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  • 1994  (4)
  • 1
    Language: English
    In: Cell Biology International, April 1994, Vol.18(4), pp.271-278
    Description: The effects of aphidicolin, a specific inhibitor of DNA polymerase alpha, on cell growth, DNA synthesis and myogenic differentiation in the human alveolar rhabdomyosarcoma cell line KFR were studied. The treatment with aphidicolin at 5 x 10(-6) M concentration, which completely inhibited DNA synthesis and cell growth, induced morphological differentiation of small mononuclear cells to elongated, multinucleated (myotube-like) structures. The morphological differentiation was accompanied by the expression of skeletal muscle myosin; about 30% myosin-positive cells were observed after 14 days of treatment, compared to 2.3% in untreated cultures. The results showed that aphidicolin induces differentiation of human rhabdomyosarcoma cells and that multinucleated myotube-like elements may develop simply by cell fusion without cell division and DNA synthesis.
    Keywords: Biology
    ISSN: 1065-6995
    E-ISSN: 1095-8355
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  • 2
    Language: English
    In: Cancer Letters, 1994, Vol.78(1), pp.41-48
    Description: Sodium phenylacetate (NaPA) at concentrations ranging from 2 to 10 mM promoted myogenic differentiation of the human alveolar rhabdomyosarcoma cell line KFR. These concentrations inhibited DNA synthesis of the cells in a dose-dependent manner without significant effect on cell viability. The morphological differentiation of small mononuclear elements to terminal, elongated multinuclear structures resembling myotubes was accompanied by the expression of skeletal muscle myosin. The proportion of differentiated myosin-positive cells which was around 0.8-1.7% in control cultures 12 days after seeding was increased by NaPA treatment up to 47%. In the cytoplasm of differentiated cells, features of sarcomerogenesis were observed. These results suggest that NaPA is an effective inducer of rhabdomyosarcoma cell differentiation at concentrations that have been achieved in humans with no significant adverse effects.
    Keywords: Rhabdomyosarcoma ; Phenylacetate ; Glutamine ; Myogenic Differentiation ; Sarcomerogenesis ; Medicine
    ISSN: 0304-3835
    E-ISSN: 1872-7980
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  • 3
    Language: English
    In: Zentralblatt für Bakteriologie : medical microbiology, virology, parasitology, infectious diseases, 1994, Vol.280(4), pp.540-549
    Description: A seroepidemiological survey for the asssessment of immunity against polioviruses and non-polio enteroviruses (NPEV) seroprevalence was performed using a recently established automated microneutralization assay. The seroprevalences of neutralizing antibodies against Coxsackie viruses B1–B6, and A9, echoviruses 6, 9, 11, and 30, and polioviruses 1, 2, and 3 were investigated in serum samples collected over a period of 30 months (January 1990 to June 1992). Overall, NPEV seroprevalence ranged from 8.3% (Coxsackie virus B6) to 69.8% (echovirus 30). Age-related increases of seroprevalence were only observed for Coxsackie viruses B2 and A9. Relatively low antibody titres were found, the average antibody titre being the highest for Coxsackie virus B2 (1/55.4). The overall poliovirus seropositivity rate reached 80%. The highest seroprevalence was observed in the higher age groups (≥ 50 years). A relatively high proportion (7%) of individuals did not show neutralizing antibodies against all the three poliovirus serotypes. The results of our study have shown that, using an automated microneutralization assay, it is possible to perform seroepidemiological surveys in large patient populations. Until now, no comparable study concerning the NPEV seroprevalence has been performed.
    Keywords: Biology
    ISSN: 0934-8840
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  • 4
    Language: English
    In: Intervirology, 1994, Vol.37(6), pp.307-314
    Description: Effective therapy of human immunodeficiency virus (HIV) infection is mainly based on inhibition of reverse transcriptase by nucleoside analogues such as zidovudine (azidothymidine; AZT), didanosine, and zalcitabine. A major problem associated with long-term AZT therapy is the waning efficacy (‘clinical resistance’) over time. Clinical isolates of HIV-1 with reduced susceptibility to AZT can be recovered from HIV-infected individuals under prolonged treatment. However, the clinical importance of AZT resistance is uncertain. Other factors such as increased virus burden, increased virulence, and AZT toxicity could contribute, singly or in combination, to the loss of therapeutic benefit. Recent observations based on experimental models and clinical trials suggest that cellular mechanisms (‘cellular resistance’) may account for clinical resistance to antiviral agents. In vitro experiments demonstrated that in analogy to antitumoral therapy, the acquisition of multidrug resistance, i.e., resistance of cells to multiple, structurally unrelated chemotherapeutic agents, may play a role in the failure of long-term antiretroviral therapy. The ‘cellular resistance’ may contribute directly to the failure of antiviral therapy by the generation of sub therapeutic levels of antiviral compounds and/or their active forms. Indirectly, such subtherapeutic concentrations of active substances which permit limited replication of virus may represent a selective pressure for emergence and development of a resistant virus population. Hence it is of great importance to investigate the role of cellular factors in ‘clinical resistance’ to AZT and other anti-HIV agents. More detailed knowledge of cellular interactions and antiviral agents could help to improve or develop new strategies for antiviral therapy regimens.
    Keywords: Review Paper ; Cellular Thymidine Kinase ; Viral Resistance Mechanisms ; Reverse Transcriptase ; Multidrug Resistance ; Glycoprotein P ; Biology
    ISSN: 0300-5526
    E-ISSN: 1423-0100
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