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Biomedical subjects

N B Finter

Publications and source records attributed to N B Finter.

At least 19 recordsLinked to original sources
PubMed1998

Are all type I human interferons equivalent?

The Type I interferons are a family of closely related cytokines that have antiviral and immunostimulatory properties. There has been prolonged debate regarding the different interferon-alpha subtypes: with some authorities suggest that the different interferons have essentially similar properties but others argue that there are significant differences between them. Recent work has shown that the various interferon-alpha subtypes can interact with the interferon receptor components in different ways and can activate a number of different signalling pathways. Recent studies on the immunomodulatory properties of the Type I interferons indicate that there are profound differences between the subtypes. The clinical significance of all these differences remains to be determined.

Animals↗
PubMed1996

The safety of biopharmaceutical products--a personal viewpoint.

There are now published guidelines dealing with the production of cytokines, monoclonal antibodies and other therapeutic proteins made by applying biotechnological procedures. Strict conformity with these guidelines will undoubtedly yield safe products, but the question can be asked whether all the tests now specified are really essential in relation to the actual risks involved. During many years of experience with some of these biopharmaceutical products, problems which might on theoretical grounds have occurred have in practice not been encountered. Should biopharmaceuticals still be subjected to a much more intense scrutiny than is given to most other medicinal products? Has the time come to review current control procedures? Unnecessary tests increase the cost of products, and may make them too expensive to be available to millions of people who would benefit from their use.

Biological Products↗
PubMed1994

Cytokines in the treatment of virus infections.

The interferon (IFN) system consists of both the formation of the various IFN proteins, and the diverse cellular responses which these induce: these result from the intracellular changes which follow their binding to a specific cell surface receptor. There is only a single human gamma, omega and beta IFN; in contrast, there are 13 closely related chemical species ("subtypes") of human alpha IFN, which are nevertheless chemically and biologically distinct. IFN preparations made from mass cultured human cells or by using recombinant DNA techniques are now readily available for clinical use. IFN have a major role in the defence of the body against virus infections. In acute virus infections, preformed exogenous IFN cannot be given soon enough to be of value. However, IFN-alpha and IFN-beta have proved of considerable value in some chronic virus infections, particularly chronic virus hepatitis and chronic papillomavirus infections. The doses routinely used are associated with both acute and chronic toxic side effects. Also, some patients form specific neutralising antibodies against the particular IFN preparation injected, which may abrogate all the benefits of the treatment. Nevertheless, IFN are now established as agents for use in routine medical practice.

Animals↗
PubMed1991

The use of interferon-alpha in virus infections.

The interferons (IFN) act too slowly to arrest acute viral infections, but interferon-alpha (IFN alpha) preparations have proved useful in some chronic infections and will clearly be used increasingly in these in the future. In the preparations derived from human leucocytes or cultured B lymphoblastoid cells, which are in routine clinical use, mixtures of a number of distinct subtypes of human IFN alpha have been identified. There are also 3 slightly different versions of the same single subtype, IFN alpha-2, made by recombinant DNA procedures in bacteria. IFN alpha preparations are injected intramuscularly or subcutaneously. Dose-related side effects are common but usually tolerable, but prolonged treatment may cause increasing fatigue and depression. Some patients form neutralising antibodies which block the effects of the IFN; these appear to be relatively more common after recombinant IFN alpha-2 than after IFN derived from human cells. Given intranasally, IFN alpha can prevent a subsequent experimental rhinovirus infection, or the spread of natural colds within a family. Repeated administration progressively damages the nasal mucosa, so that long term prophylaxis is not possible. IFN alpha has proved useful in patients with papillomavirus warts of the larynx, ano-genital region (condyloma acuminata) and skin (common warts). Treatment regimens remain to be optimised and are likely to include surgery or other treatments. IFN alpha and zidovudine (azidothymidine) synergistically inhibit the growth of HIV in vitro, and combination are on trial in patients with early AIDS. Very large doses of IFN alpha are effective against Kaposi's sarcoma in some AIDS patients. In chronic hepatitis B, continuing virus replication may lead to cirrhosis or primary liver cancer. Earlier clinical trials with IFN alpha gave inconclusive results, but recent large studies have confirmed that 25 to 40% of patients obtain benefit; this probably results from both the antiviral and the immunomodulatory effects of IFN alpha. In patients with chronic hepatitis C, the biochemical markers usually improve rapidly during IFN alpha administration, but relapse if treatment is stopped after only a few months; to increase the chances of sustained cure, the treatment period is now being prolonged.

