The expression of the KAI1 gene, a tumor metastasis suppressor, is directly activated by p53.

KAI1 is a tumor metastasis suppressor gene that is capable of inhibiting the metastatic process in animals. The expression of the KAI1 gene also is found to be down-regulated during the tumor progression of prostate, breast, lung, bladder, and pancreatic cancers in humans, and this down-regulation appears to be at or posttranscription level. We have found that the tumor suppressor gene p53 can directly activate the KAI1 gene by interacting with the 5' upstream region. The p53 responding region is located at approximately 860 bases upstream of the transcriptional initiation site, and it contains a typical tandem repeat of the p53 consensus-binding sequence. A gel-shift mobility analysis showed that this sequence indeed had the ability to bind to the purified p53 protein. Mutations of this sequence abolished the responsiveness to p53 and also the binding ability to the p53 protein. Furthermore, immunohistochemical analysis of 177 samples of human prostate tumors revealed that the expression of the KAI1 gene was correlated strongly to that of the p53 gene and that the loss of these two markers resulted in poor survivals of patients. Our data indicate a direct relationship between p53 and KAI1 genes and suggest that the loss of p53 function, which is commonly observed in many types of cancer, leads to the down-regulation of the KAI1 gene, which may result in the progression of metastasis.

Myoglobin in myocardial infarction. Results in a coronary-care-unit population.

The purpose of this study was to define the performance characteristics of serum myoglobin determinations in the diagnosis of acute myocardial infarction (MI). Subjects of the study were 118 patients admitted consecutively to the coronary care unit. Daily measurements of serum myoglobin (by radioimmunoassay) were performed. For patients admitted within 24 hours of the onset of symptoms, a serum myoglobin level of 75 ng/ml had a diagnostic sensitivity of 91% and a specificity of 85%. In the same group of patients, the presence of the myocardial isoenzyme of creatine phosphokinase (CK-MB) showed a sensitivity of 94% and a specificity of 89%. Among the 32 patients with MI, the elevation of myoglobin preceded the appearance of CK-MB in 12 (38%), was concomitant with CK-MB appearance in 15 (47%), and followed CK-MB in none. Given the spectrum of patients in this coronary care unit, the addition of the myoglobin assay to the heart profile has increased its sensitivity for the diagnosis of MI. The assay materials are available in kit form, and the test can be performed in the routine radioimmunoassay laboratory. The results are available for reporting four to five hours after venipuncture.

Intracoronary myocardial perfusion imaging: patterns in patients with coronary artery disease.

Myocardial imaging following the intracoronary injection of radiolabeled particles is used to identify transmural scars in patients being evaluated for coronary atherosclerosis. Selective imaging of the microcirculation derived from each major coronary vessel is accomplished using a dual radionuclide technique. This report illustrates the various normal and abnormal imaging patterns encountered in patients with coronary artery disease. The regional myocardial nomenclature proposed by the American Heart Association Council on Cardiovascular Surgery is used. Correlation of the nuclear study with the contrast arteriogram and ventriculogram is essential for identifying both transmural scars and regions of collateral circulation. The procedure is safe and can be performed during routine coronary angiography.

Maximal treadmill exercise testing in the management of the post-myocardial infarction patient.

Treadmill exercise tests were performed on 32 active duty military personnel 9 to 11 months after acute myocardial infarction to enable more objective selection of candidates for return to military service. Treadmill exercise tests were terminated at heart rates averaging 92 percent maximal predicted rate for age, or when chest discomfort with ischemic ECG changes occurred. The incidence of lipid abnormalities, hypertension, and other coronary risk factors did not differ among the groups. However, treadmill exercise tests appeared to identify a high risk group. Treadmill exercise testing in young postmyocardial infarction patients suggests that those with ischemic responses are at high risk of subsequent cardiac complications. Early surgery in this group may be warranted. The more frequently encountered negative response appears to be associated with a benign clinical course and better immediate prognosis.