Gram-negative bacterial pneumonia with secondary aspergillosis in an AIDS patient

Summary A 40-year-old, HIV-infected female patient received antibiotic treatment for a urinary tract infection. After the initial success of therapy and a symptom-free period, she developed pneumonia with septic shock and adult respiratory distress syndrome (ARDS). In spite of intensive care and respirator therapy with positive end-expiratory pressure (PEEP), she died of infectious toxic shock. Autopsy findings showed relapsing, gramnegative, bacterial pneumonia (morphologically compatible with Klebsiella pneumonia) and secondary, invasive aspergillosis. The pathogenesis and epidemiology of these unusual complications of AIDS are discussed.Abbreviations AIDS acquired immunodeficiency syndrome - ARDS adult respiratory distress syndrome - CDC Centers for Disease Control - HIV human immunodeficiency virus - PEEP positive end-expiratory pressure     

A statistically significant sex difference in the number of colony-forming cells from human peripheral blood

 The number of colony-forming cells (CFC) in the peripheral blood (PB) of 43 volunteers was examined using a semisolid clonogenic culture assay. In all, 22 male (age 21–39 years) and 21 female individuals (age 21–39 years) were tested, ten of each group twice to examine the intraindividual variability of colony-forming cells in PB. A statistically significant sex difference in the number of CFC, erythroblastic colonies (BFU-E), and granulocyte/macrophage colonies (CFU-GM) in PB was detected in favor of male individuals. No significant difference between female and male PB was found for the number of CFU-GEMM. The intraindividual variability of CFC and BFU-E was significantly higher in female donors. These results support previous reports by others on a potential influence of sex steroids on hematopoiesis. Received: 8 November 1996 / Accepted: 4 April 1997     

Klinische Charakterisierung der essentiellen Thrombozythämie im Vergleich zu anderen myeloproliferativen Erkrankungen und reaktiven Thrombozytosen

Summary 60 patients with essential thrombocythemia (ET) have been retrospectively and prospectively followed from 1974 through 1987. The presenting signs and symptoms and the course of the disease were analyzed and compared to 10 patients with persisting reactive thrombocytosis selected from 6000 patients with reactive thrombocytosis and to 50 patients with other myeloproliferative diseases. 54 ET-patients presented with complications, 46 with thrombembolic, 3 with hemorrhagic problems and 5 with thrombembolic and hemorrhagic problems. In 6 patients ET was detected accidentally. Disturbances of the microcirculation, mainly of the fingers and the toes, were the most frequent symptom. The average maximal platelet count was 1 207 000/µl. The average platelet count at diagnosis was 880 000/µl. 16 patients had an elevation of the serum creatinin at diagnosis, which deteriorated during the course of the disease. Bone marrow examinations were performed in 56 patients, histology in 48 patients, cytology in 29 patienst. In contrast to the clinical diagnosis the histological diagnosis was in 4 cases each polycythemia vera and myeloproliferative syndrome without further specifiction. 12 patients died thus far. The causes of death were thrombembolic complications in 9, acute leukemia in 2 patients, in 1 patient the cause of death is not known. 10 years after diagnosis 61% of the patients are still alive. It appears that ET is a more important risk factor for the disturbances of the micro- and marcrocirculation than has been recognized until now. ET is, if thrombembolic complications are avoided, a disease with a relatively benign course.

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Abkürzungsverzeichnis ET essentielle Thromobozythämie - PRT persistierende reaktive Thombozytose - PV Polyzythämia vera - CML chronisch myeloische Leukämie - MF Myelofibrose - CMPE chronische myeloproliferative Erkrankung unklarer Zuordnung - MM megakaryozytäre Myelose - ALP alkalische Leukozytenphosphatase - Hb Hämoglobin Herrn Prof. Dr. N. Zöllner zum 65. Geburtstag gewidmet     

Oncogenic retrovirus from spontaneous murine osteomas. II. Molecular cloning and genomic characterization

An N-ecotropic murine leukemia virus (OA MuLV), originally isolated from spontaneous osteomas of strain 101 mice, was molecularly cloned. The virus induces osteomas, osteopetrosis, and malignant lymphomas in NMRI mice. The cloned virus was analyzed by heteroduplex analysis, restriction enzyme mapping, and oligonucleotide mapping. The data show a very close relationship to the endogenous Akv prototype virus with some differences in the gag and the env region. The nucleotide sequence of the U3 region of OA MuLV LTR revealed a structure within the presumable enhancer region very similar to the U3 sequences of the FBJ murine sarcoma virus and its associated helper virus. The significance of these specific structures for the oncogenicity of the virus and the development of the typical disease pattern is discussed.     

Detection and quantification of type C viral proteins in tissues and sera with an enzyme immunoassay.

