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Biomedical subjects

D Crase

Publications and source records attributed to D Crase.

At least 19 recordsLinked to original sources

Characterization of the antitumor activities of human tumor necrosis factor-alpha and the comparison with other cytokines: induction of tumor-specific immunity.

We have investigated the in vitro and in vivo antitumor activities of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) against Meth A sarcoma. Meth A sarcoma cells were found to a) be relatively insensitive in vitro to rHuTNF-alpha, and b) express low numbers of TNF-alpha receptors. Intraperitoneally implanted Meth A sarcoma was insensitive to the antitumor effects of rHuTNF-alpha. In contrast, rHuTNF-alpha was highly efficacious against subcutaneously implanted Meth A sarcoma. Biodistribution studies with 125I- or 3H-labeled rHuTNF-alpha demonstrated that, after intravenous administration, the majority of the labeled rHuTNF-alpha localized in the kidney, lungs, and liver. Only low levels of radiolabel were found in subcutaneous Meth A implants. These results support the in vitro data on the low number of TNF-alpha receptors on Meth A sarcoma cells. The ability of rHuTNF-alpha to induce regression of established (7 days) subcutaneous Meth A implants, positively correlated with the degree of both macroscopic and microscopic tumor necrosis. In addition, recombinant human tumor necrosis factor-beta (lymphotoxin) and recombinant murine tumor necrosis factor-alpha induced similar levels of necrosis. Other lymphokines with known antitumor activities, recombinant human interferon-gamma, murine interferon-gamma, and human interleukin 1 alpha, failed to induce detectable necrosis of Meth A sarcoma. Mice which had rejected subcutaneous Meth A sarcoma implants after rHuTNF-alpha treatment and which were later challenged subcutaneously with Meth A sarcoma or other noncross-reacting chemically induced sarcomas were found to be specifically immune to Meth A sarcoma. In addition, low levels of cytotoxic antibodies reactive to Meth A sarcoma were detected in the sera of 21 of 30 Meth A immune mice. Histological evaluation of the hemorrhagic tumor necrosis induced by rHuTNF-alpha suggests that the primary lesion is vascular, possibly directly on the endothelial cells. The mechanisms involved in the generation of specific cell-mediated antitumor immunity in this model are at present unknown.

Animals↗

Development of partial tolerance to the gastrointestinal effects of high doses of recombinant tumor necrosis factor-alpha in rodents.

Treatment of healthy rats and mice with a single intravenous injection of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) caused a dose-dependent gastrointestinal inflammation. Within 30 min gastric emptying was blocked and tissue edema occurred in the small and large intestine. In the cecum hemorrhage occurred after 4 h at doses greater than or equal to 250 micrograms/kg. The cecum exhibited an acute inflammatory response following rHuTNF-alpha treatment similar to that seen in tumor necrosis at the same dose. The vascular endothelium became swollen, increased numbers of neutrophils and other leukocytes attached to and penetrated the endothelium, and finally hemorrhage occurred. Treatment of rats with daily injections of rHuTNF-alpha (250 micrograms/kg per d) for 3 wk failed to produce cachexia. Within 24-48 h rats became resistant to the hemorrhagic effect of rHuTNF-alpha, however, the cytokine still caused a transitory block of gastric emptying after 10 d of treatment. Treatment at 5- or 10-d intervals produced results similar to the initial injection. These results suggest that maximum hemorrhagic response will occur when rHuTNF-alpha is administered at intervals of 5-10 d rather than daily.

Animals↗

Protection from genital herpes simplex virus type 2 infection by vaccination with cloned type 1 glycoprotein D.

Guinea pigs were vaccinated with truncated herpes simplex virus type-1 (HSV-1) glycoprotein D produced in the genetically engineered mammalian cell line gD10.2. Vaccinated animals formed antibodies that neutralized both HSV-1 and herpes simplex virus type 2 (HSV-2) in an in vitro neutralization assay. Vaccinated animals were challenged with HSV-2 by intravaginal infection. Animals that received the immunogen in Freund's complete adjuvant were completely protected from the clinical manifestations of genital HSV-2 infection. Animals that received the immunogen incorporated in alum adjuvants were partly protected from clinical disease; the infections that did develop were significantly less severe than those that occurred in control animals injected with adjuvant alone. The results demonstrate that immunization with a purified viral protein can provide significant protection against primary genital infection by HSV-2 in guinea pigs.

Adjuvants, Immunologic↗

Update: mitral valve prolapse syndrome.

A contemporary "in" diagnosis in the field of cardiology is the mitral valve prolapse syndrome. This abnormality is evident in populations ranging from very young children to older adults. It is being recognized with increasing frequency among college and university students. In many cases, the syndrome is of limited consequence, while in others, it may be life threatening. This paper (1) defines what it is, (2) reports on its occurrence, (3) depicts some relationships with related health entities and (4) discusses certain implications for health professionals and heart health education.

Health Education↗

Death education within health education: current status, future directions.

A national survey was conducted among 205 university level divisions/departments of health education to determine the current status of death education courses within the health education field. Forty-nine college and university health educators currently teaching the course returned usable instruments. Death education receives the same credit, utilizes similar grading systems and is generally managed much like other academic courses. Since the discipline is in its infancy and many teachers are relatively unprepared, respondents called for greater quality control and improved professional preparation. Several concerns accompanying the growth of death education were identified.

Attitude to Death↗