In 10 of 14 patients with an active cytomegalovirus (CMV) infection, distinctive large cells (35-45 microns in diameter) were present in the peripheral blood. Morphologically these cells closely resembled the classic cytomegalic inclusion cells, generally regarded as a diagnostic hallmark of CMV infection. Moreover, these cells were shown to express CMV antigens belonging to all three stages of the viral replication cycle, indicating a productive CMV infection. In addition, immunologic staining with monoclonal antibodies directed against cell differentiation and marker proteins showed that these circulating cytomegalic cells were of endothelial origin. The presence of CMV-infected endothelial cells in the peripheral blood of patients with an active CMV infection indicates that such an infection might be accompanied by widespread occult vascular damage.

In a prospective study, 139 serial blood samples from 15 transplant recipients were assessed for the presence of cytomegalovirus (CMV) by virus isolation (CMV viremia) and by direct staining of CMV antigens (CMV Ag) in blood leukocytes (CMV antigenemia). CMV was isolated from 23 samples, whereas CMV Ag was detected in 44 specimens. All positive samples were from a total of nine patients who were diagnosed as having active CMV infections. In seven patients, active CMV infections were diagnosed by virus isolation from blood and urine and by a significant rise of CMV-specific antibodies. In these patients, 21 of the 23 blood samples which were positive for CMV by cell culture were also positive by direct CMV Ag detection. Moreover, CMV Ag were detected in 23 of the 116 culture-negative samples. Twenty of these samples were from the acute phase of infection in the same seven patients. The remaining three CMV Ag-positive specimens were from the other two patients, from whom CMV was not isolated but who had serological evidence of concomitant active CMV infections. These results suggest that direct detection of CMV Ag in peripheral blood leukocytes is as specific as and more sensitive than current isolation techniques. Furthermore, by its sensitivity and inherent rapidity the antigen detection test proved to be the earliest diagnostic marker of active CMV infection in eight of the nine patients. Finally, it was shown that monoclonal antibodies to CMV immediate early antigens are a prerequisite for demonstration of CMV antigenemia.

Human peripheral blood mononuclear cells (PBMCs) were incubated with large unilamellar vesicles (LUV) containing encapsulated dextran-magnetite particles (DMP). This resulted in an efficient incorporation of DMP. Electron microscopy revealed the presence of DMP in cells mainly in phagosomes and secondary lysosomes. DMP-labeled PBMCs showed a strong increase of the transverse relaxation rate (up to 16.6 s-1 for 5 x 10(7) cells/ml) and, accordingly, a great loss of signal intensity in MR imaging. The fraction of DMP containing PBMCs could be enriched by magnetic cell separation. The major population of the DMP containing cells proved to be monocytes. When PBMCs depleted of monocytes were used for labeling, DMP uptake was observed also in the peripheral blood lymphocytes. The labeling of PBMCs presented here may be used in future studies of selective MR imaging of in vivo cell migration in a variety of immunologically compromised tissue states, e.g., tumors, transplantations, and abscesses.

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SummaryMycobacterium ulcerans disease, also known as Buruli ulcer (BU), is a disease of subcutaneous fat tissue. BU is prevalent in riverine and swamp areas of the tropical zone in Africa, Asia and South America, and a few scattered foci in Australia. The mode of transmission of M. ulcerans has not been fully elucidated, but inoculation into the subcutaneous tissues probably occurs through penetrating skin trauma. BU has not been linked with HIV infection. Antimycobacterial drug treatment is ineffective, and treatment is surgical. Patients eventually develop scars and contractures, with resulting disabilities, and the disease imposes a large burden on affected populations. The incidence of BU has dramatically increased in West African countries over the last decade. There is an urgent need for research into host and environmental risk factors for BU in order to develop effective strategies to combat this disease. We review possible genetic host susceptibility factors for BU that are relevant in other mycobacterial diseases: natural resistance-associated macrophage protein-1 (NRAMP-1), HLA-DR, vitamin D 3 receptor, mannose binding protein, interferon-gamma (IFN-c) receptor, tumour necrosis factor alpha (TNF-a), interleukin (IL)-1a, 1b and their receptor antagonists; and IL-12. Schistosoma haematobium infection is highly endemic in many BU foci in West Africa, with a striking increase in transmission after river dams were constructed. This observation, and the observations from interaction of schistosomiasis and tuberculosis, have fuelled our hypothesis that schistosomiasis is a risk factor for BU by driving the host immune response towards a predominantly Th-2 pattern, away from a Th-1 preponderant protection against mycobacterial infection. If the latter hypothesis is con®rmed, enhanced schistosomiasis control should impact on BU.