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Biomedical subjects

E K Thomas

Publications and source records attributed to E K Thomas.

46 records · Page 3Linked to original sources

Human papillomavirus type 16 nucleoprotein E7 is a tumor rejection antigen.

It has been speculated that immunological mechanisms play an important role in the control of carcinomas associated with human papillomavirus (HPV), such as cervical cancers. We have now demonstrated that immunization of C3H/HeN mice by syngeneic nontumorigenic fibroblast-like cells that contain the transfected HPV-16 E7 gene conferred protection against transplanted cells from a HPV-16 E7-positive syngeneic tumor. This protection was HPV-16 E7-specific and was mediated by CD8+ lymphocytes, which presumably were cytotoxic T lymphocytes. These results indicate that tumor cells containing HPV-16 E7, either as a result of transfection, as in our studies, or naturally, as occurs in many human carcinomas, can induce a tumor-specific rejection response and serve as targets for such a response. The system described here provides an animal model to further study immune responses to HPV-associated malignancies and to test the efficacy of anti-HPV vaccines toward the therapy and prevention of such tumors.

Animals↗

Neutralizing monoclonal antibodies to the AIDS virus.

The production of neutralizing monoclonal antibodies (MAbs) will permit the exact localization of neutralizing epitopes on the AIDS virus, HIV-1. We describe the properties of seven MAbs to the envelope of the LAV-1 isolate. Five MAbs recognise the central portion of gp110, amino acids 279-472, and four of these are capable of high-titre neutralization of HIV-1, by infection inhibition, syncytial inhibition and vesicular stomatitis virus (VSV) pseudotype neutralization. One of the two MAbs to gp41 inhibits syncytium formation. Neutralization, live cell immunofluorescence and immunoprecipitation of gp110 are type-specific and restricted to HIV-1 isolates closely related to LAV-1.

Antibodies, Monoclonal↗

Treatment of psychiatric illness by stereotactic cingulotomy.

The treatment of 198 psychiatrically disabled patients with stereotactic cingulotomy was evaluated prospectively for a mean follow-up of 8.6 years. Patients with major affective disorders and anxiety disorders fared the best, with a return to normal functioning in the majority. Patients with obsessive-compulsive disorders, schizophrenia, and personality disorders improved less predictably, with an uneven improvement in functioning that required active ongoing psychiatric treatment. Low mortality and morbidity, a reduction of violent behavior, a possible reduction of suicidal risk, and a lessening of the intractable suffering of chronic psychiatric illness all indicate that cingulotomy can be an effective, safe treatment for patients with affective disorders that are unresponsive to all other forms of therapy.

Adolescent↗

Mutation affecting late gene expression in polyoma virus maps in the late region.

A mutation in polyoma virus strain 3049 which results in the overproduction of capsid proteins has been mapped to the late region of the genome between the HindIII site at 45.0 map units and the BamHI site at 58.6 map units. This region contains the coding sequence for VP3 and a portion of VP2, but does not include the late promoters or the coding sequence for the late leaders. The possible role of VP2 or VP3 in the regulation of genetic expression in polyoma virus is discussed.

Base Sequence↗

Further characterization of Raccoonpox virus.

A poxvirus isolated from the respiratory tract of raccoons in a forest and swamp area near Aberdeen, Maryland, was characterized by biological, serological, and biophysical methods. The virus was shown to be related to the vaccinia-variola subgroup by serological and biophysical methods, but measurably different from the other viruses of this group by biological methods. It causes flaccid paralysis in 1-day-old suckling mice and does not grow well on CAM after two or three passages.

Animals↗

Current concepts in thoracic drainage systems.

Thoracic drainage systems are currently marketed in many varieties, resulting in significant cost and complicating patient management. Realistic needs have been identified from a survey of thoracic surgeons. These are: (1) clear plastic chest catheters with multiple drainage holes in sizes 28, 32, and 36F for adults and 16, 20, and 24F for infants and children; (2) serrated plastic connectors that can be sized at operation; (3) connecting tubes of clear plastic 6 feet long with a diameter of 1/2 inch; (4) a single graduated volume-collecting bottle of 1- to 2-liter capacity that can be emptied and marked, with a separate waterseal component and an associated manometer; and (5) a highflow vacuum source. A drainage system with these characteristics should be safe, effective, simple, and less costly.

Air Pressure↗

Effect of immunization with a vaccinia-HIV env recombinant on HIV infection of chimpanzees.

Acquired immunodeficiency syndrome (AIDS) is caused by human immunodeficiency virus (HIV) and is now recognized as a worldwide epidemic for which there is no cure or vaccine. Chimpanzees are the only other animals that can be infected by HIV, and therefore the chimpanzee-HIV model system is useful for testing potential HIV vaccines. However, with one exception, there have been no reports of clinical manifestations of AIDS in chimpanzees. We report here results of an HIV vaccine trial in which nine chimpanzees were first immunized with either a recombinant vaccinia virus expressing the envelope glycoproteins of HIV strain LAV-1 (v-env5) or a control recombinant vaccinia virus and were then challenged with a high or low dose of LAV-1. Although HIV-specific antibody and T-cell responses were elicited by immunization, virus was isolated from lymphocytes of all challenged chimpanzees, indicating that immunization did not prevent infection by HIV. Among the animals that received a higher dose of LAV-1, one of two control chimpanzees, but none of the four v-env5-immunized chimpanzees developed substantial and persistent lymphadenopathy.

Acquired Immunodeficiency Syndrome↗

Recombinant human CD40 ligand inhibits simian immunodeficiency virus replication: a role for interleukin- 16.

CD40 ligand (CD40L), expressed on activated T cells, binds its receptor, CD40, on dendritic cells, B cells, and monocytes/ macrophages. Human immunodeficiency virus (HIV)-infected individuals exhibit normal B-cell CD40 expression but diminished expression of CD40L on CD4 + T cells. Thus, we studied recombinant human CD40L (huCD40L) in an in vitro rhesus macaque model of acquired immunodeficiency syndrome (AIDS). huCD40L induced peripheral blood mononuclear cell (PBMC) proliferation independent of mitogenic cytokines and led to a 70% reduction in p27 production by simian immunodeficiency virus (SIV) mac239 infected PBMCs (P < 0.05). Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed reduced expression of SIV gag and increased expression of interleukin (IL)-16 mRNA. Supernatants from huCD40L-stimulated PBMC and control cultures contained similar amounts of IL-16, suggesting an intracellular antiviral effect by IL-16. Phytohemagglutinin (PHA)-stimulated PBMCs similarly cultured with huCD40L showed only slight increases in chemokine production (P > 0.05). These results suggest that huCD40L inhibits replication (antigen and mRNA production) of SIVmac239. This response involves huCD40L induction of IL16 mRNA expression and appears to be independent of beta-chemokines.

Animals↗