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Biomedical subjects

E N Fish

Publications and source records attributed to E N Fish.

49 records · Page 3Linked to original sources
PubMed1986

Antiviral and antitumor effects of a human interferon analog, IFN-alpha Con 1, assessed in hamsters.

An analog of human alpha-and beta-interferons (IFN-alpha and -beta) (generally consisting of the most frequently observed amino acid residue at each position in the molecule) has pronounced antiviral and antiproliferative activity in human and hamster cells. Intraperitoneal administration of this analog (designated IFN-alpha Con 1) to hamsters at 10(6) to 10(8) U/kg resulted in proportional increases in plasma concentrations through 6 h of monitoring. IFN-alpha Con 1 at these doses effectively limited encephalomyocarditis virus (EMCV) infections of hamsters. A natural human IFN-alpha preparation was also active against virus infections in hamsters. The antitumor activity of IFN-alpha Con 1 and natural human IFN-alpha was assessed in hamsters inoculated with lethal TBD932 lymphosarcoma. Various IFN treatment schedules resulted in prolonged survival following tumor challenge. IFN-alpha Con 1 administered at 10(5) to 10(6) U/hamster daily for 9-12 days following tumor challenge was effective in delaying tumor development, as was a natural human IFN-alpha preparation. The efficacies of combined IFN and cyclophosphamide therapies were determined. Unlike the natural human subtype IFN-alpha A, IFN-alpha Con 1 did not diminish the efficacy of cyclophosphamide (2.5 mg/hamster for 3 days) against the lymphosarcoma. However, an ineffective dose of cyclophosphamide (0.05 mg/hamster for 3 days) when combined with IFN-alpha Con 1 treatment showed enhanced antitumor activity. Combinations of cimetidine (16 mg/hamster for 4 days) and IFN-alpha Con 1 treatment did not prolong survival in this model system.

Animals↗
PubMed1986

Antiherpetic effects of a human alpha interferon analog, IFN-alpha Con1, in hamsters.

The efficacy of a novel consensus form of human alpha interferon designated IFN-alpha Con1 was evaluated against herpesvirus infections in vitro and in vivo. At comparable antiviral concentrations, natural lymphoblastoid IFN, IFN-alpha Con1, the molecular subtype IFN-alpha, and the hybrid IFN-alpha AD(Bgl) obtained by recombinant DNA methods conferred similar protection against herpes simplex virus type 1 and type 2 (HSV-2) infections of human cells in vitro. Whereas 7 X 10(5) U of IFN-alpha AD(Bgl) administered in 7 intraperitoneal (i.p.) doses between -4 and 96 h relative to infection protected 90% of mice from a lethal HSV-2 infection, a similar treatment regimen with IFN-alpha Con1 conferred no protection. Systemic HSV-2 infection of hamsters was rapidly lethal, but a single i.p. treatment with 10(6) U of either IFN-alpha Con1 or IFN-alpha AD(Bgl) was highly effective and protected 90 and 75% of animals, respectively, when given 6 h before infection; treatment with IFN-alpha Con1 protected 45% of animals when administered 10 h after infection. In addition, IFN-alpha Con1 was highly protective against acute cervicovaginal HSV-2 infection of hamsters when administered either in a single i.p. dose of 10(6) U at -6 or 10 h relative to infection or in multiple i.p. doses of 10(6) U between -6 and 120 h relative to infection. Protection was manifested by a delay in the onset of and a reduction in duration of infection, a reduction in the number of positive cervicovaginal infections, and an increase in the survival rate.

Animals↗
PubMed1984

Modulation of human interferon-alpha receptor expression by human interferon-gamma.

The human neuroblastoma cell line T98G is sensitive to the antiproliferative activity of both alpha- and gamma-interferons (IFNs). Specific binding of a homogeneous 125I-IFN-alpha 2 probe to high-affinity membrane receptors (apparent Kd = 6.2 X 10(-10) M) can be decreased by pretreatment of these cells with human IFN-gamma (HuIFN-gamma, derived by recombinant DNA techniques). The regulation of HuIFN-alpha 2 binding by such pretreatment is reflected by subsequent inhibition of both the antiviral and antiproliferative activities of HuIFN-alpha 2 on T98G cells. Thus, binding of HuIFN-gamma to its distinct cell-surface receptor can modify expression of the separate IFN-alpha receptor, presumably through an indirect effect on the apparent Kd of the IFN-alpha 2 receptor-ligand interaction.

Burkitt Lymphoma↗
PubMed1983

Human leukocyte interferon subtypes have different antiproliferative and antiviral activities on human cells.

