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Biomedical subjects

S Broder

Publications and source records attributed to S Broder.

245 records · Page 14Linked to original sources
PubMed1968

Immunologic enhancement of tumor xenografts by pepsin-degraded immunoglobulin.

The serums from guinea pigs previously injected with mouse Ehrlich ascites tumor cells were fractionated to obtain gamma(2)-immunoglobulin. This immunoglobulin was degraded with pepsin to obtain an F(ab')(2) fragment. Fresh tumor cells were incubated with immunoglobulin or the fragment and injected into normal guinea pigs. The growth of these cells as tumor xenografts was inhibited by the gamma(2)-immunoglobulin and enhanced by the F(ab')(2) fragment. Similar incubation of tumor cells with normal guinea pig gamma(2)-globulin or its derived F(ab')(2) fragment did not alter subsequent tumor growth.

Animals↗
PubMedDate not supplied

Interactions between radioresistant T cells from plasmacytoma-bearing mice and radiosensitive T cells from normal mice leading to suppression.

Spleens from BALB/c mice bearing the plasmacytoma SPQC 11 contain a population of T cells capable of suppressing the production of antibodies when cultured with normal BALB/c splenocytes, but not with splenocytes from nude BALB/c mice. Inhibition was characteristically the most effective at low suppressor cell numbers using unirradiated T cells. Maximum suppression occurred when a radiosensitive population of T cells from normal mice interacted with a population of radioresistant T cells from plasmacytoma-bearing animals. Accurate characterization of the suppressor T cell activity required testing over a wide range of suppressor/indicator cell ratios. Suppressor activity was eliminated by treatment with anti-Thy 1.2 plus complement, was radioresistant and present over a full range of doses when irradiated cells were used.

Animals↗
PubMedDate not supplied

Association of human T-cell leukaemia/lymphoma virus with the Tac antigen marker for the human T-cell growth factor receptor.

Certain adult T-cell lymphoproliferative disorders are associated with human T-cell leukaemia virus (HTLV), a unique human type C retrovirus. (The strains of HTLV used in these studies belong to the subgroup HTLV-I.) HTLV is not an endogenous agent in man, but rather is an acquired virus with T-cell tropism. Neoplastic cells from patients infected with HTLV generally express receptors for T-cell growth factor (TCGF) (interleukin-2), and do not require prior activation with antigens or lectins to undergo TCGF-induced proliferation. Furthermore, neoplastic T-cell lines originating from such patients may constitutively produce TCGF, TCGF receptors and HTLV virions. HTLV is transmissible from cell to cell, and the infection of human T cells in vitro is associated with the expression of TCGF receptors, which can be identified by the monoclonal antibody termed anti-Tac. In our experience to date, T-cell populations that produce HTLV without exception also express epitopes found on TCGF receptors. Recognition of an association between HTLV virions and the Tac antigen would have clinical and theoretical implications. We now present evidence that during the replication or release of HTLV, the virion becomes preferentially associated with the Tac antigen.

Antibodies, Monoclonal↗
PubMedDate not supplied

Strategies for antiviral therapy in AIDS.

The retrovirus that causes AIDS has revealed enough of its life history for a variety of therapeutic strategies to be apparent. Some of these are suitable for immediate application in clinical trials or have already yielded positive results in some patients.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Overview of the preclinical development of an antiretroviral drug, 2',3'-dideoxyinosine.

AIDS has remained a significant and worsening medical problem since its first description as a new clinical entity in 1981. In the past 6 years, substantial progress has been made in the chemotherapy for this disease; such progress is likely to exert a major effect on the epidemic of human immunodeficiency virus infection in the coming decade. In this article, we overview the preclinical development of an antiretroviral drug, 2',3'-dideoxyinosine (didanosine; ddI), which has recently been shown in early phase I studies to have activity against human immunodeficiency virus in patients with AIDS or AIDS-related complex. Although we will not know the full clinical potential of ddI until we have the results of ongoing controlled clinical trials, this drug appears to possess desirable features for clinical use.

Animals↗
PubMedDate not supplied

The disposition and metabolism of 2',3'-dideoxycytidine, an in vitro inhibitor of human T-lymphotrophic virus type III infectivity, in mice and monkeys.

