Deficiency of either cyclooxygenase (COX)-1 or COX-2 alters epidermal differentiation and reduces mouse skin tumorigenesis

Nonsteroidal anti-inflammatory drugs are widely reported to inhibit carcinogenesis in humans and in rodents. These drugs are believed to act by inhibiting one or both of the known isoforms of cyclooxygenase (COX). However, COX-2, and not COX-1, is the isoform most frequently reported to have a key role in tumor development. Here we report that homozygous deficiency of either COX-1 or COX-2 reduces skin tumorigenesis by 75% in a multistage mouse skin model. Reduced tumorigenesis was observed even though the levels of stable 7,12-dimethylbenz(a)anthracene-DNA adducts were increased about 2-fold in the COX-deficient mice compared with wild-type mice. The premature onset of keratinocyte terminal differentiation appeared to be the cellular event leading to the reduced tumorigenesis because keratin 1 and keratin 10, two keratins that indicate the commitment of keratinocytes to differentiate, were expressed 8-13-fold and 10-20-fold more frequently in epidermal basal cells of the COX-1-deficient and COX-2-deficient mice, respectively, than in wild-type mice. Papillomas on the COX-deficient mice also displayed the premature onset of keratinocyte terminal differentiation. However, loricrin, a late marker of epidermal differentiation, was not significantly altered, suggesting that it was the early stages of keratinocyte differentiation that were primarily affected by COX deficiency. Because keratin 5, a keratin associated with basal cells, was detected differently in papillomas of COX-1-deficient as compared with COX-2-deficient mice, it appears that the isoforms do not have identical roles in papilloma development. Interestingly, apoptosis, a cellular process associated with nonsteroidal anti-inflammatory drug-induced inhibition of tumorigenesis, was not significantly altered in the epidermis or in papillomas of the COX-deficient mice. Thus, both COX-1 and COX-2 have roles in keratinocyte differentiation, and we propose that the absence of either isoform causes premature terminal differentiation of initiated keratinocytes and reduced tumor formation.     

Arterial supply to the pig intestine: an unusual pattern in the mesentery

The arrangement of arteries in the mesentery in pigs was studied with latex casts and light microscopy. Arterial arcades, which are characteristic of the mesentery in man and other species, are absent. Instead, a narrow band of numerous, anastomosing arteries gives rise to up to about 500 bundles of arteries and accompanying veins, which radiate out in the mesentery. Each bundle contains up to 30 arteries, but these recombine as they approach the jejunum, and form 1-4 arteriae rectae. The significance of the very large number of small arteries in the mesentery is not known, but they may play a role in the control of blood pressure in the intestinal wall, or as sites of countercurrent exchange.     

Laparoscopic resection of liver metastasis using a harmonic scalpel.

We report successful laparoscopic resection of a solitary liver metastasis from a colorectal carcinoma in an obese man, using a harmonic scalpel.     

Ankle: surface coil MR imaging at 1.5 T

High-field surface coil magnetic resonance (MR) images were obtained of 12 ankles: two from healthy volunteers, seven from patients, and three from fresh cadavers. The cadaver ankles were sectioned in the coronal, sagittal, and axial planes for direct comparison with the MR images. Plain film confirmation of pathologic conditions was obtained in all patients, and five underwent arthroscopy or surgery, or both. MR imaging provided excellent delineation of ligaments and cartilaginous structures in all cases.     

Doctors and the assessment of clinical photographs--does colour blindness matter?

Colour vision deficiency (CVD) is a common anomaly, especially in the male population. A group of doctors with CVD was compared with a control group. Doctors with CVD differed from controls in respect of their ability to detect, and in their confidence in the assessment of, abnormalities presented in clinical photographs. These findings suggest that doctors with CVD should take special care to ensure safe clinical practice.     

Platelet transfusion from donors mismatched for crossreactive HLA antigens

Increments in platelet counts following the transfusion of platelets mismatched for crossreactive antigens were evaluated in 67 patients with broad alloimmunization to HLA antigens. The corrected increments following 100 HLA, A-matched and B1U- or B2U-matched transfusions were compared with the increments following 307 B1X- or B2X-matched transfusions. HLA-A3 platelets were tolerated poorly by A1 and A11 recipients, as were A1 and A11 by A3 recipients, B17 and BW21 by recipients in the B7 crossreactive group, B5 by B15 and B17 recipients, and B27 by recipients in the B5 crossreactive group. B12 and BW21, and B8 and B14 platelets were not tolerated bidirectionally. Antigens associated with good increments included A28 in A2 recipients, B18 and BW16 (C match) in recipients in the B5 crossreactive group, B5 in B18 recipients, BW22 and B7 in recipients in the B7 crossreactive group. A1 and A11 were transfused successfully bidirectionally. These observations suggest that some private antigens within crossreactive groups are more immunogenic than others and support the observation of others than B17 and BW21 are not in the B5 crossreactive group.