Cognitive assessment of the medical patient.

Cognitive assessment is the clinical examination of higher mental functioning. A structured and logical approach leads the clinician to identify specific functional deficits and patterns of dysfunction. This allows accurate diagnosis, which is vital to identify treatable disorders and quantify the nature of decline in irreversible conditions. This article defines common terms in use, suggests a logical deductive procedure and discusses screening tools.

Biologic markers in cancer diagnosis and treatment.

We have reviewed several tumor markers that our advocates feel are now clinically useful, involve current assay technology, and are based on already available information. These include, in selected instances, estrogen receptors for breast cancer, thyrocalcitonin for medullary cancer of the thyroid, prostatic acid phosphatase for cancer of the prostate, alpha-fetoprotein for hepatocellular cancer, and carcinoembryonic antigen for monitoring colon cancer. We have considered the potential use of measurement of serum proteases and protein degradation products due to their activity as possible future areas of development, and we have explored measurement of tissue aryl hydrocarbon hydroxylase to identify populations at risk of cancer resulting from chemical carcinogenesis. It is clear that the study of tumor markers is already improving patient care in some specific areas and offers exciting potential for the future.

Covalent structure of human haptoglobin: a serine protease homolog.

The complete amino acid sequences and the disulfide arrangements of the two chains of human haptoglobin 1-1 were established. The alpha 1 and beta chains of haptoglobin contain 83 and 245 residues, respectively. Comparison of the primary structure of haptoglobin with that of the chymotrypsinogen family of serine proteases revealed a significant degree of chemical similarity. The probability was less than 10(-5) that the chemical similarity of the beta chain of haptoglobin to the proteases was due to chance. The amino acid sequence of the beta chain of haptoglobin is 29--33% identical to bovine trypsin, bovine chymotrypsin, porcine elastase, human thrombin, or human plasmin. Comparison of haptoglobin alpha 1 chain to activation peptide regions of the zymogens revealed an identity of 25% to the fifth "kringle" region of the activation peptide of plasminogen. The probability was less than 0.014 that this similarity was due to chance. These results strongly indicate haptoglobin to be a homolog of the chymotrypsinogen family of serine proteases. Alignment of the beta-chain sequence of haptoglobin to the serine proteases is remarkably consistent except for an insertion of 16 residues in the region corresponding to the methionyl loop of the serine proteases. The active-site residues typical of the serine proteases, histidine-57 and serine-195, are replaced in haptoglobin by lysine and alanine, respectively; however, aspartic acid-102 and the trypsin specificity, residue, aspartic acid-189, do occur in haptoglobin. Haptoglobin and the serine proteases represent a striking example of homologous proteins with different biological functions.

Patterns of benzo[alpha]pyrene metabolism in normal human pulmonary alveolar macrophages.

Pulmonary alveolar macrophages (PAMs) obtained by bronchopulmonary lavage from 6 normal non-smoking volunteers were incubated with [3H]-benzo[alpha]pyrene to ascertain the normal metabolism and conjugation of polycyclic aromatic hydrocarbons. Through the use of a crude glucuronidase preparation, both glucuronic acid and sulfate conjugates were examined. Phenols and quinones were identified by high-pressure liquid chromatography as the principal free metabolites formed during 1 h incubation with benzanthracene induced PAMs. In addition, phenols and quinones were major substrates utilized by these cells for conjugation during the incubation period. The ranges of benzo[alpha]pyrene metabolites produced by PAMs from non-smokers were compiled and the variation in production as well as detoxification of proximate carcinogenic benzo[alpha]pyrene metabolites are presented.

Selenium effects on the carcinogenicity and metabolism of 2-acetylaminofluorene.

Addition of 4 ppm Se to the drinking water of male albino rats fed diets containing 0.03% 2-acetylaminofluorene (AAF) provided protection against hepatic damage and also resulted in at least 50% reduction in liver tumor incidence. An in vitro assay system utilizing microsomes from Se supplemented or non-supplemented 3-methylcholanthrene (MC) induced rats was used to determine the effect of oral Se intake on the metabolism of AAF. Oral Se administration led to an increase in ring hydroxylation and a decrease in N-hydroxylation. Addition of Se to the microsomal assay system increased 3-OH AAF formation and decreased N-OH AAF formation, thus shifting the balance of metabolism toward detoxification pathways.

Aryl hydrocarbon hydroxylase induction in mitogen-stimulated lymphocytes by benzanthracene or cigarette tars adsorbed to asbestos fibers.

Human mitogen-stimulated lymphocytes, cultured in the presence of amosite asbestos (AS), demonstrated a slight increase in aryl hydrocarbon hydroxylase (AHH) activity compared with non-induced (control) cultures (P = 0.005). A much greater increase in enzyme activity occurred following addition of the inducers benzanthracene (BA) or cigarette tars (CT) to cell cultures (P less than 0.001 in both instances). Significant enzyme induction also occurred when AS fibers were first preincubated with CT or BA, washed with acetone, then added to lymphocyte cultures (P less than 0.003 in all instances). This increase in AHH activity was not as great, however, as the induction observed when BA or CT was added to cell cultures. No further increase in enzyme activity was noted when AS and CT or AS and BA were simultaneously added to culture lymphocytes (P greater than 0.070 in all instances). The results demonstrate that polycyclic aromatic hydrocarbons (PAH), such as BA and other components of CT, are adsorbed and transported by amosite AS particles. These AS-PAH complexes are capable of inducing AHH in cultured human lymphocytes.