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Biomedical subjects

N Hardt

Publications and source records attributed to N Hardt.

At least 73 records · Page 4Linked to original sources
PubMed1985

In vivo distribution and activity of aphidicolin on dividing and quiescent cells.

In view of a possible use of aphidicolin, an inhibitor of DNA polymerases (including viral DNA polymerases), to control excessive cell proliferation we have investigated: the effect of the drug on the growth of several human neoplastic cells; the activity of synthetic analogs aimed at relating the structural feature of aphidicolin to cytotoxicity; the in vivo fate and distribution of aphidicolin in different fluids, organs and tissues of mice following parenteral and/or peroral administration.

Animals↗
PubMed1983

Interrelation between viral and cellular DNA synthesis in mouse cells infected with the parvovirus minute virus of mice.

Mouse fibroblasts arrested in G0 by isoleucine deprivation were inoculated with the autonomous parvovirus minute virus of mice (MVM). Infected cells were released from the G0 block by transfer to complete medium and their progression to and and through the S phase was monitored. The onset of viral and cellular DNA synthesis coincided, suggesting that cellular factor(s) required for MVM DNA replication became available as soon as cells entered the S phase. Cellular DNA synthesis was reduced to about 60% by MVM infection. However, this inhibition did not decrease significantly the overall rate of DNA replication in infected cells because it was compensated by concomitant viral DNA synthesis. MVM infection delayed the movement of the cells out of S phase by at least 5 h. At any time post-infection, more than 95% of both viral and cellular DNA synthesis was sensitive to inhibition by aphidicolin. Since this drug is highly specific for cellular DNA polymerase alpha, the data are consistent with a major role of this enzyme in the in vivo DNA replication of autonomous parvovirus. The assembly of 95% of virus progeny particles was concomitant with a late phase or viral DNA replication which accounted for 30% of the total viral DNA synthesized. The inhibition of this residual viral DNA replication by aphidicolin reduced dramatically the size of the burst of infectious particles; this observation concurs with other evidence to suggest that encapsidation is driven by a late replication event sensitive to this drug.

Animals↗
PubMed1983

[Conventional radiology and computed tomography in facial fractures].

The possibilities and limitations of conventional radiography and CT in detecting maxillo-facial fractures are shown both experimentally and in a clinical setting. In 36 patients examined by both methods after maxillo-facial trauma, CT and conventional radiography (including pluridirectional tomography) proved to be equal in detecting fractures of the orbital roof, the anterior wall of the frontal sinus, the nasal bone and the pterygoid process. CT is inferior to conventional radiography in fracture of the orbital floor, the frontal base of the skull, the hard plate and the zygomatic arch. CT is superior to conventional radiography in fractures of the medial and lateral wall of the orbit, the posterior wall of the frontal sinus, the posterior, medial and anterior wall of the maxillary sinus as well as the zygomatic bone.

Facial Bones↗
PubMed1982

Radiation-induced tumor regression as a prognostic factor in patients with invasive cervical cancer.

Radiation-induced tumor regression was evaluated as a prognostic factor in 200 patients with invasive cervical cancer treated at the University of Kentucky Center during the years 1973-1977. Radiation responses were classified as complete (Type A), intermediate (Type B), or incomplete (Type C) based upon pelvic examination findings one month following completion of therapy. Patients with Type A response to radiation had a recurrence rate of 5%, as compared with 27% in patients with a Type B response and 85% in patients with a Type C response. The direct relationship between radiation response and the incidence of tumor recurrence was observed in all stages of disease. Seventy-five percent of patients with Stages IB and IIB disease and a Type C response to radiation developed recurrent cancer, and tumor recurrences were confined to the central pelvis in the majority of cases. Patients with keratinizing squamous cell cancers had the lowest incidence of complete response to radiation. These findings suggest that careful observation of cervical cancer throughout radiation therapy can provide prognostically significant information concerning radiation-induced tumor regression. The therapeutic implications of this data is discussed.

Adenocarcinoma↗
PubMed1981

Aphidicolin does not inhibit DNA repair synthesis in ultraviolet-irradiated HeLa cells. A radioautographic study.

A radioautographic examination of nuclear DNA synthesis in unirradiated and u.v.-irradiated HeLa cells, in the presence and in the absence of aphidicolin, showed that aphidicolin inhibits nuclear DNA replication and has no detectable effect on DNA repair synthesis. Although the results establish that in u.v.-irradiated HeLa cells most of the DNA repair synthesis is not due to DNA polymerase alpha, they do not preclude a significant role for this enzyme in DNA repair processes.

Aphidicolin↗
PubMed1981

An autoradiographic demonstration of nuclear DNA replication by DNA polymerase alpha and of mitochondrial DNA synthesis by DNA polymerase gamma.

The incorporation of thymidine into the DNA of eukaryotic cells is markedly depressed, but not completely inhibited, by aphidicolin, a highly specific inhibitor of DNA polymerase alpha. An electron microscope autoradiographic analysis of the synthesis of nuclear and mitochondrial DNA in vivo in Concanavalin A stimulated rabbit spleen lymphocytes and in Hamster cell cultures, in the absence and in the presence of aphidicolin, revealed that aphidicolin inhibits the nuclear but not the mitochondrial DNA replication. We therefore conclude that DNA polymerase alpha performs the synchronous bidirectional replication of nuclear DNA and that DNA polymerase gamma, the only DNA polymerase present in the mitochondria, performs the "strand displacement" DNA synthesis of these organelles.

Animals↗