Biomedical subjects

K M Stanfield

Publications and source records attributed to K M Stanfield.

6 recordsLinked to original sources

PubMed2003

Expression of cyclooxygenase-2 in embryonic and fetal tissues during organogenesis and late pregnancy.

BACKGROUND: Cyclooxygenase (COX) catalyzes the committed step in prostaglandin biosynthesis and exists as two related but unique isoforms, COX-1 (constitutive) and COX-2 (inducible). Prostaglandins (PGs) are known to have many important functions in reproduction, such as placentation and decidualization. Studies with the COX-1 and COX-2 knockout mice have demonstrated that COX-2, but not COX-1, is crucial for normal ovulation, implantation, and decidualization, suggesting that COX-2-derived PGs are important during the initial stages of pregnancy. Although the COX-2 knockout mice did not exhibit any abnormalities at birth, relatively little information exists with regard to the expression of COX-2 in the fetus during development. METHODS: In order to understand the role of COX-2 throughout pregnancy, we characterized the cell type and the temporal expression of inducible COX-2 throughout embryonic and fetal development in the rat (n = 22) by immunohistochemistry and in situ hybridization. RESULTS: High levels of COX-2 expression were seen in decidualized uterine tissue on gestation days 7-13 and then in the fetal membranes on gestation days 17-20. Cyclooxygenase-2 expression was not detectable in any tissues from developing embryos during gestation days 7-13, but was observed in the fetal growth period (gestation days 15-20) in the skin, heart, cartilage, and the kidney. CONCLUSIONS: No COX-2 expression was seen in fetal tissues at days 7-13 of gestation, but was seen in various tissues at days 15-17 of gestation. These observations suggest that COX-2 may be important in mid to late pregnancy through an effect on fetal organ growth, but not in the organogenetic phase of fetal development.

Animals↗

PubMed2001

Localization of cyclooxygenase isozymes in cardiovascular tissues of dogs treated with naproxen.

Prostaglandins have diverse roles in the cardiovascular system mediating both physiologic and inflammatory responses. Two cyclooxygenase isoforms, cyclooxygenase-1 and cyclooxygenase-2, catalyze prostaglandin production. In many tissues and cell types studied, cyclooxygenase-1 is constitutively active whereas cyclooxygenase-2 expression is primarily responsible for prostaglandin production during inflammation. However, little information exists concerning which isoform is responsible for prostaglandin-mediated effects in the heart. We examined cyclooxygenase-1 and cyclooxygenase-2 expression in heart and vascular tissue of dogs using isoform-specific antibodies. In addition, tissues from dogs treated with naproxen (5-10mg/kg/day), an inhibitor of prostaglandin production were also examined. Cyclooxygenase-1 expression was evident in endothelial cells of the microvasculature of the heart, aorta and renal artery. Cyclooxygenase-1 expression was also found in fibrocytes of the tricuspid valve and in the chordae tendinae. Animals treated with naproxen exhibited a similar pattern and intensity of cyclooxygenase-1 staining. No cyclooxygenase-2 expression was evident in cardiac tissue. However, minimal cyclooxygenase-2 immunoreactivity was present in the vascular endothelial cells of small myocardial blood vessels located in several regions of the heart as well as in endothelial cells of the aorta. These data may expand our understanding of the effects of non-steroidal anti-inflammatory drugs on cardiac function.

Animals↗

PubMed2001

Expression of cyclooxygenase-2 in canine renal cell carcinoma.

Cyclooxygenase-2 (COX-2) has been shown to be the primary enzyme responsible for prostaglandin production during inflammation but is absent in most tissues under normal physiological states. High levels of COX-2 expression have been observed in the macula densa and thick ascending limbs of fetal kidneys; this expression declines to minimal levels during renal maturation. We hypothesized that the neoplastic cells of renal cell carcinoma (RCC) may revert to high expression of COX-2, and we evaluated its expression in three spontaneous cases of canine RCC by using immunohistochemical methods. The neoplastic cells of two of the three cases exhibited moderate to marked COX-2 immunoreactivity. These results suggest that some canine renal cell carcinomas express high levels of COX-2, which may play a role in the modulation of neoplastic cell growth.

Animals↗

PubMed1996

Testicular growth and locomotor activity of Siberian hamsters from short-day-responsive and short-day-nonresponsive lineages.

