem humoralen und zellulären Immunapparat wurden die Granulocytenfunktionen Chemotaxis, Phagocytose, intrazelluläre Erregerabtötung und einige Stoffwechselvorgänge experimentell untersucht. Eine serumabhängige bzw. zelluläre Phagocytoseschwäche für Candida albicans bestand bei zwei Säuglingen mit Cri-du-chat-Syndrome und einem anderen mit Trisomie 18. Bei einem dieser Kinder bestand zusätzlich eine serumabhängige, verzögerte Erregerabtötung von Candida albicans sowie von Staphylococcus aureus, wobei die Serumspiegel der Opsonine IgG, IgM, CH 50 und C3 normal waren. Ein Säugling mit Trisomie 21 bot außer einem zellulären Chemotaxisdefekt ein verringertes zelluläres Abtötungsvermögen für Staphylococcus aureus sowie Escherichia coli im Eigen- und im Fremdserum. Die Phagocytose dieser Keime hingegen verlief ungestört.SummaryIn five infants with autosomal aberrations and diminished resistance to infection (in spite of intact humoral and cellular immune mechanisms) several granulocyte functions (chemotaxis, phagocytosis, intracellular killing and metabolism of killing) were measured. A serum-dependent or a cell-dependent disturbance of phagocytosis of Candida albicans was found in two infants with cat-cry syndrome and one with trisomy 18. In one of these children there was an additional serum dependent defect of the killing of Candida albicans and of Staphylococcus aureus, serum levels of opsonins (IgG, IgM, CH50 and C3) being within normal range. An infant with trisomy 21 showed, in addition to a cellular defect of chemotaxis, a reduced cellular ability of the killing of Staphylococcus aureus and of Escherichia coli in autologous and AB-pool-serum. Phagocytosis of these bacteria remained normal.

Impairment of granulocyte function in juvenile diabetes.

ZusammenfassungBei 10 Kindern mit Diabetes wurde die Funktion der Granulocyten getestet. Zum Zeitpunkt der Untersuchung waren die Patienten schlecht eingestellt. Fünf Kinder wurden nach Korrektur der Insulindosis und der Diät eine Woche später erneut getestet. Im Gegensatz zu Berichten aus der Literatur fanden wir keine verringerte Ingestion von Partikeln. Dagegen war die intracelluläre Abtötung von Staphylococcus aureus gestört. Die chemotaktische Aktivität war ebenfalls verringert, während der NBT-Index und die intracelluläre Abtötung von Candida albicans normal waren. Optimale Einstellung des Diabetes führte zu einer Verbesserung der Abtötungsfähigkeit gegenüber Bakterien.SummaryGranulocyte function of 10 diabetic children has been investigated. At the time of testing the diabetes was in poor control. Five children were retested one week later after adjustment of diet and insulin dose. In contrast to some reports we did not find a phagocytic defect in the ingestion of particles, but the capacity of intracellular killing of Staphylococcus aureus was impaired. Chemotaxis was also reduced whereas the NBT-index and intracellular killing of Candida albicans were normal. Better control of the diabetes led to an improvement of bactericidal killing capacity.

Transformation of C18-, C19- and C21-steroids by cultures of Candida albicans.

Abstract Proliferating cultures of Candida albicans were found to contain constitutive 3α-, 3β-, 17β-, 20α- and 20β-hydroxysteroid dehydrogenase activities and to lack steroid hydroxylases and 4-ene-hydrogenases. Ring -A/B-trans configurated steroid (5α-dihydrotestosterone) was the preferred substrate for 3β-reduction. whereas no substrate preference for 3α-reduction was found. The ratio of the two 20-epimeric C21-steroid alcohols formed by 20-reduction was dependent on the substrates structure. Introduction of a 17α-hydroxy group strongly enhanced 20α-reduction whereas an additional 21-hydroxy group decreased 20α-, but increased 20β-reduction. An additional 11-oxo function only weakly decreased both 20β- and 20α-reduction, whereas an 11β-hydroxy group caused a very substantial decrease.

High granulocyte yield with a simple method of filtration leukapheresis

ZusammenfassungEs wurde eine einfache kontinuierliche Filtrationsleukapherese (FL) zur Gewinnung von Granulozyten entwickelt, mit der zwei Leuko-Pak-Filter innerhalb von 5 h mit etwa 12 Liter Blut im geschlossenen System beschickt und eluiert werden können. Der Blutfluß erfolgt dabei ohne Pumpe allein durch Schwerkraft.Die durchschnittliche Ausbeute betrug bei 10 Spendern ohne Vorbehandlung mit Prednisolon 3,66×1010 Granulozyten pro Leukapherese, nach Vorbehandlung mit 150 mg Prednisolon p.o. 6,44×1010 Granulozyten pro Leukapherese. In vitro-Tests zeigten, auch nach Gabe von Prednisolon, keine Einschränkung der Funktionsfähigkeit der Filtergranulozyten.Die vorliegende modifizierte Form der FL hat im Vergleich zur Leukapherese durch Blutzellseparatoren folgende Vorteile:1. Die Granulozytenausbeute bezogen auf Liter separiertes Vollblut ist höher.2. Die Methode kann durch Hilfspersonal in einer Blutbank an mehreren Spendern gleichzeitig durchgeführt werden und sie ist3. wirtschaftlicher als die Leukapherese mit Blutzellseparatoren.SummaryA simple continuous filtration leukapheresis has been devised whereby two Leuko-Pak filters can be charged and eluted within 5 h with approximately 12 l of blood in a closed system of tubes. Blood flows by means of gravity without the use of pumps.Without premedication with prednisolone the average yield from 10 donors was 3.66×1010 granulocytes per leukapheresis and after premedication with 150 mg prednisolone orally it was 6.44×1010 granulocytes per leukapheresis. The in vitro function of filter granulocytes was not reduced even after premedication with prednisolone.In comparison with leukapheresis by blood cell separators this modified method of filtration leukapheresis offers the following advantages:1) the granulocyte yield per litre of whole blood processed is higher,2) technical assistants in a blood-bank can carry out the method on several donors simultaneously,3) the method is more economical than leukapheresis by blood cell separators.