The antigrowth effects of 5 different cloned human leukocyte IFN subtypes (IFN-alpha A, B, C, D, F) and 2 molecular hybrids between them (IFN-alpha AD(Bg1II) and IFN-alpha DA(Bg1II)) were examined on 6 different human cell lines. The results indicate that the interferons sort into two distinct groups: IFN-alpha B, C and F showed comparable antiproliferative activity which was greater than that of IFN-alpha A, D, AD(Bg1II) and DA(Bg1II). The interferons could also be assigned to one of two groups on the basis of their antiviral activity. IFN-alpha A, D and AD(Bg1II) were observed to be more protective than IFN-alpha B, C and F against HSV-2 and EMCV infections, i.e. the relative antiviral efficacies of the cloned IFN subtypes were the reverse of their antiproliferative activities.

Antiviral Agents↗
PubMed1983

Differential binding of human interferon-alpha subtypes to receptors on lymphoblastoid cells.

Highly purified human interferon-alpha subtype A (HuIFN alpha A) was iodinated for use in direct ligand binding studies on human lymphoblastoid (Daudi) cells. Unlabelled preparations of HuIFN alpha subtypes A, C, D, and hybrid molecules AD (Bgl II), AD (Pvu II), and DA (Bgl II) showed different responses in competition experiments with labelled alpha A probe. Specifically, IFNs alpha D and alpha DA were unable to displace the probe, whereas IFNS alpha A, alpha C, and the hybrid alpha ADs showed similar competition curves. These results support a two-idiotope model of IFN recognition by its receptor. IFN effects on [3H]-thymidine incorporation and cell growth (long term effects) did not reflect the apparent affinities of HuIFN alpha subtypes for cell surface receptor.

Binding, Competitive↗
PubMed1983

Antiviral activities of cloned human leukocyte interferons against herpes simplex virus type 2 infections of mice.

Human alpha-interferons (IFN-alpha s) made in bacteria were examined for antiviral activity against herpes simplex virus type 2 (HSV-2) infections of mouse L-cells in vitro, and acute cervicovaginal and lethal systemic HSV-2 infections of BALB/c mice. The recombinant DNA-derived hybrid interferon IFN-alpha AD(Bgl) showed pronounced antiviral activity in vitro, exceeding the activity of either of the parental subtypes IFN-alpha A and IFN-alpha D and that of the other hybrids IFN-alpha AD(Pvu) and IFN-alpha DA(Bgl). A combination of topical and systemic treatments with IFN-alpha A and IFN-alpha AD(Bgl) failed to protect mice from subsequent challenge with an acute cervicovaginal infection of HSV-2. Protection from lethal systemic HSV-2 infection in mice was observed when IFN-alpha AD(Bgl) and IFN-alpha AD(Pvu) were administered systemically, whereas IFN-alpha A failed to confer protection. These results suggest that for protection against infection with HSV-2, the routes of introduction of the virus and of the interferon influence the host response to interferon therapy.

Animals↗
PubMed1979

Organ culture model for the study of HVH-II infections in carcinoma of the cervix.

An experimental model is described whereby human and monkey cervical tissues may be maintained as organ cultures for 21 and 40 days, respectively. Inclusion of sodium carboxymethyl cellulose in the culture medium prolongs the survival time of tissues considerably. The sequential cytologic changes associated with herpesvirus hominis type II (HVH-II) infection are reported. These changes are considered in relation to the possible causal role of HVH-II infection in cervical carcinogenesis.

Animals↗
PubMed1979

Ascending infection following cervicovaginal exposure to herpesvirus hominis type II.

An animal model is presented that demonstrates that following cervicovaginal inoculation, infective doses of herpesvirus hominis type II induce a form of herpetic encephalitis. Immunofluorescent results indicate that there is both neural and hematogenous spread of the herpes infection. The possible role of a latent viral infection in the genesis of an acute disease of the central nervous system is investigated in this experimental system.

Animals↗
PubMed1979

Relation of HVH-II to carcinoma of the cervix.

An animal model is described that demonstrates the development of varying degrees of basal cell hyperplasia, metaplasia, and dysplasia following cervicovaginal herpesvirus hominis type II (HVH-II) infection. Although the study spanned a period of 30 months, the equivalent of 60 human years, there was no evidence of anaplasia. These results are considered in relation to the role of HVH-II as an initiator in the multistep process leading to cervical carcinoma.

Animals↗
PubMed1978

Relation of herpesvirus hominis type II to carcinoma of the cervix. An animal model for the induction of long-term latency of herpesvirus hominis type II.

Proof of latency of herpesvirus hominis type II (HVH-II) following acute vaginocervical infection must be validated if it is to be considered an etiologic factor in carcinoma of the cervix. An animal model is presented which demonstrates acute HVH-II vaginocervical infection. Following the primary acute infection, animals maintained for an equivalent of 60 human years display persistance of the herpesvirus in the pelvic sensory ganglia. Evidence of the specificity of HVH-II as the infectious agent is presented.

Acute Disease↗