Australian-German collaborative studies on the immunology of Sarcocystis infections.

This paper reviews a decade of collaborative studies performed between two laboratories in Germany and Australia on the life cycle, pathogenicity and immunology of infections by the cyst-forming sporozoan parasites Sarcocystis spp. in domestic animals. Experimental transmission studies demonstrated that certain parasite species could cause an acute clinical disease in sheep and pigs severely affecting their health, productivity and reproductivity. Despite the high prevalence of infections found in farm animals, few outbreaks of naturally-occurring clinical disease have ever been recorded. Host animals exposed to low levels of infection were found to develop a strong protective immunity against subsequent lethal challenge and clinical disease even though parasites were not completely eliminated nor prevented from further establishment (premunitive immunity rather than sterile immunity). Modern molecular biological techniques are currently being used to examine the parasite antigens and host immune responses involved in the acquisition of the protective immunity.     

Primary Burkitt Lymphoma of the Chest Wall

IntroductionBurkitt lymphoma (BL) originating in the skin and soft tissue is very rare. To our knowledge, this case of primary sporadic BL presenting as an isolated chest wall mass arising from the soft tissue in an adult may be the first report.Case ReportA previously healthy 33-year-old Caucasian man presented with a 1-month history of a painful lump over the left breast that he initially noticed as a small “pimple-like” lesion in the area. After a week, the skin lesion became larger, erythematous, and painful. At a local hospital, he underwent an incision and drainage procedure for a presumed chest wall abscess. Several days after debridement, a similar lump recurred around the incised area, which rapidly grew in size. He also started experiencing fever and chills for which he was readmitted with a diagnosis of necrotizing chest wall infection. A second debridement with excisional biopsy of the chest wall revealed atypical lymphoid cells, prompting transfer to our institution. Upon transfer, a large, gaping, erythematous and indurated wound with indistinct, thickened borders and extensive edema and necrosis of subcutaneous tissue and musculature of almost the entire left chest wall was noted. No palpable peripheral lymphadenopathy or organomegaly were observed. He underwent minimal debridement and partial excision. The histopathology revealed atypical lymphocytes with prominent nucleoli, deeply basophilic cytoplasm, and abundant lipid vacuoles in a “starry-sky” pattern. The lymphoid population was CD-20 and CD-10 positive, negative for CD-5 and BCL-2, nearly 100% Ki-67 positive, and indeterminate for light chain restriction. Molecular cytogenetic analysis revealed fusion signals with IgH/Myc t(8;14) dual fusion probe, supporting the diagnosis of BL. Staging positron emission tomography (PET)/computed tomography (CT) scan showed a large subcutaneous defect of the left hemithorax involving the dermis, subcutaneous tissue, and musculature, measuring 19.3 × 13.9 × 31.0 cm, with maximal SUV of 9.8 and an average of 6.2. No additional involved sites were seen. The bone marrow biopsy showed minimal involvement by BL and abnormal hybridization pattern for IgH/Myc t(8;14) and Epstein-Barr virus, while the peripheral blood and cerebrospinal fluid showed no involvement. HIV and hepatitis serologies were negative. Three days after surgery, chemotherapy with granulocyte colony-stimulating factor (G-CSF) support was initiated for high-risk disease. He received CODOX-M (intravenous cyclophosphamide, doxorubicin, vincristine, methotrexate; intrathecal cytarabine, methotrexate) as cycle 1 followed by IVAC (intravenous ifosfamide, etoposide, cytarabine; intrathecal methotrexate) with rituximab as cycle 2. He developed tumor lysis without end-organ damage. However, a few days after completion of cycle 2, he developed neutropenic fever and pneumonia, and died in septic shock.DiscussionPrimary chest wall tumors are uncommon. Approximately 50% are malignant, and chest wall lymphoma accounts for < 2%, with extranodal diffuse large B-cell lymphoma being the most common. Primary skin and soft tissue involvement of the chest wall in the absence of detectable lymphadenopathy and visceral disease in an adult by BL has not yet been reported. While there are isolated reports of skin and soft tissue involvement, they were in the setting of immunodeficiency state and were felt to be the result of either iatrogenic tumor seeding after nodal biopsies or local tumor invasion as a manifestation of recurrent disease. This patient's clinical presentation began with the development of an isolated rapidly enlarging chest wall mass that progressed despite surgical debridements.ConclusionThis case illustrates a primary sporadic BL originating in skin and soft tissue in an adult. Whether this case represents a BL that began in the skin and soft tissue and spread to the bone marrow, or began in the bone marrow and spread to the chest wall cannot be determined. The role of tumor debulking procedure is uncertain, although aggressive chemoimmunotherapy with central nervous system (CNS) prophylaxis is warranted as with other BL presentations.     