HIV Infections↗
PubMed1991

Antibodies in patients with recurrent respiratory papillomatosis treated with lymphoblastoid interferon.

Serum specimens from 53 evaluable patients enrolled in a clinical trial of lymphoblastoid interferon in recurrent respiratory papillomatosis were screened for the presence of interferon-binding antibodies by an indirect enzyme immunoassay and evaluated for neutralizing antibody measured as the inhibition of antiviral activity. Immunoglobulin G antibodies that specifically bound lymphoblastoid interferon were detected in 66% (35 of 53) of patients; neutralizing antibody was detected in 11 of the 35 patients having binding antibody (and in none of the patients who were negative for binding antibody). The incidence of detectable neutralizing antibody in this study population was 20.8% (11 of 53), which is markedly higher than in previous reports of lymphoblastoid interferon in patients with other diseases (i.e., less than 1% incidence). The cumulative dose received at the time of detection of neutralizing antibody ranged from 163 to 385 MU per square meter of body surface. Neutralizing antibody was detectable at a median time of 120 days after initiation of interferon therapy, and binding antibody appeared earlier in those patients (median 59 days) than in patients in whom only binding antibody was produced (median 116 days). Despite the tendency of binding antibody to appear either in patients in whom neutralizing antibody was eventually formed, the detection of binding antibody was not necessarily predictive of the subsequent development of neutralizing antibodies. Binding antibody persisted after neutralizing antibodies had become undetectable.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗
PubMed1989

Detection and incidence of neutralizing antibodies to interferon-alpha-n1.

Sera obtained from 612 patients enrolled in 40 different clinical trials with an interferon-alpha-n1 (IFN-alpha-n1) preparation have been tested for neutralizing activity against this IFN in a cytopathic effect inhibition assay. Positive samples were assayed in triplicate. Of 391 patients treated for human papillomavirus infections, 13 developed neutralizing antibodies (3.3%); two suffering from condylomata acuminata and 11 from juvenile laryngeal papillomatosis (JLP). None has positive titers prior to receiving IFN-alpha-n1 and none appeared to lose the benefits of IFN treatment. Serial specimens from four JLP patients demonstrated that titers rose during IFN treatment and declined postherapy. None of the 221 cancer patients from whom serum samples were available had positive titers. The overall incidence of IFN neutralizing sera from these IFN-alpha-n1 recipients was 2.1%.

Adolescent↗
PubMed1986

The classification and biological functions of the interferons. A review.

There are three main types of interferon, now designated alpha, beta and gamma. Human interferons-alpha exist as many subtypes, probably more than 26. These are chemically quite closely related, but each has a unique chemical composition and biological properties. Preparations of interferon-alpha derived from stimulated peripheral blood leukocytes or lymphoblastoid cell lines contain mixtures of these sub-types; individual sub-types can be obtained by expression of the human gene concerned in bacteria. Human interferon-beta shows about 30% chemical homology with the interferons-alpha. The natural product is glycosylated, and there is only one molecular species. Natural interferon-gamma, also a glycoprotein, has the same non-specific antiviral properties as other types of interferon, but shows little, if any, chemical homology. Recombinant interferons-beta and -gamma have also been prepared by application of gene cloning techniques and expression in E. coli. These proteins are not glycosylated, and differ in their pharmacokinetic behaviour from the natural human proteins. In nature, interferons are normally formed and act locally. If relatively large amounts are administered in order to produce systemic effects, there are dose-related side effects which resemble an attack of influenza.

Animals↗
PubMed1985

Very large scale suspension cultures of mammalian cells.

Suspension cultures of mammalian cells can be used to produce virus vaccines, as a source of interferons, and as a host system for expressing inserted human genes. We will discuss the experience with this technology in our organisation over the past 18 years, during which we have progressively expanded our facilities for such work: we are now operating routinely with 8 000 litre fermenters. Information will be summarized in relation to the following topics: design of plant, medium and serum requirements, plant operation and product processing.

Cells, Cultured↗