PubMed Health⌕ Search

Biomedical subjects

D Dewitt

Publications and source records attributed to D Dewitt.

7 recordsLinked to original sources

Intravenous lipopolysaccharide induces cyclooxygenase 2-like immunoreactivity in rat brain perivascular microglia and meningeal macrophages.

Production of prostaglandins is a critical step in transducing immune stimuli into central nervous system (CNS) responses, but the cellular source of prostaglandins responsible for CNS signalling is unknown. Cyclooxygenase catalyzes the rate-limiting step in the synthesis of prostaglandins and exists in two isoforms. Regulation of the inducible isoform, cyclooxygenase 2, is thought to play a key role in the brain's response to acute inflammatory stimuli. In this paper, we report that intravenous lipopolysaccharide (LPS or endotoxin) induces cyclooxygenase 2-like immunoreactivity in cells closely associated with brain blood vessels and in cells in the meninges. Neuronal staining was not noticeably altered or induced in any brain region by endotoxin challenge. Furthermore, many of the cells also were stained with a perivascular microglial/macrophage-specific antibody, indicating that intravenous LPS induces cyclooxygenase in perivascular microglia along blood vessels and in meningeal macrophages at the edge of the brain. These findings suggest that perivascular microglia and meningeal macrophages throughout the brain may be the cellular source of prostaglandins following systemic immune challenge. We hypothesize that distinct components of the CNS response to immune system activation may be mediated by prostaglandins produced at specific intracranial sites such as the preoptic area (altered sleep and thermoregulation), medulla (adrenal corticosteroid response), and cerebral cortex (headache and encephalopathy).

Animals↗

Osteogenic sarcoma of the jaws: factors influencing prognosis.

Thirty cases of osteosarcoma of the jaws were reviewed (20 men and 10 women, mean age 34 years). Seventeen lesions occurred in the mandible and 13 in the maxilla. Swelling without pain was the most common presenting symptom. Thirteen lesions were initially misdiagnosed as odontogenic infections. Numbness as a presenting symptom was statistically associated with poor prognosis. Treatment included all combinations of surgery, chemotherapy and radiotherapy. Patients receiving chemotherapy with four or more agents showed a trend toward better survival with 71% alive and disease-free at the time of review. Patients' increasing age was statistically associated with decreased survival. The average age of survivors was 27 years and nonsurvivors, 40 years. Older patients suffered more local recurrences which, in all but one case, resulted in mortality. Expectedly, clear surgical margins correlated statistically with improved survival. With margins of less than 5 mm, 27% of patients were alive and disease-free as compared to 62% with surgical margins greater than 5 mm. The importance of early diagnosis, definitive surgical treatment and aggressive adjuvant chemotherapy is demonstrated. The Proportional Hazards Regression model was employed to evaluate the statistical significance of a variety of factors on disease-free and overall survival.

Adolescent↗

Colon rectal cancer: a common disease.

Early diagnosis is a key in properly screening and surveillance. The author discusses preventive medicine, risk ratings, and fecal occult blood testing.

Adult↗

Characterization of inducible cyclooxygenase in rat brain.

Considerable debate exists regarding the cellular source of prostaglandins in the mammalian central nervous system (CNS). At least two forms of prostaglandin endoperoxide synthase, or cyclooxygenase (COX), the principal enzyme in the biosynthesis of these mediators, are known to exist. Both forms have been identified in the CNS, but only the distribution of COX 1 has been mapped in detail. In this study, we used Western blot analysis and immunohistochemistry to describe the biochemical characterization and anatomical distribution of the second, mitogen-inducible form of this enzyme, COX 2 in the rat brain. COX 2-like immunoreactive (COX 2-ir) staining occurred in dendrites and cell bodies of neurons, structures that are typically postsynaptic. It was noted in distinct portions of specific cortical laminae and subcortical nuclei. The distribution in the CNS was quite different from COX 1. COX 2-ir neurons were primarily observed in the cortex and allocortical structures, such as the hippocampal formation and amygdala. Within the amygdala, neurons were primarily observed in the caudal and posterior part of the deep and cortical nuclei. In the diencephalon, COX 2-ir cells were also observed in the paraventricular nucleus of the hypothalamus and in the nuclei of the anteroventral region surrounding the third ventricle, including the vascular organ of the lamina terminalis. COX 2-ir neurons were also observed in the subparafascicular nucleus, the medial zona incerta, and pretectal area. In the brainstem, COX 2-ir neurons were observed in the dorsal raphe nucleus, the nucleus of the brachium of the inferior colliculus, and in the region of the subcoeruleus. The distribution of COX 2-ir neurons in the CNS suggests that COX 2 may be involved in processing and integration of visceral and special sensory input and in elaboration of the autonomic, endocrine, and behavioral responses.

Amygdala↗