The pharmacokinetics and metabolism of the anti-human T-lymphotrophic virus type III/lymphadenopathy-associated virus agent 2',3-dideoxycytidine have been examined in BDF1 mice and rhesus monkeys, with ancillary enzyme studies carried out on tissue derived from both the latter species and also from human subjects. For the pharmacokinetic studies, 2',3-dideoxycytidine and its catabolic product 2',3-dideoxyuridine have been separated and measured in plasma, urine, and cerebrospinal fluid by a reverse HPLC method. For metabolic studies, tritium-labeled drug (labeled in the 5- and 6-positions of the pyrimidine ring) has been employed, utilizing an ion exchange HPLC analytical method suitable for the separation of the parent nucleoside from its mono-, di-, and triphosphates in cell extracts and in tissue homogenates. The drug is rapidly cleared from plasma in a biphasic manner (terminal t 1/2 in BDF1 mice and rhesus monkeys of 67 min and 109 min, respectively) following an iv bolus dose of 325 mg/m2. This two-compartment open model is predictive of plasma concentrations during long term ip infusions in mice. Dideoxycytidine is predominantly excreted in the urine as unchanged parent compound, although a minor urinary metabolite (2,3-dideoxyuridine) is detected in the monkey but not in the mouse. Oral absorption of 2',3'-dideoxycytidine is rapid, with plasma levels approaching those seen after iv administration within 45 min in the mouse. Entry to the central nervous system is also rapid, but the cerebrospinal fluid to plasma AUC ratio after iv administration is only 0.026-0.040 in rhesus monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMedDate not supplied

Progress in drug therapies for HIV infection.

The discovery of effective therapies for HIV requires a fundamental knowledge of retroviral infections. Research by the Public Health Service and collaborating organizations on oncogenic viruses, including retroviruses, has provided much of the basic understanding of retroviruses in general and anti-retroviral therapeutic strategies in particular. Early work by the Viral Cancer and Developmental Therapeutic Programs of the National Cancer Institute and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases has contributed much of the current understanding of AIDS and its therapy. This paper describes the progress that has been made in the treatment of AIDS and the programs that have been created to develop future therapies. These programs include efforts to screen existing compounds for activity against HIV, to design new anti-HIV therapies, and to test potential agents in controlled clinical trials. As a result of these activities, researchers have identified one drug, AZT, that has proven effective in prolonging the lives of some patients with AIDS, and are developing several other promising compounds. The key question no longer is whether HIV infection can be treated, but what is the best and fastest way to develop new therapies and improve existing ones.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Anomalous accumulation and decay of 2',3'-dideoxyadenosine-5'-triphosphate in human T-cell cultures exposed to the anti-HIV drug 2',3'-dideoxyinosine.

The rates of accumulation and decay of 2',3'-dideoxyadenosine-5'-triphosphate (ddATP) have been examined after incubation with the anti-human immunodeficiency virus (HIV) agents 2',3'-dideoxyinosine (ddIno) and 2',3'-dideoxyadenosine (ddAdo) in human T-cell systems frequently used for assay of anti-HIV agents (MOLT-4 and CEM). Formation of ddATP from ddIno or ddAdo was rapid and concentration-dependent, with no saturation of phosphorylation being observed up to extremely high levels (1 mM) of drug. Rates of removal of ddATP from MOLT-4 cells were slow (t1/2 = 25-40 hr) and appeared to be monophasic. These unusually long half-times for ddATP utilization are not a general property of purine dideoxypurine nucleosides: when the corresponding guanine analog (2',3'-dideoxyguanosine) was examined under the same conditions, the t1/2 of ddGTP removal was only 3-5 hr. Similar results were observed with the human T-cell line CCRF-CEM. Coadministration with ddIno of inosine monophosphate dehydrogenase inhibitors, such as ribavirin and tiazofurin, yielded higher levels of ddATP in MOLT-4 and CEM cells, but did not influence the slow removal of ddATP from T-cells. The long half-time for disappearance of ddATP from cells may permit the maintenance of pharmacologically effective levels of ddATP within cells with relatively infrequent administration of the parent drug (ddIno or ddAdo).

Antiviral Agents↗