The in vitro adhesion of three uropathogenic strains of Escherichia coli to epithelial cells from the periurethral area (area surrounding the urethral orifice) of women with and without a history of recurrent urinary tract infections was investigated. All strains showed a specific mannose-resistant hemagglutination restricted to human erythrocytes. Since only a few hundred periurethral cells were used in each test, gentle methods were required. Optimal results were obtained with bacteria grown for 16 h at 37 degrees C in nutrient broth without shaking. The binding of bacteria seemed to be irreversible under the conditions studied, since repeated washings of the epithelial cells after incubation did not decrease the number of adhering bacteria. Chloramphenicol was used to control the number of added bacteria in the incubation system. A difference in the adhesive capacity of periurethral cells of infection-prone and healthy individuals was most evident at concentrations of 2.5 x 10(9) bacteria/ml. Electron microscope studies indicated that pili mediated the adhesion. Adhesion was correlated with the mannose-resistant hemagglutination of human erythrocytes, indicating that the pili were not type 1 pili. Day-to-day variations in the adhesiveness of the bacteria were reduced by selecting well-adhering bacteria with the aid of in vitro passage on periurethral cells or human erythrocytes, and by exclusion of bacteria with low hemagglutination ability.     

Seroepidemiology of HTLV-III (LAV) in the Federal Republic of Germany

Summary In 1984 10,281 sera were collected in the FRG and examined for antibodies to HTLV-III (LAV) with an enzyme-linked immunosorbent assay and confirmative tests. Of the German AIDS patients 81% have antibodies. Individuals belonging to AIDS risk groups, homosexuals, haemophiliacs and i.v. drug abusers, have antibody frequencies between 25%–72%. The detection of HTLV-III antibodies in blood donours indicates that the virus is being transmitted by blood transfusions.Abbreviations AIDS acquired immunodeficiency syndrome - LAS lymphadenopathy syndrome - ARC AIDS related complex - LAV lymphadenopathy associated virus - HTLV-III human T-lymphotropic virus type III - HBV hepatitis B virus     

The use of trimeric isoleucine-zipper fusion proteins to study surface-receptor-ligand interactions in natural killer cells

The ligands for several activating natural killer (NK) cell receptors have not been identified to date. Soluble receptor fusion proteins can be used to stain target cells for the presence of these unidentified ligands. Here, we describe the generation and use of soluble type I NK cell receptor isoleucine-zipper (ILZ) fusion proteins of the immunoglobulin (Ig) superfamily. ILZ-fusion proteins are easy to produce and purify. They form trimeric complexes in solution and display a higher binding avidity than classical immunoglobulin-fusion proteins. ILZ-fusion proteins do not interact with Fc-receptors and can therefore be used to block receptor-ligand interactions in cellular assays. This makes ILZ-fusion proteins a valuable tool to study receptor-ligand interactions in NK cells and other cellular systems.     

Specific detection of Aspergillus species in blood and bronchoalveolar lavage samples of immunocompromised patients by two-step PCR

The increasing incidence of aspergillosis, a life-threatening infection in immunocompromised patients, emphasizes the need to improve the currently limited diagnostic tools. We developed a two-step PCR assay that specifically amplifies a region of the 18S rRNA gene that is highly conserved in Aspergillus species. A number of primers with the least homology to equivalent human or Candida gene sequences were screened for the pairs that gave the highest sensitivity and specificity. No cross-reaction with the wide range of fungal and bacterial pathogens so far tested was observed. This assay allows direct and rapid detection of down to 10 fg of Aspergillus DNA corresponding to 1 to 5 CFU per ml of blood. A total of 315 blood and bronchoalveolar lavage samples from 140 subjects, including 93 patients at risk for invasive fungal disease, were screened. The result was a 100% correlation between positive histology, culture, or high-resolution computed tomography findings and PCR results. The test specificity was 89%. Our data point to the considerable potential clinical value of this simple, specific, rapid, and inexpensive PCR assay for improving the means of early diagnosis of systemic aspergillosis in high-risk patients.     

Treatment intensity significantly influencing fibrosis in bone marrow independently of the cytogenetic response: meta-analysis of the long-term results from two prospective controlled trials on chronic myeloid leukemia.

Bone marrow fibrosis (MF) has been shown to indicate therapy failure in Ph(+) chronic myeloid leukemia (CML). However, the results on the development of MF during interferon-alpha therapy of CML are controversial. The significance of the interferon dose has not been considered as yet. In total, 627 bone marrow biopsies taken prospectively from 200 patients with CML recruited in two studies using different doses of interferon-alpha +/- low-dose cytosine arabinoside were examined for MF before and during therapy. The results showed that the risk of MF depended significantly on the interferon-alpha dose applied (P<0.000005). MF progressed during low-dose therapy (3 x 5 x 10(6) IU/week), but was prevented from progression when applying high dose (5 x 10(6) IU/m(2)/per day). MF disappeared when high-dose interferon-alpha was combined with low-dose cytosine arabinoside (P<0.000005). The risk of death markedly increased when MF occurred or progressed (P<0.0009), independent of all other prognostic factors evaluated including the cytogenetic response. In conclusion, the effectiveness of interferon-alpha on MF depends on the treatment intensity. MF reverses when combining high-dose interferon-alpha with low-dose cytosine arabinoside, but progresses when applying low-dose interferon-alpha. MF appears to be a significant early indicator of ineffective therapy in CML.