Transformationsvorgänge in der Frühphase der Entstehung des arteriellen Thrombus

Zusammenfassung In unserer ultrastrukturell durchgeführten Studie wurden Thromben in der Arteria carotis communis von Ratten nach einer zuerst von Meng und Seuter (1977) beschriebenen Methode experimentell erzeugt. Induktion der Thrombusbildung erfolgte in vivo durch Unterkühlung eines kleinen Gefäßabschnittes unter konstantem Druck und kurzfristiger Stase. Eine Änderung des Blutflusses wurde durch einen Silberclip erzeugt. Die geschädigten Gefäßsegmente einschließlich der Thromben bzw. deren Vorstufen wurden nach 5, 10, 30 min und 1, 4 und 24 h nach der Thrombosestimulation entnommen und fixiert. Semidünnschnitte und Ultradünnschnitte wurden im Licht- und Elektronenmikroskop morphologisch untersucht.Den Transformationsvorgängen im Thrombus konnten exakte Zeitmarken zugeordnet werden. Als wichtigstes histopathologisches Merkmal für die Altersbestimmung arterieller Thromben in der Frühphase der Thrombogenese werteten wir die Querstreifung der Fibrinfasern. Diese trat bereits nach 5 min auf, erreichte nach 30 min ein Maximum und verschwand als Folge der zunehmenden Verdichtung der Fasern nach einer Stunde. Nach 4 h sahen wir eine weitgehende Retraktion der Fibrinfasern, die nach 24 h zur Bildung des Fibrinfasergerüstes mit Einmauerung korpuskulärer Elemente führte. Überdies beobachteten wir zwei Thrombocytenaggregate von differenter Struktur. Wir unterschieden ein fibrinarmes Aggregat, in dem die Thrombocyten dichtgepackt und pseudopodienreich erschienen von einem thrombocytenarmen Aggregat mit reichlich interponierten Fibrinfasern. Die nach 5 min im Zentrum des Thrombus auftretende Agglutination der Plättchen im thrombocytenreichen Aggregat führte nach 30 min zur Thrombocytorrhexis und ergab daher einen weiteren Anhalt für die Altersbestimmung des Coagulum. Der entstandene celluläre Abraum stimulierte mononucleäre Zellen und Leukocyten zur Phagocytose. Daher sahen wir nach 4 h eine massive Leukocytose als Folge der frühen Thrombocytorrhexis. Nach 24 h war die viscöse Metamorphose im fibrinreichen und fibrinararmen Aggregat weitgehend abgeschlossen. Innerhalb des beobachteten Zeitraumes entstand eine Verballung und bizarre Deformierung der Erythrocyten, die bereits nach 5 min vom Zentrum des Thrombus ausging und nach 24 h die Peripherie erreichte. Eine Hämolyse der Erythrocyten war nach dieser Zeit noch nicht erkennbar.

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Evolution in the early changes in the establishment of arterial thrombi

Summary Ultrastructural studies of thrombi were carried out on the common carotid artery of the rat using a method first described by Meng and Seuter (1977). Induction of thrombus formation in vivo was achieved by chilling of a small vessel segment under constant pressure and short-termed stasis. Disturbance of the blood flow was produced by a silver clip. The damaged vessel segments with the thrombotic deposits were removed 5, 10, 30 min, and 1, 4 and 24 h after stimulation of thrombosis. They were fixed and samples were studied as semithin and ultrathin sections morphologically using light and electronmicroscopy.In the maturation of thrombi exact time intervals could be determined. The most important histopathological characteristics for age determination of arterial thrombi in the early period of thrombogenesis were the cross stripes of fibrin fibres. They appeared after 5 min, reaching a maximum after 10 min and disappeared as a result of increasing fibre density after 1 h. After 4 h nearly complete retraction of fibrin fibres was found which led after 24 h to the formation of a corresponding frame walling in the corpuscular elements. Apart from this aggregation of thrombocytes, which were of two different types were observed, one showing a fibrin-poor aggregate in which the thrombocytes appeared densely packed with numerous pseudopods, and one showing a thrombocyte poor aggregate with abundant interposed fibrin fibres. Agglutination of platelets which occurred in the thrombocyte-rich aggregate in the centre of the thrombus after 5 min led to thrombocytorrhexis after 30 min. The resulting cellular waste stimulated phagocytosis by mononuclear cells and leucocytes. Because of this a massive leucocytosis was found as a result of the early thrombocytorrhexis after 4 h. After 24 h the viscous metamorphosis in the fibrin-rich and in the fibrin-poor aggregate was largely completed. Clumping and deformation of erythrocytes was observed in the middle of the thrombus after 5 min and at the periphery of the thrombus after 24 h. Haemolysis did not occur within this time interval.

Frau Antoni, Herrn Ing. grad. Derks und Herrn Rieger sei für ausgezeichnete technische Assistenz herzlichst gedankt.     

Development of a syncytia inhibition assay for the detection of antibodies to bovine leukemia virus in naturally infected cattle; comparison with Western blot and agar gel immunodiffusion

A syncytia inhibition assay (SIA) for the detection of antibodies to bovine leukemia virus is described. This test involves specific antibody-mediated inhibition of BLV-induced cytopathic effects in an indicator cell line. A total of 300 sera were screened commercially by agar gel immunodiffusion (AGID) and were then screened by Western blot and SIA. The new assay system provided results which were comparable to Western blot and AGID. The results obtained suggest that SIA may be more sensitive than either of the other two assay systems examined for the determination of the infection status of cattle.     

Leiomyoma cells with 12q15 aberrations can be transformed in vitro and show a relatively stable karyotype during precrisis period

Tumor cells from three uterine leiomyomas showing translocations involving 12q14-15 were transformed by transfection using the "early regions" of the SV40 genome. The cells had a higher proliferative capacity, were able to form colonies in soft agar, and showed an increased growth potential. Karyotype analyses of these transformed leiomyoma cells showed that the cells had retained the initial t(12;14) and t(12;15).