The cervical lymph nodes inStreptococcus pyogenes, group A, type 50, infection in mice

Streptococcus pyogenes, group A, type 50, one of the few group A streptococcal types naturally occuring in mice, proved highly virulent in this species after experimental infection. Intranasal infection of 96 mice (Swiss albino, NMRI, and CBA) with this microorganism induced profound reactions in the cervical lymph nodes of 69% of the animals. Histologically, two different forms of reaction were distinguishable. In 61 mice, the lymph nodes exhibited follicular and lymphoplasmacellular hyperplasia and in 9 animals suppurative lymphadenitis was present. The ability of type 50 streptococci to persist in the pharynx of mice, and the similarity of the morphological changes induced by this organism appear to make intranasal murine group A, type 50, streptococcal infection a suitable model for human streptococcal pharyngitis.

Zur Schockdiagnostik: Der Nachweis von Endotoxin und Mucopeptid mit demLimulus polyphemus-Lysat-Test

SummaryGelation of amebocyte lysate fromLimulus polyphemus (LPL) is induced not only by endotoxins of gramnegative bacteria but also by mucopeptides of various grampositive organisms. Solubilization considerably increases mucopeptide LPL-activity. Total activity of mucopeptide, however, is about 1000-100 000 times smaller than that of endotoxin. In contrast to endotoxin, treatment of mucopeptide with lysozyme causes decrease or complete loss of LPL-activity. Also mucopeptide thus handled does not react any more in the capillary precipitin test. The possibility to destroy mucopeptide LPL-activity by pretreatment with lysozyme permits differentiation from LPL-gelation by endotoxin. In blood specimens of patients with suspected endotoxemia and positive LPL-test mucopeptide induced LPL-reaction therefore can be excluded by pretreatment with lysozyme.ZusammenfassungNicht nur die Endotoxine gramnegativer Bakterien, sondern auch die Mucopeptide verschiedener grampositiver Erreger können eine Gelierung von Amöbocytenlysaten ausLimulus polyphemus (LPL) hervorrufen. Offenbar abhängig von dem Grad der Solubilisierung ist die Wirksamkeit der Mucopeptide zwischen 1000 und 100000mal geringer als die von Endotoxin. Im Gegensatz zu Endotoxin hat die Behandlung von Mucopeptid mit Lysozym eine Abnahme bzw. einen vollständigen Verlust seiner Aktivität im LPL-Test zur Folge. Ein so behandeltes Mucopeptid ist im einfachen Capillarpräcipitationstest unter Verwendung von Antiseren gegen Mucopeptid ebenfalls nicht mehr präcipitierbar. Die Möglichkeit, die LPL-Aktivität von Mucopeptid durch Vorbehandlung mit Lysozym aufzuheben, erlaubt eine Abgrenzung gegenüber der Endotoxin-bedingten LPL-Gelierung. Bei im LPL-Test positiven Blutproben von Patienten mit Verdacht auf Endotoxämie könnte also eine Mucopeptid-induzierte LPL-Reaktion durch Vorbehandlung mit Lysozym ausgeschlossen werden.

Morphological and immunological characteristics ofStreptococcus pyogenes, group A, type 50

Streptococcus pyogenes, group A, type 50, in contrast to other group A streptococci, causes spontaneous disease in mice thereby providing a suitable experimental model for the study of human streptococcosis. Type 50 possesses various peculiar morphological and immunobiological characteristics and under certain conditions forms an extremely thick non-antigenic capsule which seems to interfere with the binding of antibody. This interference is most likely responsible for the difficulties in detecting type 50 streptococci in the tissues of infected mice by immunofluorescent staining. Whereas the surface components (hyaluronic acid, M-antigen) of the type 50Streptococcus exhibit several uncommon features, the more deeply located cell wall antigens, like peptidoglycan and C-carbohydrate, do not differ in either their chemical constituents or their serological reactions from the comparable components of other group A streptococci.

[Granulocyte dysfunction. I. Inborn defects (author's transl)].

The insight in the function and dysfunction of granulocytes lately arouses more and more interest. This report summarises our present knowledge. In the first of two chapters the authors review the molecular basis of granulocyte function and the inborn defects of chemotaxis, opsonisation, phagocytosis and intracellular killing of bacteria and fungi.

Granulocyte dysfunction. Part II. Secondary defects. (authors transl)

In the first part we reviewed both the molecular basis of granulocyte function and the inborn defects. The present chapter summarizes our knowledge of the secondary defects of chemotaxis, opsonisation, phagocytosis and intracellular microbicidal activity.

Critical analysis of granulocyte function in 154 patients with different diseases

SummarySeveral granulocyte functions were analyzed in vitro in 154 patients with chronic or recurrent infections, as well as in a variety of disorders known or suspected to affect host resistance. Only a few specific abnormalities were diagnostic and occurred in congenital, hereditary disorders. Opposed to these permanent changes are those which were probably acquired or transient and are often multifactorial in origin. In the majority of these patients, an inconstant and nonspecific pattern emerged which is not helpful in the diagnosis of underlying disease. In selected patients, however, and as research procedures, these and related tests should be helpful in elucidating the basic functions of granulocytes and may implicate therapeutical approaches.