Young of short-day-responsive (SDR/Y) and short-day-nonresponsive (SDNR/Y) Siberian hamsters were reared in a long (16L:8D) photoperiod. At weaning, males from both lineages were maintained in 16L:8D or transferred to a short (12L:12D) photoperiod; body weight and testis size were measured every 7-10 days until 45 or 140 days of age. Contrary to expected results, juvenile SDNR/Ys responded to the inhibitory effects of the shorter photoperiods with decreased body weight and inhibited testicular growth. Under the long photoperiods, SDR/Y and SDNR/Y animals exhibited accelerated body weight gains and testicular growth from 18 to 69 days of age. Beginning at 69 days of age, however, SDNR/Ys exhibited a transient decrease in testis size that troughed at 86 days of age; testis growth subsequently resumed. Consistent with their ability to respond to short photoperiods, SDNR/Y young, in a second experiment, showed locomotor activity patterns similar to those of SDR/Ys in short days (9L:15D). It was only in adult SDNR/Ys that the delayed onset of activity characteristic of nonresponders was apparent. These results indicate that the circadian system of nonresponders changes with age, rendering animals nonresponsive to short photoperiods. The period of transient testicular decline observed in SDNR/Ys housed in 16L:8D may mark a critical period in the onset of these changes; additional studies are required to test this hypothesis.

Animals↗

PubMedDate not supplied

Cyclooxygenase-2 expression in the developing human kidney.

Cyclooxygenase (COX) exists in two related but unique isoforms, COX-1 and COX-2, and is suggested to have specific functions in different segments of the nephron. COX-2 knockout mice develop fatal nephropathy, which implies that this isoform is important during nephrogenesis. The histologic changes seen in the COX-2 knockout mice are similar to those observed in the kidneys of human fetuses exposed to non-steroidal anti-inflammatory drugs (NSAIDs) in the third trimester of pregnancy. However, only minimal amounts of COX-2 mRNA or protein have been reported in the adult human kidney. We hypothesized that expression of COX-2 is significant in the fetal human kidney and that it is involved in the development of the nephron. To characterize the presence of COX-2 in the human fetal kidney, we used immunohistochemistry to evaluate its expression in 23 fetal kidneys ranging between 15 and 23 weeks of gestational age. Strong expression of COX-2 was localized primarily in the macula densa and the thick ascending limb of the loop of Henle, and in rare glomerular podocytes and vascular endothelial cells. There was a progressive decrease in COX-2 immunoreactivity from the most immature nephrons adjacent to the metanephric regions to the well-developed nephrons in the middle to inner cortex. In contrast to the adult human kidney, this temporal and spatial expression of COX-2 in the fetal kidney suggests that this enzyme may be involved in nephrogenesis, and its inhibition by NSAIDs during the third trimester may be responsible for fetal renal syndromes.

Cyclooxygenase 2↗

PubMedDate not supplied

Expression of cyclooxygenase-2 in the macula densa of human kidney in hypertension, congestive heart failure, and diabetic nephropathy.

Cyclooxygenase-2 (COX-2) is constitutively expressed in the macula densa of several laboratory animal species where it is considered to play a physiologic role in the regulation of basal renal function. Pertubations to normal homeostasis is shown to be associated with the upregulation of COX-2 in the macula densa of rats and dogs. In contrast, COX-2 has not been detected in the macula densa of normal adult human and non-human primate kidneys, suggesting a less prominent role of this isoform in normal renal function in these species. In this study, we characterized COX-2 expression in human kidneys collected from subjects with a clinical history indicative of compromised renal function associated with diabetic nephropathy (DN), hypertension, and congestive heart failure (CHF). COX-2 expression was evaluated by immunohistochemistry using isoform-specific antibodies and in situ hybridization. No COX-2 protein or mRNA was observed in the macula densa of normal kidneys (n= 11), whereas slight to moderate COX-2 expression was present in the macula densa of 7/15 subjects (46%) with DN, 5/11 (46%) subjects with hypertension, and 3/10 subjects (30%) with CHF. These results indicate that COX-2 is variably induced in the macula densa of the human kidney in compromised renal conditions and that COX-2-mediated prostaglandins may be involved in maintaining adequate renal functions in some patients with DN, hypertension, and CHF. This variability may be related to individual clinical status or synthesis of vasodilatory prostaglandins by cyclooxygenase-1 (COX-1).

Cyclooxygenase 2↗