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Biomedical subjects

H Mueller

Publications and source records attributed to H Mueller.

94 records · Page 6Linked to original sources

Antibody spectrum against the viral transactivator protein in patients with human immunodeficiency virus type 1 infection and Kaposi's sarcoma.

We analyzed patterns of antibody response to recombinant transactivator protein (human Immunodeficiency virus type 1 [HIV-1] tat) in serum samples from HIV-1-negative subjects (n = 60), HIV-1-infected asymptomatic patients (n = 20), HIV-1-infected patients with Kaposi's sarcoma (n = 25), and patients with Kaposi's sarcoma without HIV-1 infection. None of the healthy subjects possessed anti-tat immunoglobulin G (IgG) in their serum. All asymptomatic patients with HIV-1 infection were anti-tat IgG-positive. Epitope mapping revealed that these sera had anti-tat IgG to all the functional domains of tat protein. Histochemical studies on lymph nodes from five asymptomatic HIV-1-infected patients showed that, in all cases, tat-positive cells were present within the germinal center at the stage of follicular fragmentation containing immunoblasts and small lymphocytes. Of the 25 HIV-1-infected patients with Kaposi's sarcoma, 4 were anti-tat IgG-positive; however, the epitope analysis revealed that IgG to functional domains of tat protein--in particular to transactivating response element (TAR)-binding site--were absent. All patients with Kaposi's sarcoma without HIV-1 infection were anti-tat IgG-negative. Presence or absence of anti-tat IgG and a prevalence of different antibody profiles in different groups of patients indicated the pathophysiologic role of tat protein. Thus, a passive immunization with anti-tat IgG could be a useful strategy to influence the pathophysiologic state of the disease.

Antibodies, Viral↗

The dual role of mutant p53 protein in chemosensitivity of human cancers.

Mutational loss of p53 tumor suppressor functions has been observed in a wide range of neoplasms and was associated with either enhanced or decreased chemosensitivity of affected tumors. The dual role of wild-type p53 as a DNA repair initiator and a trigger for apoptosis raises the possibility that appropriately designed chemotherapy could be selectively applied against p53-defective tumor cells. The cytotoxic effects of DNA-crosslinking chemotherapeutica such as cisplatin could be enhanced by mutated p53 which is no longer able to repair drug-induced DNA damage. In contrast, DNA synthesis blockers such as fluorouracil can induce apoptosis through p53-dependent mechanisms. Thus, loss of p53 functions results in decreased sensitivity to this type of drugs. Clinical studies will reveal the role of abberant p53 in the efficacy of chemotherapy for individual patients.

Apoptosis↗