Biomedical subjects

K Grünewald

Publications and source records attributed to K Grünewald.

7 recordsLinked to original sources

PubMed1992

A monkey model for Epstein Barr virus-associated lymphomagenesis in human acquired immunodeficiency syndrome.

High-grade malignant nonHodgkin's lymphomas--five lymphoblastic, three pleomorphic, and two immunoblastic--developed in 10/25 cynomolgus monkeys (Macaca fascicularis) followed for up to 746 d after infection with simian immunodeficiency virus, strain SIVsm. These lymphomas were shown to be associated with an Epstein-Barr (EB)-like cynomolgus B-lymphotropic herpesvirus (CBLV) by electron microscopy, by Southern blot hybridization with probes against human EBV, and by the expression of antigens corresponding to EBV-associated nuclear antigens (EBNAs) involved in human B cells transformation. Southern blot demonstration of immunoglobulin gene rearrangements and homogeneous EBV episomes indicated that all the lymphomas were CBLV-associated monoclonal B cell proliferations. Our findings suggest that these tumors correspond to the EBV-associated malignant lymphomas in acquired immunodeficiency syndrome with respect to clinical, morphological, phenotypic, and genotypic characteristics. The particular susceptibility of SIVsm immunodeficient cynomolgus monkeys for CBLV-associated lymphomagenesis appears therefore a useful model for EBV-associated lymphomas in humans.

Animals↗

PubMed1992

[Opportunistic malignant lymphomas in SIV infected primates--a model for Epstein-Barr virus associated lymphomas in AIDS].

In a series of 33 cynomolgus monkeys (Macaca fascicularis) experimentally infected with Simian Immunodeficiency virus (SIV), strain smm3, 13 animals developed malignant Non-Hodgkin lymphomas. These lymphomas presented with unusual primary manifestations like in the orbita, testes, and brain. The morphological features and immunophenotyping identified the tumors as high malignant B-cell lymphomas. In all tumors as well as in tumor-derived cell lines a cynomolgus B-lymphotropic herpes virus (CBLV) with structural homogeneity to the Epstein-Barr virus (EBV) could be demonstrated by Southern blotting with EBV-specific probes. The lymphoma cells also expressed CBLV-associated nuclear antigens involved in B-cell transformation crossreacting with EBNA-specific human sera and monoclonal antibodies. Ig-gene rearrangement studies revealed clonal populations, however, no translocations of the c-myc oncogene could be detected. The lymphomas developing with high frequency in SIV-induced immunodeficiency resemble a major subtype of human EBV-associated AIDS lymphomas. This animal model can therefore be used to further elucidate interactions of HIV and EBV in AIDS-related lymphomagenesis.

Acquired Immunodeficiency Syndrome↗

PubMed1992

P53 mutations in myelodysplastic syndromes.

Point mutations in the p53 tumor-suppressor gene are the most frequently identified genetic alterations in human malignancies. In order to evaluate the role of p53 mutations in the multistep process of leukemogenesis we studied 61 patients with myelodysplastic syndromes using single-strand conformation polymorphism analysis of polymerase chain reaction products as well as direct sequencing. Mutant alleles were observed in 1/14 refractory anemia with excess of blasts (RAEB) and 2/5 RAEB in transformation. The three mutations represented G:C to A:T transitions at codon 141 (exon 5) and codons 245 and 248 (exon 7), respectively. These data suggest that p53 mutations may contribute, albeit rarely, to the development of preleukemic disorders of the myeloid cell lineage.

Anemia, Refractory↗

PubMed1979

[Aplastic anemias].

In the first part of this review diagnostic criteria and prognostic factors are summarized. The results of bone marrow culture with particular reference to the pathophysiology of this disease, are discussed. Finally, the conventional therapeutic approaches are summarized and recent developments in experimental treatment modalities are discussed.

Anemia, Aplastic↗

PubMed1978

[Dacarbacine (DTIC) in the therapy of a malignant disease. A review (author's transl)].

Indications and results are reviewed with regard to recent data on the effect of DTIC in patients with malignant melanoma, soft tissue sarcomas, Hodgkin's disease, gastrointestinal carcinomas and oat cell cancer of the lung. Whilst this drug induced--mainly partial--remissions in 25% of the patients with melanomas, it is generally used in other malignant conditions in combination with other cytoxic agents. In soft tissue sarcomas adriamycin appeared as the principal additional drug. In patients with Hodgkin's disease resistant to MOPP treatment and requiring additional cytotoxic drugs, combination chemotherapy including DTIC may induce remissions in more than half of these patients. Other schedules were, however, also effective and results in this difficult group of patients are discussed and compared. In gastrointestinal and in oat cell carcinomas cytotoxic protocols including DTIC have shown some effect, perhaps comparable to other combinations usually employed in these conditions.

Antineoplastic Agents↗

PubMed1976

[Behavior of vasomotor tonus after lung autotransplantation].

In eight lung autotransplants and six normal lungs the vasomotor activity was tested with norepinephrine and acetylcholine. In autotransplants and normal lungs both substances elicit the same effects. The long-term interruption of the central innervation does not provoke a vasoconstriction in lung autotransplants.

Acetylcholine↗

PubMed1975

[Dopamine effects on the pulmonary circulation of innervated and autotransplanted lungs (author's transl)].

The effects of dopamine on the pulmonary vascular resistance were investigated in 7 normal and 9 autotransplanted canine lungs during perfusion in situ. Dopamine (up to 13,5 gamma/kg BW, rapid injection) acts as a vasoconstrictor by alpha-receptor stimulation. Vasodilative effects could not be registered neither by very small amounts of dopamine nor during alpha-blockade with phentolamine. No difference could be detected between the vascular reactions of normal and autotransplanted lungs.

Animals↗